A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults

  • Darren ER Warburton1, 2Email author,

    Affiliated with

    • Sarah Charlesworth1, 2,

      Affiliated with

      • Adam Ivey1, 2,

        Affiliated with

        • Lindsay Nettlefold1, 2 and

          Affiliated with

          • Shannon SD Bredin3

            Affiliated with

            International Journal of Behavioral Nutrition and Physical Activity20107:39

            DOI: 10.1186/1479-5868-7-39

            Received: 24 July 2009

            Accepted: 11 May 2010

            Published: 11 May 2010

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            Abstract

            This systematic review examines critically the scientific basis for Canada's Physical Activity Guide for Healthy Active Living for adults. Particular reference is given to the dose-response relationship between physical activity and premature all-cause mortality and seven chronic diseases (cardiovascular disease, stroke, hypertension, colon cancer, breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis). The strength of the relationship between physical activity and specific health outcomes is evaluated critically. Literature was obtained through searching electronic databases (e.g., MEDLINE, EMBASE), cross-referencing, and through the authors' knowledge of the area. For inclusion in our systematic review articles must have at least 3 levels of physical activity and the concomitant risk for each chronic disease. The quality of included studies was appraised using a modified Downs and Black tool. Through this search we identified a total of 254 articles that met the eligibility criteria related to premature all-cause mortality (N = 70), cardiovascular disease (N = 49), stroke (N = 25), hypertension (N = 12), colon cancer (N = 33), breast cancer (N = 43), type 2 diabetes (N = 20), and osteoporosis (N = 2). Overall, the current literature supports clearly the dose-response relationship between physical activity and the seven chronic conditions identified. Moreover, higher levels of physical activity reduce the risk for premature all-cause mortality. The current Canadian guidelines appear to be appropriate to reduce the risk for the seven chronic conditions identified above and all-cause mortality.

            Introduction

            There is considerable literature supporting the importance of habitual physical activity in the primary and secondary prevention of varied chronic conditions [116]. Routine physical activity is thought to be of benefit for over 25 chronic conditions [17]. Seven chronic diseases in particular have been associated with a physically inactive lifestyle including coronary artery disease, stroke, hypertension, colon cancer, breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis [1820].

            Canada has played a leading role in the development of physical activity guidelines for individuals across the lifespan. This includes the development (in 1998) of "Canada's Physical Activity Guide to Healthy Active Living" for adults between the ages of 20 and 55 yr [21], which was followed by "Canada's Physical Activity Guide to Healthy Active Living for Older Adults" [22], and "Canada's Physical Activity Guide to Healthy Active Living for Children and Youth" [23]. The adult guidelines (which are now approximately 10 years old) state generally that 20-55 yr adults should accumulate 60 min of daily physical activity or 30 min of moderate to vigorous exercise on at least 4 days a week [18, 19].

            We reported recently that Canada's adult guidelines were consistent with other international guidelines and were supported by a compelling body of literature [18, 19]. We revealed strong evidence that routine physical activity was effective in the primary prevention of cardiovascular disease, stroke, hypertension, breast cancer, colon cancer, type 2 diabetes and osteoporosis. Moreover, physical activity appears to play an important role in the prevention of obesity and obesity-related co-morbidities. However, implicit in the adult guidelines is the belief that there is a dose-response relationship between physical activity and the associated health benefits. Moreover, a central belief in these guidelines and most international physical activity guidelines is that the dose-response relationship is curvilinear with the greatest health benefits seen in physically inactive individuals who become "more physically active." In fact, a consistent pattern (shown in Figure 1) has been hypothesized, wherein there are marked changes in health status with relatively minor increments in physical activity/fitness in individuals that are the least active/fit. Generally, the health benefits have been thought to level off at the upper end of the physical activity/fitness continuum (Figure 1). However, recent work (such as that provided by Gledhill and Jamnik in the Canadian Physical Activity and Lifestyle Approach) has speculated that there are likely multiple dose-response curves for various endpoints [24].
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig1_HTML.jpg
            Figure 1

            Theoretical relationship between the risk for chronic disease and physical activity/fitness.

            The primary purpose of this systematic review was to examine critically the current literature to determine whether or not a dose-response relationship exists between habitual physical activity and chronic disease. In particular, we sought to determine whether the key messaging "Every little bit counts, but more is even better - everyone can do it!" of the adult physical activity guidelines is supported by a strong body of evidence.

            Due to the breadth of literature, we have chosen to focus on the relationship between physical activity and all-cause mortality, and the seven chronic conditions that are thought to be reduced greatly with habitual physical activity (i.e., cardiovascular disease (excluding stroke), stroke, hypertension, colon cancer, breast cancer, type 2 diabetes and osteoporosis) (see Table 1). Owing to the nature of the physical activity guidelines, the emphasis of this paper was on primary prevention, despite the clear evidence that routine physical activity is also an effective secondary preventative strategy against many chronic conditions [16, 18, 19]. Accordingly, our primary objectives were to examine the evidence for a dose-response relationship between: 1) physical activity and all-cause mortality, and 2) physical activity and incidence of the following chronic conditions (cardiovascular disease (except stroke), stroke, hypertension, type 2 diabetes, colon cancer, breast cancer, and osteoporosis.
            Table 1

            Relative risks (RR) and population attributable risks (PAR%) for physical inactivity in Canada, Australia, and the USA.

             

            Canada

            Australia

            USA

            Disease

            RR

            PAR%

            RR

            PAR%

            RR

            PAR%

            CHD

            1.45

            19.4

            1.5

            18

            2.0

            22

            Stroke

            1.60

            24.3

            2.0

            16

            na

            Na

            Hypertension

            1.30

            13.8

            na

            na

            1.5

            12

            Colon Cancer

            1.41

            18.0

            1.5

            19

            2.0

            22

            Breast Cancer

            1.31

            14.2

            1.1

            9

            1.2

            5

            Type 2 Diabetes

            1.50

            21.1

            1.3

            13

            1.5

            12

            Osteoporosis

            1.59

            24.0

            1.4*

            18*

            2.0

            18*

            Source: Canadian Data [20]; Australian Data [161]; US Data: [162]. *Evaluated the incidence of falls/fractures.

            Methods

            Criteria for considering studies for this review

            Our research team utilized a rigorous, systematic, and evidence-based approach to examine critically the levels of evidence on physical activity and the risk for premature mortality and chronic disease. Any studies that evaluated the relationship between at least three different levels of physical activity and mortality or incidence of chronic disease were eligible for inclusion. Therefore, excluded studies included those that examined only the most active versus least active populations (e.g., sedentary/inactive vs. physically active). Any form of physical activity/exercise measurement (e.g., self-report, pedometer, accelerometer, maximal aerobic power (VO2 max)) was eligible for inclusion. The key outcomes were mortality and incidence of chronic disease. Only published, English language studies examining adults (e.g., 19-65 yr) were included. Participants must have previously been healthy (asymptomatic) adults without established chronic disease. There was no restriction according to study design.

            To examine the relative risk reductions associated with physical activity, we calculated the mean and median risk reductions across studies focusing on the highest level versus the lowest level of physical activity/fitness. For each study we also determined whether or not a dose-response relationship was present (i.e., reflecting a progressive decrease in the risk with increasing physical activity/fitness levels).

            Search strategy

            Literature searches were conducted in the following electronic bibliographical databases:

            • MEDLINE (1950-March 2008, OVID Interface);

            • EMBASE (1980- March 2008, OVID Interface),

            • CINAHL (1982- March 2008, OVID Interface);

            • PsycINFO (1840- March 2008, Scholars Portal Interface);

            • Cochrane Library (-March 2008),

            • SPORTDiscus (-March 2008).

            The Medical Subject Headings (MeSH) were kept broad. See tables 2, 3, 4, 5, 6, 7, 8 and 9 for the complete search strategy and keywords used. The electronic search strategies were created and carried out by researchers experienced with systematic reviews of the literature (DW and LN). The citations and applicable electronic versions of the article (where available) were downloaded to an online research management system (RefWorks, Bethesda, Maryland, USA).
            Table 2

            Results of the MEDLINE literature search regarding all-cause mortality.

            #

            Searches (28 Feb 2008)

            Results

            1

            exp Physical Fitness/

            15236

            2

            Motor Activity/

            49721

            3

            exp Physical Endurance/

            15383

            4

            exp Exercise/

            57742

            5

            exp Exertion/

            88903

            6

            exp Sports/

            71887

            7

            exp exercise therapy/

            17231

            8

            exp exercise tolerance/

            4192

            9

            exp health behaviour/

            59409

            10

            leisure time physical activity.mp

            996

            11

            occupational physical activity.mp

            190

            12

            exp Pliability/

            2279

            13

            exp Muscle Strength/

            5717

            14

            musc$ power.mp

            965

            15

            exp Back/

            12821

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291635

            17

            dose-response.mp

            321066

            18

            intensity.mp

            142881

            19

            volume.mp

            298471

            20

            exp Energy Metabolism/

            206808

            21

            exp oxygen consumption/

            83352

            22

            exp time factors/

            763712

            23

            17 or 18 or 19 or 20 or 21 or 22

            1651633

            24

            16 and 23

            67698

            25

            exp Mortality/

            190058

            26

            all cause mortality.mp

            4618

            27

            25 or 26

            192720

            28

            24 and 27

            421

            29

            limit 28 to (english and humans and "all adult (19 plus years)

            279

            Table 3

            Results of the MEDLINE literature search regarding cardiovascular disease.

            Search #

            Searches (3 Mar 2008)

            Results

            1

            exp Physical Fitness/

            15244

            2

            Motor Activity/

            49751

            3

            exp Physical Endurance/

            15408

            4

            exp Exercise/

            57806

            5

            exp Exertion/

            88967

            6

            exp Sports/

            71931

            7

            exp exercise therapy/

            17243

            8

            exp exercise tolerance/

            4205

            9

            exp health behaviour/

            59467

            10

            leisure time physical activity.mp

            998

            11

            occupational physical activity.mp

            191

            12

            exp Pliability/

            2289

            13

            exp Muscle Strength/

            5731

            14

            musc$ power.mp

            965

            15

            exp Back/

            12822

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291817

            17

            dose-response.mp

            321198

            18

            intensity.mp

            142955

            19

            volume.mp

            298620

            20

            exp Energy Metabolism/

            206886

            21

            exp oxygen consumption/

            83387

            22

            exp time factors/

            764091

            23

            17 or 18 or 19 or 20 or 21 or 22

            1652372

            24

            16 and 23

            67760

            25

            exp Cardiovascular Diseases/

            1411730

            26

            exp Heart diseases/

            675083

            27

            exp Myocardial infarction/

            116070

            28

            exp Death, Sudden Cardiac/

            6772

            29

            exp Coronary Artery Disease/

            18137

            30

            exp Coronary Disease/

            144236

            31

            exp Vascular Diseases

            1018275

            32

            25 or 26 or 27 or 28 or 29 or 30 or 31

            1411730

            33

            24 and 32

            9603

            34

            limit 33 to (english language and humans and "all adult (19 plus years)")

            5544

            Table 4

            Results of the MEDLINE literature search regarding stroke.

            Search #

            Searches (29 Feb 2008)

            Results

            1

            exp Physical Fitness/

            15241

            2

            Motor Activity/

            49744

            3

            exp Physical Endurance/

            15387

            4

            exp Exercise/

            57764

            5

            exp Exertion/

            88921

            6

            exp Sports/

            71907

            7

            exp exercise therapy/

            17237

            8

            exp exercise tolerance/

            4196

            9

            exp health behaviour/

            59430

            10

            leisure time physical activity.mp

            996

            11

            occupational physical activity.mp

            190

            12

            exp Pliability/

            2288

            13

            exp Muscle Strength/

            5720

            14

            musc$ power.mp

            965

            15

            exp Back/

            12821

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291718

            17

            dose-response.mp

            321133

            18

            intensity.mp

            142919

            19

            volume.mp

            298526

            20

            exp Energy Metabolism/

            206837

            21

            exp oxygen consumption/

            83359

            22

            exp time factors/

            763871

            23

            17 or 18 or 19 or 20 or 21 or 22

            1651958

            24

            16 and 23

            67720

            25

            exp Stroke/

            45243

            26

            exp Cerebrovascular Disorders/

            196243

            27

            exp Brain Ischemia/

            58943

            28

            exp Brain Infarction/ or exp Cerebral Infarction

            21357

            29

            exp Infarction, Middle Cerebral Artery/ or exp Intracranial Aneurysm/ or exp Subarachnoid

            46725

            30

            Hemorrhage/ or exp Cerebral Hemorrhage/exp Ischemic Attack, Transient/

            14753

            31

            25 or 26 or 27 or 28 or 29 or 30

            196243

            32

            24 and 31

            692

            33

            limit 32 to (english language and humans and "all adult (19 plus years)")

            291

            Table 5

            Results of the MEDLINE literature search regarding hypertension.

            Search #

            Searches (3 Mar 2008)

            Results

            1

            exp Physical Fitness/

            15244

            2

            Motor Activity/

            49751

            3

            exp Physical Endurance/

            15408

            4

            exp Exercise/

            57806

            5

            exp Exertion/

            88967

            6

            exp Sports/

            71931

            7

            exp exercise therapy/

            17243

            8

            exp exercise tolerance/

            4205

            9

            exp health behaviour/

            59467

            10

            leisure time physical activity.mp

            998

            11

            occupational physical activity.mp

            191

            12

            exp Pliability/

            2289

            13

            exp Muscle Strength/

            5731

            14

            musc$ power.mp

            965

            15

            exp Back/

            12822

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291817

            17

            dose-response.mp

            3211987

            18

            intensity.mp

            142955

            19

            volume.mp

            298620

            20

            exp Energy Metabolism/

            206886

            21

            exp oxygen consumption/

            83387

            22

            exp time factors/

            764091

            23

            17 or 18 or 19 or 20 or 21 or 22

            1652372

            24

            exp Hypertension/

            168466

            25

            exp Blood Pressure/

            205571

            26

            exp Blood Pressure Determination/ or exp Blood Pressure Monitoring, Ambulatory/ or exp Blood

            18244

            27

            Pressure Monitors/24 or 25 or 26

            336025

            28

            16 and 23 and 27

            5647

            29

            limit 28 to (english language and humans and "all adult (19 plus years)")

            3642

            Table 6

            Results of the MEDLINE literature search regarding colon cancer.

            Search #

            Searches (3 Mar 2008)

            Results

            1

            exp Physical Fitness/

            15244

            2

            Motor Activity/

            49751

            3

            exp Physical Endurance/

            15408

            4

            exp Exercise/

            57806

            5

            exp Exertion/

            88967

            6

            exp Sports/

            71931

            7

            exp exercise therapy/

            17243

            8

            exp exercise tolerance/

            4205

            9

            exp health behaviour/

            59467

            10

            leisure time physical activity.mp

            998

            11

            occupational physical activity.mp

            191

            12

            exp Pliability/

            2289

            13

            exp Muscle Strength/

            5731

            14

            musc$ power.mp

            965

            15

            exp Back/

            12822

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291817

            17

            dose-response.mp

            321198

            18

            intensity.mp

            142955

            19

            volume.mp

            298620

            20

            exp Energy Metabolism/

            206886

            21

            exp oxygen consumption/

            83387

            22

            exp time factors/

            764091

            23

            17 or 18 or 19 or 20 or 21 or 22

            1652372

            24

            exp Colonic Neoplams/

            51780

            25

            exp Rectal Neoplasms/

            28011

            26

            exp Colorectal Neoplasms/

            99982

            27

            exp Colorectal Neoplasms/, Hereditary Nonpolyposis/ or exp Intestinal Neoplasms.

            117563

            28

            24 or 25 or 26 or 27

            117563

            29

            16 and 23 and 28

            108

            30

            limit 29 to (53nglish language and humans and "all adult (19 plus years)")

            77

            Table 7

            Results of the MEDLINE literature search regarding breast cancer.

            Search #

            Searches (28 Feb 2008)

            Results

            1

            exp Physical Fitness/

            15236

            2

            Motor Activity/

            49721

            3

            exp Physical Endurance/

            15383

            4

            exp Exercise/

            57742

            5

            exp Exertion/

            88903

            6

            exp Sports/

            71887

            7

            exp exercise therapy/

            17231

            8

            exp exercise tolerance/

            4192

            9

            exp health behaviour/

            59409

            10

            leisure time physical activity.mp

            996

            11

            occupational physical activity.mp

            190

            12

            exp Pliability/

            2279

            13

            exp Muscle Strength/

            5717

            14

            musc$ power.mp

            965

            15

            exp Back/

            12821

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291635

            17

            dose-response.mp

            321066

            18

            intensity.mp

            142881

            19

            volume.mp

            298471

            20

            exp Energy Metabolism/

            206808

            21

            exp oxygen consumption/

            83352

            22

            exp time factors/

            763712

            23

            17 or 18 or 19 or 20 or 21 or 22

            1651633

            24

            exp Breast Neoplasms/

            149817

            25

            16 and 23 and 24

            296

            26

            limit 25 to (54 nglish language and humans and "all adult (19 plus years)"

            216

            Table 8

            Results of the MEDLINE literature search regarding type 2 diabetes.

            Search #

            Searches (29 Feb 2008)

            Results

            1

            exp Physical Fitness/

            15241

            2

            Motor Activity/

            49744

            3

            exp Physical Endurance/

            15387

            4

            exp Exercise/

            57764

            5

            exp Exertion/

            88921

            6

            exp Sports/

            71907

            7

            exp exercise therapy/

            17237

            8

            exp exercise tolerance/

            4196

            9

            exp health behaviour/

            59430

            10

            leisure time physical activity.mp

            996

            11

            occupational physical activity.mp

            190

            12

            exp Pliability/

            2288

            13

            exp Muscle Strength/

            5720

            14

            musc$ power.mp

            965

            15

            exp Back/

            12821

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291718

            17

            dose-response.mp

            321133

            18

            intensity.mp

            142919

            19

            volume.mp

            298526

            20

            exp Energy Metabolism/

            206837

            21

            exp oxygen consumption/

            83359

            22

            exp time factors/

            763871

            23

            17 or 18 or 19 or 20 or 21 or 22

            1651958

            24

            16 and 23

            67720

            25

            exp Blood Glucose/or exp Diabetes Mellitus, Type 2/

            132583

            26

            exp Hyperglycemia/

            16214

            27

            exp Glucose Intolerance/ or exp Glucose Tolerance Test/

            24986

            28

            exp Hyperinsulinism/

            30490

            29

            25 or 26 or 27 or 28

            165157

            30

            29 and 24

            3006

            31

            Limit 30 to (english language and humans and "all adult (19 plus years)")

            1985

            Table 9

            Results of the MEDLINE literature search regarding osteoporosis.

            Search #

            Searches (29 feb 2008)

            Results

            1

            exp Physical Fitness/

            15241

            2

            Motor Activity/

            49744

            3

            exp Physical Endurance/

            15387

            4

            exp Exercise/

            57764

            5

            exp Exertion/

            88921

            6

            exp Sports/

            71907

            7

            exp exercise therapy/

            17237

            8

            exp exercise tolerance/

            4196

            9

            exp health behaviour/

            59430

            10

            leisure time physical activity.mp

            996

            11

            occupational physical activity.mp

            190

            12

            exp Pliability/

            2288

            13

            exp Muscle Strength/

            5720

            14

            musc$ power.mp

            965

            15

            exp Back/

            12821

            16

            1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

            291718

            17

            dose-response.mp

            321133

            18

            intensity.mp

            142919

            19

            volume.mp

            298526

            20

            exp Energy Metabolism/

            206837

            21

            exp oxygen consumption/

            83359

            22

            exp time factors/

            763871

            23

            17 or 18 or 19 or 20 or 21 or 22

            1651958

            24

            exp Osteoporosis, Postmenopausal/ or exp Osteoporosis/

            31532

            25

            exp Fractures, Bone/ or exp Bone Density/

            125269

            26

            exp Bone Diseases/ or exp Bone Diseases, Metabolic/

            308084

            27

            exp "Bone and bones"/

            369634

            28

            exp Tensile Strength/

            12050

            29

            exp Compressive Strength

            2838

            30

            24 or 25 or 26 or 27 or 28 or 29

            642158

            31

            16 and 23 and 30

            2138

            32

            limit 31 to (english language and humans and "all adult (19 plus years)")

            1193

            Screening

            Two reviewers (LN and SC) screened independently the title and abstract of the citations to identify potential articles for inclusion. Duplicate citations were removed. The reviewers were not blinded to the authors or journals. Biographies of key studies and reviews in the field were also cross-referenced for further articles. For those articles that appeared relevant, the full text was obtained and data was extracted using a common template. In cases of disagreement, discussion with a third reviewer (DW) was used to achieve consensus. Full (100%) consensus was achieved. All studies that were excluded during the citation and full-article screening processes were recorded along with the reasons for exclusion.

            Data Extraction

            Two reviewers (LN and SC) completed standardized data extraction forms, which were verified by two other reviewers (DW and SB). We extracted information regarding the study design, the country where the study was conducted, the participant characteristics, the sample size, the objectives of the study, the methodologies employed, the major outcomes (i.e., mortality, incidence of chronic disease, physical activity levels/classifications), and the comments and conclusions made based on the findings of the study. The reviewers were not blinded to the journal or the author names when extracting information from the articles.

            Level of Evidence

            The approach used to establish the level and grade of evidence was consistent with that used during creation of the "Canadian clinical practice guidelines on the management and prevention of obesity in adults and children" [25]. The level of evidence provides information regarding the strength of the evidence in favour of physical activity/exercise in the primary prevention of premature mortality and the seven chronic diseases of primary interest. This evaluation process is based on a pre-defined and objective criteria (see Table 10).
            Table 10

            The levels and grade of evidence scaling criteria applied to the articles.

            Level of Evidence

            Criteria

            Level 1

               Randomized control trials without important limitations

            Level 2

               • Randomized control trials with important limitations

             

               • Observational studies (non-randomized clinical trials or cohort studies) with overwhelming evidence

            Level 3

            Other observational studies (prospective cohort studies, case-control studies, case series)

            Level 4

            Inadequate or no data in population of interest

             

            Anecdotal evidence or clinical experience

            Grade of Evidence

            Criteria

            Grade A

            Strong recommendation (action can apply to most individuals in most circumstances)

             

               • Benefits clearly outweigh risks (or vice-versa)

             

               • Evidence is at Level 1, 2, or 3

            Grade B

            Weak recommendation (action may differ depending on individual's characteristics or other circumstances)

             

               • Unclear if benefits outweigh risks

             

               • Evidence is at Level 1, 2, or 3

            Grade C

            Consensus recommendation (alternative actions may be equally reasonable)

             

               • Unclear if benefits outweigh risks

             

               • Evidence is at Level 3 or 4

            The grade for each article provides information regarding whether physical activity is effective in the primary prevention of the varied conditions evaluated (Table 10). Where applicable this grade informs the reader about the potential risk of the physical activity. A study that receives the highest grading would indicate that the benefits clearly outweigh the risks and receive a strong recommendation.

            Quality Assessment

            The quality of each study was also established using the procedures of Gorber et al. [26]. Owing to the fact that only observational study designs were included in our systematic review, we used the Downs and Black [27] scale to assess the quality of non-randomized investigations. Similar to the work of Prince et al. [28] we chose to include the most relevant components of the scoring tool. Therefore, a modified version of the Downs and Black checklist was used with the final checklist consisting of 15 items with a maximum score of 15 points. Higher points reflected a superior quality of investigation.

            Results

            Physical Inactivity and All-Cause Mortality

            A total of 2040 citations were identified during the electronic database search (Figure 2). Of these citations, 288 were identified in MEDLINE, 222 in EMBASE, 496 in Cochrane, and 1034 in the CINAHL/SportDiscus/PsychInfo search. A total of 167 duplicates were found, leaving a total of 1873 unique citations. A total of 1696 articles were excluded after scanning, leaving a total of 177 articles for full review. From these articles 130 were excluded after full review leaving 47 articles for inclusion in the systematic review. An additional 23 articles were added to the review based on the authors' knowledge of the area. The reasons for exclusion included review articles (n = 26), commentary (n = 10), did not report 3 levels of physical activity (n = 24), no objective measure of physical activity (n = 2), report (n = 15), not a formal study (n = 11), not related to all-cause mortality (n = 27), the participants were too young (n = 1), not able to retrieve articles (n = 7), and other (n = 7). Therefore, a total of 70 articles were included in the systematic review of the literature regarding the relationship between physical activity and premature mortality.
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig2_HTML.jpg
            Figure 2

            Results of the Literature Search for All-Cause Mortality.

            The majority of the studies included in our systematic review were prospective cohort investigations (Table 11). These studies involved a total of 1,525,377 participants; averaging 21,791 participants per study (range 302-252,925). There were a total of 111,125 reported cases of premature all-cause mortality (ranging per study from 43-10,952). The total length of study follow-up for the prospective cohort studies averaged 11.1 yr (ranging from 0.5-28 yr). The articles were published over a 22 yr period ranging from 1985 to 2007. These studies involved large samples of men and women from regions throughout the world.
            Table 11

            Studies examining the relationship between physical activity and all-cause mortality.

            Publication Country Study Design Quality Score

            Objective

            Population

            Methods

            Outcome

            Comments and Conclusions

            Blair et al 1989 [7]

            To study physical fitness (PF) and risk of all-cause mortality in men and women.

            • n = 13,344 (10,224 men; 3,120 women)

            Baseline and 8 year follow-up

               • 283 deaths

            Low levels of PF increase the risk for premature mortality.

              

            • Sex: Men and women

             

            Adjusted risk ratio (RR), 95% confidence interval (CI)

             

            USA

             

            • Age: 20->60 years (yr)

            PF assessment: Maximal treadmill exercise test.

              

            Prospective cohort

             

            • Characteristics: Participants were given a preventative Medicine examination including maximal treadmill exercise test

            Fitness categorized into quintiles:

            Men

             

            D & B score = 12

              

            Q1 = least fit

               • Q1 = 3.44 (2.05-5.77)

             
               

            Q2

               • Q2 = 1.37 (0.76-2.50)

             
               

            Q3

               • Q3 = 1.46 (0.81-2.63)

             
               

            Q4

               • Q4 = 1.17 (0.63-2.17)

             
               

            Q5 = most fit

               • Q5 = 1.00 (referent)

             
                

            Women

             
                

               • Q1 = 4.65 (2.22-9.75)

             
                

               • Q2 = 2.42 (1.09-5.37)

             
                

               • Q3 = 1.43 (0.60-3.44)

             
                

               • Q4 = 0.76 (0.27-2.11)

             
                

               • Q5 = 1.00 (referent)

             

            Myers et al 2004 [32]

            To determine the effects of PF and physical activity (PA) on all-cause mortality.

            • n = 6,213

            Baseline and mean 5.5 ± 2.0 year follow-Up

               • 1,256 deaths

            Being fit or active is associated with >50% reductions in mortality risk.

              

            • Sex: Men

               

            USA

             

            • Age: Mean 59.0 ± 11.2 yr

             

            PF Level hazard ratio (HR) (95% CI)

             
              

            • Characteristics: Men referred for exercise testing

            PF assessment: Treadmill test to measure VO2 peak

               • G1 = 1.00 (referent)

            PF predicted mortality more strongly than PA.

            Prospective cohort

               

               • G2 = 0.59 (0.52-0.68)

             
                

               • G3 = 0.46 (0.39-0.55)

             
                

               • G4 = 0.28 (0.23-0.34)

            Increasing PA (by 1000 kcal/wk or 1 MET) confers a mortality benefit of 20%.

            D & B score = 12

              

            PA assessment: Self reported PA divided into 4 groups

              
                

            PA Level HR (95% CI)

             
               

            G1 = Lowest level

               • G1 = 1.00 (referent)

             
               

            G2

               • G2 = 0.63 (0.36-1.10)

             
               

            G3

               • G3 = 0.42 (0.23-0.78)

             
               

            G4 = Highest level

               • G4 = 0.38 (0.19-0.73)

             

            Blair et al 1995 [36]

            To evaluate the relationship between changes in PF and risk of mortality in men.

            • n = 9,777

            4.9 year mean follow-up

               • 223 deaths

            Men who maintained or increased adequate PF had a reduced risk for all-cause mortality than individuals who were consistently unfit.

              

            • Sex: Men

               
              

            • Age: 20-82 yr

             

            RR (95% CI)

             

            USA

             

            • Characteristics: Participants were given a preventative medicine examination including maximal treadmill exercise test

            PF assessment: Maximal exercise test at baseline and follow-up

               • G1 = 1.00 (referent)

             

            Prospective cohort

               

               • G2 = 0.56 (0.41-0.75)

             
                

               • G3 = 0.52 (0.38-0.70)

             
                

               • G4 = 0.33 (0.23-0.47)

             

            D & B score = 13

              

            Groups based on changes in PF

              
               

            G1 = unfit to unfit

              
               

            G2 = unfit to fit

              
               

            G3 = fit to unfit

              
               

            G4 = fit to fit

              

            Bijnen et al 1999 [37]

            To examine the association of PA at baseline and 5 years

            • n = 472

            1985 and 1990

               • 118 deaths

            Recent levels of PA were more important for mortality risk than PA 5 years previously.

              

            • Sex: Men

               
              

            • Age: >65 yr

            PA assessment: Questionnaire, divided into tertiles: Lowest Middle Highest

            Multivariate adjusted RR (95% CI)

             

            Netherlands

            previously with all- cause mortality risk in a cohort of elderly Dutch men.

            • Characteristics: Mostly independently living elders (~95%)

             

            PA in 1985: Lowest tertile = 1.00 (referent) Middle tertile

             

            Retrospective cohort

             

            • Zutphen Elderly Study

             

               • Total activity = 1.25 (0.79- 1.99)

            Becoming or remaining sedentary increased the mortality risk.

            D & B score = 12

               

               • Walking = 0.97 (0.60-1.57)

             
                

               • Bike = 0.97 (0.59-1.57)

             
                

               • Gardening = 0.66 (0.39-1.10)

             
                

               • Other = 1.08 (0.66-1.78)

             
                

               • Heavy activity = 0.73 (0.45-1.17)

             
                

               • Non heavy activity = 0.89 (0.57-1.40)

             
                

            Highest tertile

             
                

               • Total activity = 1.25 (0.73-2.12)

             
                

               • Walking = 0.94 (0.58-1.55)

             
                

               • Bike = 1.07 (0.61-1.88)

             
                

               • Gardening = 0.77 (0.42-1.39)

             
                

               • Other = 1.24 (0.74-2.07)

             
                

               • Heavy activity = 0.76 (0.44-1.32)

             
                

               • Non heavy activity = 0.94 (0.58-1.53)

             
                

            PA in 1990:

             
                

            Lowest tertile = 1.00 (referent)

             
                

            Middle tertile

             
                

               • Total activity = 0.56 (0.35-0.89)

             
                

               • Walking = 0.82 (0.51-1.32)

             
                

               • Bike = 0.49 (0.29-0.82)

             
                

               • Gardening = 1.67 (1.00-2.79)

             
                

               • Other = 0.93 (0.53-1.65)

             
                

               • Heavy activity = 1.19 (0.73-1.92)

             
                

               • Non heavy activity = 0.61 (0.38-0.99)

             
                

            Highest tertile

             
                

               • Total activity = 0.44 (0.25-0.80)

             
                

               • Walking = 1.17 (0.70-1.96)

             
                

               • Bike = 0.43 (0.23-0.80)

             
                

               • Gardening = 1.03 (0.55-1.94)

             
                

               • Other = 0.74 (0.44-1.23)

             
                

               • Heavy activity = 0.72 (0.40-1.31)

             
                

               • Non heavy activity = 0.65 (0.40-1.05)

             

            Gregg et al 2003 [39]

            To examine the relationship of changes in PA and mortality among older women.

            • n = 9,518

            Baseline (1986-1988) and median 10.6 year follow-up (1992-1994)

               • 2,218 deaths

            Increasing and maintaining PA levels could lengthen life for older women but appears to provide less benefit for women aged at least 75 years and those with poor health status.

              

            • Sex: Women

            PA Assessment: Questionnaire, divided into quintiles of PA (kcal/wk)

              
              

            • Age: ≥ 65 yr

             

            Multivariate adjusted HRR

             

            USA

             

            • Characteristics: White community dwelling participants from 4 US research centres

             

            (95% CI): Quintiles of total

             
               

            Q1= <163

            PA

             

            Prospective cohort

              

            Q2 = 163-503

               • Q1 = 1.00 (referent)

             
               

            Q3 = 504-1045

               • Q2 = 0.73 (0.64-0.82)

             
               

            Q4 = 1046-1906

               • Q3 = 0.77 (0.68-0.87)

             

            D & B score = 13

              

            Q5 = ≥ 1907

               • Q4 = 0.62 (0.54-0.71)

             
                

               • Q5 = 0.68 (0.59-0.78)

             
                

            Walking HRR (95% CI)

             
                

               • Q1 = 1.00 (referent)

             
               

            Quintiles of walking(kcal/wk)

               • Q2 = 0.91 (0.81-1.02)

             
               

            Q1 = <70

               • Q3 = 0.78 (0.68-0.88)

             
               

            Q2 = 70-186

               • Q4 = 0.71 (0.63-0.82)

             
               

            Q3 = 187-419

               • Q5 = 0.71 (0.62-0.82)

             
               

            Q4 = 420-897

              
               

            Q5 = 898

              
                

            Multivariate adjusted HRR (95% CI)

             
                

            Change in activity level: Sedentary at baseline

             
                

               • Staying sedentary = 1.00 (referent)

             
                

               • Became active = 0.52 (0.40-0.69)

             
                

            Mod / high active at baseline

             
                

               • Became sedentary = 0.92 (0.77-1.09)

             
                

               • Stayed active = 0.68 (0.56-0.82)

             

            Wannamethee et al 1998 [40]

            To study the relationship between heart rate, PA and all- cause mortality.

            • n = 5,934

            Baseline (1978-1980) and 12-14 year follow-up

               • 219 deaths

            Maintaining or taking up light or moderate PA reduces mortality in older men.

              

            • Sex: Men

               
              

            • Age: Mean 63 yr

             

            Multivariate adjusted RR (95% CI),

             

            UK

             

            • Characteristics: Healthy, sedentary(4,311 were considered "healthy" in 1992)

            PA assessment: Questionnaire, split into groups

            PA

             

            Prospective cohort

             

            • The British Regional Heart Study

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.61 (0.43-0.86)

             
                

               • G3 = 0.50 (0.31-0.79)

             

            D & B score = 12

              

            PA score

               • G4 = 0.65 (0.45-0.94)

             
               

            G1 =

              
               

            Inactive/occasional

            Regular walking

             
               

            G2 = Light

               • G1 = 1.00 (referent)

             
               

            G3 = Moderate

               • G2 = 1.15 (0.73-1.79)

             
               

            G4 = Moderately

               • G3 = 1.06 (0.75-1.50)

             
               

            vigorous/Vigorous

               • G4 = 0.97 (0.65-1.46)

             
               

            Regular walking (min/d)

               • G5 = 0.62 (0.37-1.05)

             
               

            G1 = 0

            Recreational activity

             
               

            G2 = <20

               • G1 = 1.00 (referent)

             
               

            G3 = 21-40

               • G2 = 0.95 (0.43-1.07)

             
               

            G4 = 41-60

               • G3 = 0.68 (0.43-1.07)

             
               

            G5 = ≥ 60

               • G4 = 0.34 (0.35-1.00)

             
               

            Recreational activity, 4 groups

            Sporting activity

             
               

            G1 = Inactive/fairly Inactive

               • G1 = 1.00 (referent)

             
               

            G2 = Average 4 hr/weekend

               • G2 = 0.50 (0.25-1.03)

             
               

            G3 = Fairly active >4 h/weekend

               • G3 = 0.88 (0.64-1.23)

             
               

            G4 = Very active

              
               

            Sporting activity, 3 Groups

              
               

            G1 = None

              
               

            G2 = Occasional

              
               

            G3 = >1 time/month

              

            Paffenbarger et al 1986 [63]

            To examine the PA and life-style characteristics of Harvard alumni for the relationship with all-cause mortality.

            • n = 16,936

            12-16 year follow-up (1962 to 1978)

               • 1,413 deaths

            The findings suggest a protective effect of exercise against all-cause mortality.

              

            • Sex: Men

             

            Age adjusted RR (95% CI):

             
              

            • Age: 35-74

               

            USA

             

            • Characteristics: Harvard alumni

            Records of freshman year physical examinations and records of intercollegiate sport

            Those who walked

             

            Prospective cohort

               

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.85

             
                

               • G3 = 0.79

             

            D & B score = 14

               

            Trend p = 0.0009

             
               

            PA assessment: Mailed questionnaires surveying post college

            Physical Activity Index (95% CI):

             
               

            PA

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.78

             
                

               • G3 = 0.73

             
                

               • G4 = 0.63

             
               

            Exercise reported: Walking (miles/wk) 3

               • G5 = 0.62

             
               

            groups

               • G6 = 0.52

             
               

            G1 = <3

               • G7 = 0.46

             
               

            G2 = 3-8

               • G8 = 0.62

             
               

            G3 = ≥ 9

              
                

            Trend p = <0.0001

             
               

            PA index (kcal/wk) 3 groups:

              
               

            G1 = <500

              
               

            G2 = 500-999

              
               

            G3 = 1000-1499

              
               

            G4 = 1500-1999

              
               

            G5 = 2000-2499

              
               

            G6 = 2500-2999

              
               

            G7 = 3000-3499

              
               

            G8 = >3500

              
               

            Cox proportional hazard models

              

            Schnohr et al 2007 [64]

            To determine the impact of walking duration and intensity on all-cause mortality.

            • n = 7,308 (3,204 male; 4,104 female)

            Baseline and an average of 12 year

               • 1,391 deaths

            The findings indicate that the relative intensity and not duration of walking is the most important in relation to all-cause mortality.

            Denmark

             

            • Sex: Male and female

            follow-up

            Multivariate adjusted HR (95% CI):

             
              

            • Age: 20-93 yr

            PA assessment: Questionnaire, 4 durations and 3 intensities

              

            Prospective cohort

             

            • Characteristics: Participants with no history of CHD, stroke or cancer and who had no difficulty in walking

             

            Men

             

            D & B score = 12

             

            • The Copenhagen City Heart Study

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.38 (0.25-0.58)

             
                

               • G3 = 0.38 (0.18-0.79)

             
               

            Duration (hours/day)

               • G4 = 0.69 (0.44-1.07)

             
               

            1 = <0.5

               • G5 = 0.37 (0.26-0.54)

             
               

            2 = 0.5-1

               • G6 = 0.33 (0.18-0.61)

             
               

            3 = 1-2

               • G7 = 0.78 (0.50-1.23)

             
               

            4 = >2

               • G8 = 0.41 (0.29-0.59)

             
                

               • G9 = 0.33 (0.20-0.54)

             
               

            Intensity

               • G10 = 0.43 (0.22-0.82)

             
               

            Slow intensity (SI)

               • G11 = 0.42 (0.29-0.60)

             
               

            Average intensity (AI)

               • G12 = 0.28 (0.16-0.48)

             
               

            Fast intensity (FI)

              
                

            Women

             
               

            12 groups

               • G1 = 1.00 (referent)

             
               

            G1 = 1 and SI

               • G2 = 0.82 (0.52-1.29)

             
               

            G2 = 1 and AI

               • G3 = 0.78 (0.27-2.21)

             
               

            G3 = 1 and FI

               • G4 = 1.22 (0.82-1.81)

             
               

            G4 = 2 and SI

               • G5 = 0.74 (0.52-1.05)

             
               

            G5 = 2 and AI

               • G6 = 0.56 (0.33-0.96)

             
               

            G6 = 2 and FI

               • G7 = 0.94 (0.60-1.47)

             
               

            G7 = 3 and SI

               • G8 = 0.87 (0.61-1.23)

             
               

            G8 = 3 and AI

               • G9 = 0.48 (0.28-0.83)

             
               

            G9 = 3 and FI

               • G10 = 0.88 (0.40-1.88)

             
               

            G10 = 4 and SI

               • G11 = 0.64 (0.44-0.95)

             
               

            G11 = 4 and AI

               • G12 = 0.38 (0.21-0.69)

             
               

            G12 = 4 and FI

              

            Kushi et al 1997 [65]

            To evaluate the association between PA and all-cause mortality in postmenopausal women.

            • n = 40,417

            7 year follow-up

            • 2,260 deaths

            The results demonstrate a graded inverse association between PA and all-cause mortality in postmenopausal women.

              

            • Sex: Women

               
              

            • Age: 55-69 yr

            PA assessment: Questionnaire for frequency of moderate and vigorous LTPA

            Multivariate adjusted Frequency of moderate PA per week RR (95% CI):

             

            USA

             

            • Characteristics: Postmenopausal Iowa women

               

            Prospective cohort

                 
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.71 (0.63-0.79)

             

            D & B score = 13

              

            Divided by frequency/week

            • G3 = 0.63 (0.56-0.71)

             
                

            • G4 = 0.59 (0.51-0.67)

             
               

            G1 = Rarely/never

            Trend p = <0.001

             
               

            G2 = 1 time/week to a few times/month

              
                

            Frequency of vigorous PA per week

             
               

            G3 = 2-4 times/week

              
               

            G4 = >4 times/week

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.83 (0.69-0.99)

             
                

            • G3 = 0.74 (0.59-0.93)

             
               

            Activity index

            • G4 = 0.62 (0.42-0.90)

             
               

            G1 = Low

            Trend p = 0.009

             
               

            G2 = Medium

              
               

            G3 = High

              
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.77 (0.69-0.86)

             
                

            • G3 = 0.68 (0.60-0.77)

             
                

            Trend p = <0.001

             

            Paffenbarger et al 1993 [67]

            To analyze changes in the lifestyles of Harvard College alumni and the association of these changes with mortality.

            • n = 10,269

            Baseline (1977) and 8 year follow-up (1985)

            • 476 deaths

            Beginning moderately vigorous sports activity was associated with lower rates of death from all causes among middle aged and older men.

              

            • Sex: Men

               
              

            • Age: 45-84 yr (in 1977)

             

            Beginning moderate sports activity was associated with 23% lower risk of death (95% CI 4%-42%, p = 0.015) than those not taking up moderate activity

             

            USA

             

            • Characteristics: Participants with no reported life- threatening disease

            PA Assessment: Questionnaire -- blocks walked daily, stairs climbed daily and type, frequency and duration of weekly sports and recreational activities

              

            Prospective cohort

                 

            D & B score = 13

                 
               

            Physical activity index (kcal/wk)

              
               

            Sports and recreational activities

              
               

            Light <4.5 METs

              
               

            Moderate >4.5 METs

              
               

            Weekly lists of deaths were obtained from the Harvard college alumni office

              
               

            Proportional hazard models with Poisson regression methods

              

            Katzmarzyk and Craig 2002 [154]

            To quantify the relationship between musculoskeletal fitness and all-cause mortality.

            • n = 8,116 (3,933 male; 4,183 female)

            Baseline (1981) and

            • 238 deaths

            Some components of musculoskeletal fitness are predictive of mortality.

               

            13 year follow-up

              
              

            • Sex: Men and women

             

            RR (95% CI) adjusted for age, smoking status, body mass and VO2max

             

            Canada

              

            Musculoskeletal fitness (sit ups, push ups, grip strength, sit and reach) measures divided into quartiles

              
              

            • Age: 20-69 yr

            Q1 = lowest

            Sit ups

             

            Prospective cohort

             

            • Characteristics: Participants who had musculoskeletal fitness measurements taken

            Q2

            Men

             
               

            Q3

            • Q1 = 2.72 (1.56-4.64)

             
               

            Q4 = highest

            • Q2 = 1.32 (0.73-2.41)

             

            D & B score = 11

               

            • Q3 = 1.61 (0.90-2.87)

             
                

            • Q4 = 1.00 (referent)

             
              

            • Canadian Fitness Survey

               
               

            Cox proportional hazard ratio model

            Women

             
                

            • Q1 = 2.26 (1.15-4.43)

             
                

            • Q2 = 2.24 (1.07-4.67)

             
                

            • Q3 = 1.27 (0.59-2.72)

             
                

            • Q4 = 1.00 (referent)

             
                

            Push-ups

             
                

            Men

             
                

            • Q1 = 1.25 (0.77-2.05)

             
                

            • Q2 = 1.17 (0.71-1.90)

             
                

            • Q3 = 0.94 (0.55-1.62)

             
                

            • Q4 = 1.00 (referent)

             
                

            Women

             
                

            • Q1 = 0.61 (0.32-1.17)

             
                

            • Q2 = 0.81 (0.45-1.47)

             
                

            • Q3 = 0.87 (0.48-1.58)

             
                

            • Q4 = 1.00 (referent)

             
                

            Grip strength (kg)

             
                

            Men

             
                

            • Q1 = 1.49 (0.86-2.59)

             
                

            • Q2 = 1.42 (0.82-2.45)

             
                

            • Q3 = 1.59 (0.95-2.68)

             
                

            • Q4 = 1.00 (referent)

             
                

            Women

             
                

            • Q1 = 1.08 (0.58-1.99)

             
                

            • Q2 = 0.62 (0.44-1.56)

             
                

            • Q3 = 1.25 (0.70-2.23)

             
                

            • Q4 = 1.00 (referent)

             
                

            Sit and reach (cm)

             
                

            Men

             
                

            • Q1 = 1.06 (0.64-1.74)

             
                

            • Q2 = 1.01 (0.61-1.66)

             
                

            • Q3 = 1.20 (0.74-1.95)

             
                

            • Q4 = 1.00 (referent)

             
                

            Women

             
                

            • Q1 = 1.18 (0.66-2.10)

             
                

            • Q2 = 1.07 (0.60-1.91)

             
                

            • Q3 = 0.77 (0.44-1.46)

             
                

            • Q4 = 1.00 (referent)

             

            Andersen et al 2000 [163]

            To evaluate the relationship between levels of OPA, LTPA, cycling to work and sports participation and all-cause mortality.

            • n = 30,640 (17,265 men; 13,375 women)

            14.5 year follow-up

            • 8,549 deaths

            LTPA was inversely associated with all-cause mortality in both men and women in all age groups.

               

            PA assessment: Questionnaire for LTPA, divided into:

            Incidence of all-cause mortality and PA

             

            Denmark

             

            • Sex: Men and women

               

            Prospective cohort

             

            • Age: 20-93 years (yr)

             

            Multivariate adjusted RR (95% CI)

             
               

            G1 = Low

              
              

            • Characteristics: Participants of the Copenhagen City Heart Study, Glostrup Population Study and Copenhagen Male Study

            G2 = Moderate

              

            D & B score = 13

              

            G3 = High

            Age 20-44 yr

             
                

            Men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.73 (0.56-0.96)

             
                

            • G3 = 0.74 (0.55-1.01)

             
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.75 (0.54-1.04)

             
                

            • G3 = 0.66 (0.42-1.05)

             
                

            Age 45-64 yr

             
                

            Men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.75 (0.67-0.84)

             
                

            • G3 = 0.75 (0.67-0.85)

             
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.73 (0.65-0.83)

             
                

            • G3 = 0.66 (0.56-0.77)

             
                

            Age >65 yr

             
                

            Men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.62 (0.53-0.73)

             
                

            • G3 = 0.60 (0.50-0.72)

             
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.52 (0.45-0.61)

             
                

            • G3 = 0.49 (0.39-0.61)

             
                

            All age groups

             
                

            Men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.72 (0.66-0.78)

             
                

            • G3 = 0.71 (0.65-0.78)

             
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.65 (0.60-0.71)

             
                

            • G3 = 0.59 (0.52-0.67)

             

            Barengo et al 2004 [164]

            To investigate whether moderate or high LTPA are associated with reduced CVD and all-cause mortality, independent of CVD risk factors and other forms of PA in men and women.

            • n = 31,677 (15,853 men; 16,824 women)

            20 year follow-up

            HRR (95% CI)

            Moderate and high levels of LTPA and OPA are associated with reduced premature all-cause mortality.

              

            • Sex: Men and women

            PA assessment: Questionnaire self administered to measure OPA, LTPA and commuting activity

            LTPA

             

            Finland

             

            • Age: 30-59 yr

             

               • 1.00 (referent) = low

             
              

            • Characteristics: Participants from eastern and south-western Finland

             

               • 0.91 (0.84-0.98) = mod, Men

             

            Prospective cohort

                 
                

               • 0.79 (0.70-0.90) = high, Men

             

            D & B score = 14

               

               • 0.89 (0.81-0.98) = mod, women

             
                

               • 0.98 (0.83-1.16) = high, women

             
                

            OPA

             
                

               • 1.00 (referent) = low

             
                

               • 0.75 (0.68-0.83) = mod, men

             
                

               • 0.77 (0.71-0.84) = active, men

             
                

               • 0.79 (0.70-0.89) = mod, women

             
                

               • 0.78 (0.70-0.87) = active, women

             

            Bath 2003 [165]

            To examine differences between older men and women on the self-rated health mortality relationship.

            • n = 1,042 (406 men; 636 women at baseline)

            Baseline, 4 and 12 years post

            Number of deaths: At 4 years 242 (106 men; 136 women)

            The self-rated health-mortality relationship can be explained by health and related factors among older men and women.

            UK

             

            • Sex: Men and women

             

            • At 12 years 665 (287 men; 378 women)

             

            Prospective cohort

             

            • Age: >65 yr

               
              

            • Characteristics: Community-dwelling Elderly

            General physical health

            14-item health index (Ebrahin et al 1987) scoring from 0-14 (no health problems -- multiple health problems)

            Multivariate adjusted HR (95% CI)

             

            D & B score = 11

                 
              

            • The Nottingham Longitudinal Study of Activity and Ageing

               
                

            Men after 4 years

             
                

            • High = 1.00 (referent)

             
                

            • Med = 1.19 (0.61-2.33)

             
               

            PA assessment: Self-rated health surveys, divided into 3 levels of PA:

            • Low = 1.51 (0.75-3.03)

             
               

            High

            Women after 4 years

             
               

            Medium

            • High = 1.00 (referent)

             
               

            Low

            • Med = 1.03 (0.58-1.82)

             
                

            • Low = 1.51 (0.86-2.67)

             
                

            Men after 12 years

             
               

            Cox proportional hazards regression Models

            • High = 1.00 (referent)

             
                

            • Med = 1.28 (0.94-1.74)

             
                

            • Low = 1.13 (0.82-1.55)

             
                

            Women after 12 years

             
                

            • High = 1.00 (referent)

             
                

            • Med = 1.20 (0.90-1.61)

             
                

            • Low = 1.23 (0.93-1.62)

             

            Bijnen et al 1998 [166]

            To describe the association between PA and mortality (CVD, stroke, all-cause) in elderly men.

            • n = 802

            10 year follow-up

            • 373 deaths

            PA may protect against all- cause mortality in elderly men

              

            • Sex: Men

               
              

            • Age: 64-84 yr

            PA assessment: Questionnaire, divided into groups:

            Multivariate adjusted RR (95% CI)

             

            Netherlands

             

            • Characteristics: Retired Dutch men

               
                

            • G1 = 1.00 (referent)

             

            Prospective cohort

              

            G1 = Lowest

            • G2 = 0.80 (0.63-1.02)

             
               

            G2 = Middle

            • G3 = 0.77 (0.59-1.00)

             
               

            G3 = Highest

            p = 0.04

             

            D & B score = 12

                 

            Blair et al 1993 [167]

            To evaluate the relationship of sedentary living habits to all-cause mortality in women.

            • n = 3,120

            Baseline and 8 year follow-up

            • 43 deaths

            There is a graded inverse relationship between PF and all-cause mortality in women.

              

            • Sex: Women

               
              

            • Age: Not available

             

            Age adjusted death rates (per 10,000 person years) by fitness

             

            USA

             

            • Characteristics: Participants were given a preventative medicine examination

            PF assessment: PF measured via maximal treadmill exercise test;

              

            Prospective

               

               • Low Fitness = 40

            The lack of relationship between PA and death rate was believed to be due to an inadequate assessment of PA.

                

               • Mod Fitness = 16

             

            D & B score = 14

               

               • High Fitness = 7

             
               

            PA assessment: Questionnaire

              
                

            No difference between levels of PA

             

            Blair et al 1996 [168]

            To review the association of PF to all-cause and CVD mortality.

            • n = 32,421 (25,341 men; 7,080 women)

            Baseline and average 8 year follow-up (range 0.1-19.1 years)

            • 601 deaths in men

            The study observed a steep inverse gradient of death rates across low, moderate and high PF levels. The association was strong and remained after adjustment for potential confounding factors.

                

            • 89 deaths in women

             
              

            • Sex: Men and women

               

            USA

             

            • Age: 20-80 yr (mean 43 yr)

             

            RR (95% CI) in low PF vs.

             
               

            PF assessment: Treadmill test; duration was used to assign participants to sex specific groups:

            high PF

             

            Prospective cohort

             

            • Characteristics: Participants were excluded if they did not reach 85% of their age predicted maximal heart rate on the maximal exercise treadmill test

             

            Men

             
                

            • 1.52 (1.28-1.82)

             
                

            Women

             

            D & B score = 14

               

            • 2.10 (1.36-3.26)

             
               

            Low (least fit 20%)

            Adjusted deaths per 10,000 person years according to PF

             
               

            Moderate (next 40%)

              
               

            High (most fit 40%)

            Men

             
              

            • Aerobics Center Longitudinal Study

            Proportional hazard modeling

            • Low = 49

             
                

            • Med = 27

             
                

            • High = 23

             
                

            Women

             
                

            • Low = 29

             
                

            • Med = 13

             
                

            • High = 14

             

            Boyle et al 2007 [169]

            To examine the association between PA and the risk of incident disability, including impairment in activities of daily living and instrumental activities of daily living in community based older persons free from dementia.

            • n = 1,020

            2.6 year follow-up

            • 156 deaths

            The risk of death decreased 11% with each hour of PA/wk.

              

            • Sex: Men and women

               
              

            • Age: 54-100 yr

            PA assessment: Questionnaire, hr/wk of PA Incidence of all-cause mortality

            HR for all-cause mortality

             

            USA

             

            • Characteristics: Participants from 40 retirement communities across Chicago

             

            The risk of death was 11% lower for each hr/wk of PA

             

            Prospective cohort

                 

            D & B score = 13

             

            • Rush Memory and Aging Project

               

            Bucksch et al 2005 [170]

            To examine the effect of moderately intense PA on all-cause mortality.

            • n = 7,187 (3,742 men; 3,445 women)

            Baseline (1984-1986) and 12-14 yr follow-up (1998)

            • 943 deaths

            Participants who achieved recommended amounts of MPA or VPA were at a significantly lower risk of death than their sedentary counterparts.

              

            • Sex: Men and women

             

            RR (95% CI) for achieving recommended PA vs. not achieving recommendation

             

            Germany

             

            • Age: 30-69 yr

               

            Prospective cohort

             

            • Characteristics: Participants were healthy and physically active during leisure time

            PA assessment: Questionnaire (Minnesota Leisure Time Physical Activity questionnaire) divided into groups based on: Achieving recommended amount of MPA (30 min, 5 d/wk (≥2.5 h/wk))

              
                

            Women

             
                

            • MPA = 0.65 (0.51-0.82)

             

            D & B score = 13

               

            • VPA = 0.78 (0.57-1.08)

             
                

            • MPA or VPA = 0.60 (0.47-0.75)

             
                

            Men

             
                

            • MPA = 0.90 (0.77-1.01)

             
                

            • VPA = 0.74 (0.61-0.90)

             
                

            • MPA or VPA = 0.80 (0.68-0.94)

             
               

            Achieving recommended amount of VPA (20 min, 3 d/wk (≥ 1 h/wk))

              
                

            RR (95% CI) for volume of lifestyle activities (kcal/kg/wk)

             
               

            Volume of lifestyle activities (kcal/kg/wk)

            Women

             
               

            G1 = 0

            • G1 = 1.00 (referent)

             
               

            G2 = <14

            • G2 = 0.79 (0.57-1.08)

             
               

            G3 = 14-33.5

            • G3 = 0.68 (0.50-0.94)

             
               

            G4 = ≥ 33.5

            • G4 = 0.57 (0.41-0.79)

             
                

            p < 0.001

             
                

            Men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.98 (0.76-1.17)

             
                

            • G3 = 0.80 (0.63-1.00)

             
                

            • G4 = 0.91 (0.74-1.13)

             
                

            p = 0.20

             
                

            Adjusted for age, other recommendation, social class, smoking, BMI, cardio risk factor index, alcohol intake, chronic disease index and dietary factors

             

            Bucksch and Helmert 2004 [171]

            To examine LTPA and premature death in the general population of former West Germany.

            • n = 7,187 (3,742 men; 3,445 women)

            Baseline (1984-1986) and 12-14 year follow-up (1998)

            • 943 deaths

            LTPA is inversely associated with all-cause mortality in men and women.

              

            • Sex: Men and women

             

            RR (95% CI)

             
              

            • Age: 30-69 yr

             

            Men, LTPA

             

            Germany

             

            • Characteristics: Participants were selected on the basis of the German Cardiovascular Prevention Study

            PA assessment: Questionnaire (Minnesota Leisure Time Physical Activity questionnaire) divided into groups based on: LTSA (h/wk)

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.85 (0.78-0.93)

             

            Prospective cohort

               

            • G3 = 0.64 (0.50-0.82)

             
                

            • G4 = 0.70 (0.54-0.91)

             
                

            p < 0.001

             

            D & B score = 14

             

            • The National Health Survey of the German Federal Institute of Population Research (1984-1998)

             

            Men, LTPA index

             
               

            G1 = 0

            • G1 = 1.00 (referent)

             
               

            G2 = <1

            • G2 = 0.92 (0.70-1.23)

             
               

            G3 = 1-2

            • G3 = 0.89 (0.69-1.17)

             
               

            G4 = >2

            • G4 = 0.61 (0.44-0.84)

             
                

            p <0.01

             
               

            The LTSA-index (kcal/kg/wk)

              
               

            G1 = 0

            Women, LTPA

             
               

            G2 = 1-10

            • G1 = 1.00 (referent)

             
               

            G3 = 10-25

            • G2 = 0.93 (0.82-1.04)

             
               

            G4 = >25

            • G3 = 0.69 (0.48-0.98)

             
                

            • G4 = 0.57 (0.35-0.94)

             
               

            Mortality -- Records from the mandatory population registries

            p < 0.01

             
                

            Women, LTPA index

             
                

            • G1 = 1.00 (referent)

             
               

            Cox proportional hazard regression model

            • G2 = 0.68 (0.45-1.01)

             
                

            • G3 = 0.79 (0.51-1.21)

             
                

            • G4 = 0.46 (0.25-0.85)

             
                

            p < 0.01

             
                

            Adjusted for age, social class, smoking, BMI, cardio risk factor index, alcohol intake, chronic disease index and dietary factors

             

            Carlsson et al 2006 [172]

            To investigate the association between PA and mortality in post-menopausal women.

            • n = 27,734

            Baseline (1997) and 2-7 year follow-up (1999-2004)

            • 1,232 deaths

            The study indicates that even fairly small amounts of activity will reduce mortality in older women.

              

            • Sex: Women

               
              

            • Age: 51-83 yr

             

            RR (95% CI) adjusted for lifestyle and medical problems

             

            Sweden

             

            • Characteristics: Women who participated in a population based Screening programme in 1987

               

            Prospective cohort

              

            PA assessment: Questionnaires for: METs/day, different PA (walking/biking), LTPA, OPA, household PA, TV watching and reading

              
                

            PA (METs/day)

             
                

            • >50 = 1.00 (referent)

             

            D & B score = 12

               

            • 45-50 = 1.05 (0.77-1.42)

             
              

            • The Swedish Mammography Cohort

             

            • 40-45 s = 1.09 (0.81-1.46)

             
                

            • 45-40 = 1.26 (0.94-1.70)

             
                

            • <35 = 2.56 (1.85-3.53)

             
               

            Mortality -- Records from the National Population Register

              
                

            Different PA

             
                

            Walking/biking (min/d)

             
                

            • > 90 = 1.00 (referent)

             
                

            • 60-90 = 1.01 (0.76-1.34)

             
                

            • 40-60 = 0.92 (0.70-1.20)

             
                

            • 20-40 = 0.96 (0.75-1.23)

             
                

            • <20 = 1.16 (0.90-1.50)

             
                

            • Almost never = 1.94 (1.51-2.50)

             
                

            LTPA (hr/wk)

             
                

            • >5 = 1.00 (referent)

             
                

            • 4-5 = 0.95 (0.74-1.22)

             
                

            • 2-3 = 1.02 (0.83-1.26)

             
                

            • 1 = 1.09 (0.88-1.36)

             
                

            • <1 = 1.91 (1.56-2.35)

             
                

            OPA

             
                

            • Heavy manual labour = 1.00 (referent)

             
                

            • Walking/lifting/ a lot carrying = 0.96 (0.55-1.70)

             
                

            • Walking/lifting/ not a lot carrying = 1.00 (0.60-1.68)

             
                

            • Mostly standing = 0.91 (0.52-1.61)

             
                

            • Seated 50% of time = 0.97 (0.58-1.62)

             
                

            • Mostly sedentary = 1.93 (1.15-3.25)

             
                

            Household work (hr/d)

             
                

            • >8 h/d = 1.00 (referent)

             
                

            • 7-8 = 0.68 (0.49-0.93)

             
                

            • 5-6 = 0.66 (0.51-0.87)

             
                

            • 3-4 = 0.83 (0.64-1.06)

             
                

            • 1-2 = 0.89 (0.69-1.15)

             
                

            • <1 = 1.73 (1.30-2.32)

             
                

            Adjusted for age

             

            Crespo et al 2002 [173]

            To study the relationship between PA and obesity with all- cause mortality in Puerto Rican men.

            • n = 9,136 (1962-1965)

            Baseline and 12 year follow-up

            • 1,445 deaths

            Some PA is better than none in protecting against all-cause mortality. The benefits are independent of body weight.

            Puerto Rico

             

            • Sex: Men

            PA assessment: Questionnaire, divided into 4 groups based on METs

            Multivariate OR (95% CI) adjusted for age

             
               

            G1 = low

              
               

            G2

              
               

            G3

              
               

            G4 = high

              

            Prospective cohort

             

            • Age: 35-79 yr

            Multivariate logistic function model

            • C1 = 1.00 (referent)

             

            D & B score = 12

             

            • Characteristics: Participants with no known coronary heart disease

             

            • C2 = 0.67 (0.57-0.78)

             
              

            • The Puerto Rico Heart Health Program

             

            • C3 = 0.63 (0.54-0.74)

             
                

            • C4 = 0.54 (0.46-0.64)

             
                

            p < 0.0001

             
                

            Multivariate adjusted OR (95% CI)

             
                

            • C1 = 1.00 (referent)

             
                

            • C2 = 0.68 (0.58-0.79)

             
                

            • C3 = 0.63 (0.54-0.75)

             
                

            • C4 = 0.55 (0.46-0.65)

             
                

            p < 0.0001

             

            Davey Smith et al

            2000 [174]

            To examine the relationship of PA and various causes of death.

            • n = 6,702 (at baseline)

            Baseline (1969-1970) and 25 year follow-up

            • 926 deaths

            In the study, an inverse association of both LTPA and walking pace with mortality from all-causes was seen.

            UK

             

            • Sex: Men

            PA assessment: Questionnaire with 3 groups for walking pace (Slower, same, faster) and 3 groups for LTPA (inactive, moderately active, active)

            Age adjusted RR (95% CI) for walking pace

             

            Prospective cohort

             

            • Age: 40-64 yr

             

            • Slower = 2.47 (2.2-2.8)

             

            D & B score = 13

             

            • Characteristics: Participants from rural northern Japan

             

            • Same = 1.35 (1.2-1.5)

             
              

            • Whitehall study

             

            • Faster = 1.00 (referent)

            p < 0.001

             
                

            Fully adjusted RR (95% CI) for walking pace

             
                

            • Slower = 1.87 (1.6-2.1)

             
                

            • Same = 1.21 (1.1-1.3)

             
                

            • Faster = 1.00 (referent)

            p < 0.001

             
                

            Age adjusted RR (95% CI) for LTPA

             
                

            • Inactive = 1.44 (1.3-1.6)

             
                

            • Mod = 1.13 (1.0-1.2)

             
                

            • Active = 1.00 (referent)

            p < 0.001

             
                

            Fully adjusted RR (95% CI) for LTPA

             
                

            • Inactive = 1.20 (1.1-1.3)

             
                

            • Mod = 1.07 (1.0-1.2)

             
                

            • Active = 1.00 (referent)

            p < 0.001

             

            Eaton et al 1995 [175]

            To determine whether self-reported PA predicts a decreased rate of CHD and all- cause mortality in middle aged men.

            • n = 8,463

            21 year follow-up

            • 2,593 deaths

            Baseline levels of self- reported LTPA predicted a decreased rate of CHD and all-cause mortality.

            Europe, Israel, mid eastern Asia, Northern Africa

             

            • Sex: Men

            PA assessment: Questionnaire for LTPA

            Age adjusted RR (95% CI) LTPA

             

            Prospective cohort

             

            • Age: ≥40 yr

            G1 = Sedentary

            • G1 = 1.00 (referent)

             

            D & B score = 12

             

            • Characteristics: Government employees without known CVD

            G2 = Light

            • G2 = 0.84 (0.74-0.94)

             
               

            G3 = Light daily

            • G3 = 0.81 (0.73-0.90)

             
               

            G4 = Heavy

            • G4 = 0.84 (0.72-0.98)

             
                

            OPA

             
               

            Questionnaire for OPA

            • G1 = 1.00 (referent)

             
               

            G1 = Sitting

            • G2 = 0.99 (0.88-1.12)

             
               

            G2 = Standing

            • G3 = 1.09 (0.99-1.20)

             
               

            G3 = Walking

            • G4 = 1.16 (1.03-1.30)

             
               

            G4 = Physical labour

              

            Fang et al 2005 [176]

            To assess the association of exercise and CVD outcome among persons with different blood pressure status.

            • n = 9,791 (3,819 men; 5,972 women)

            17 year follow-up

            Incidence of all-cause mortality and PA

            A significant effect of exercise on mortality in normotensive subjects was not found.

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire with 3 groups

            Multivariate adjusted HR (95% CI)

             

            Prospective cohort

             

            • Age:25-74 yr

            G1 = Least exercise

            • G1 = 1.00 (referent)

             

            D & B score = 12

             

            • Characteristics: Non- institutionalized participants

            G2 = Moderate exercise

            • G2 = 0.75 (0.53-1.05)

             
               

            G3 = Most exercise

            • G3 = 0.71 (0.45-1.12)

             

            Fried et al 1998 [177]

            To determine the disease, functional and personal characteristics that jointly predict mortality.

            • n = 5,886

            5 year follow-up

            • 646 deaths

            PA was a predictor of 5-year mortality.

            USA

             

            • Sex: Men and women

            PA assessment: Self reported exercise (5 groups)

            Incidence of all-cause mortality and PA

             

            Prospective cohort

             

            • Age: ≥65 yr

            MPA or VPA (kJ/wk)

            Multivariate adjusted RR (95% CI)

             

            D & B score = 11

             

            • Characteristics: Community dwelling elders

            G1 = ≤282

            • G1 = 1.00 (referent)

             
               

            G2 = 283-1789

            • G2 = 0.78 (0.60-1.00)

             
               

            G3 = 1790-4100

            • G3 = 0.81 (0.63-1.05)

             
               

            G4 = 4101-7908

            • G4 = 0.72 (0.55-0.93)

             
               

            G5 = >7908

            • G5 = 0.56 (0.43-0.74)

            p < 0.005

             

            Fujita et al 2004 [178]

            To examine the relationship between walking duration and all-cause mortality in a Japanese cohort.

            • n = 41,163 (20,004 men; 21,159 women)

            Baseline (1990) and 11 year follow-up (2001)

            • 1,879 deaths

            Time spent walking was associated with a reduced risk for all-cause mortality.

            Japan

             

            • Sex: Men and women

            PA assessment: Questionnaire Walking, 3 levels:

            Age and sex adjusted RR (95% CI) for time spent walking (hr/d)

             
               

            G1 = ≤30 min

              
               

            G2 = 30 min to 1 hr

              
               

            G3 = ≥1 hr

              

            Prospective cohort

             

            • Age: 40-64 yr

            Cox proportional hazard model

            Whole group

             

            D & B score = 13

             

            • Characteristics: Healthy, sedentary

             

            • G1 = 1.22 (1.09-1.35)

             
                

            • G2 = 1.09 (0.95-1.22)

             
                

            • G3 = 1.00 (referent)

            p < 0.001

             
                

            Men only

             
                

            • G1 = 1.14 (1.00-1.30)

             
                

            • G2 = 1.03 (0.90-1.19)

             
                

            • G3 = 1.00 (referent p = 0.061

             
                

            Women only

             
                

            • G1 = 1.40 (1.16-1.68)

             
                

            • G2 = 1.23 (1.01-1.49)

             
                

            • G3 = 1.00 (referent)

            p < 0.001

             
                

            RR (95% CI) for time spent walking (hr/d) (adjusted for age, education, marital status, past history of diseases, smoking, drinking, BMI and dietary variables)

             
                

            Whole group

             
                

            • G1 = 1.17 (1.04-1.31)

             
                

            • G2 = 1.06 (0.93-1.20)

             
                

            • G3 = 1.00 (referent)

            p = 0.011

             
                

            Men

             
                

            • G1 = 1.08 (0.94-1.25)

             
                

            • G2 = 0.98 (0.84-1.14)

             
                

            • G3 = 1.00 (referent)

            p = 0.318

             
                

            Women

             
                

            • G1 = 1.38 (1.12-1.70)

             
                

            • G2 = 1.24 (1.00-1.54)

             
                

            • G3 = 1.00 (referent)

            p < 0.001

             

            Glass et al 1999 [179]

            To examine any association between social activity, productive activity and PA and mortality in older people.

            • n = 2,761 (1,169 men; 1,143 women)

            13 year follow-up

            Incidence of all-cause mortality by fitness activity quartile

            More active elderly people were less likely to die than those who were less active.

            USA

             

            • Sex: Men and women

            PA assessment: Interview, Amount of activity

            13 yr mortality by amount of activity

             

            Prospective cohort

             

            • Age: ≥ 65 yr

            G1 = Low

            • G1 = 74.0

             

            D & B score = 12

             

            • Characteristics: Healthy elders

            G2 = Low-medium

            • G2 = 69.8

             
               

            G3 = Medium-high

            • G3 = 62.4

             
               

            G4 = High

            • G4 = 55.2

             

            Gulati et al 2003 [180]

            To determine whether exercise capacity is a predictor for all-cause mortality in asymptomatic women.

            • n = 5,721

            Baseline (1992) and 8 year follow-up (2000)

            • 180 deaths

            This study confirmed that exercise capacity is an independent predictor of death in asymptomatic women, greater than what has been previously established among men.

            USA

             

            • Sex: Women

            PF Assessment: Treadmill stress test Exercise capacity (METs)

            G1 = <5

            G2 = 5-8

            G3 = >8

            For every 1 MET increase there was a reduced death risk of 17% (p < 0.001)

             

            Prospective cohort

             

            • Age: Mean 52 ± 11 yr

             

            Age-adjusted RR

             

            D & B score = 11

             

            • Characteristics: Asymptomatic women

             

            • G1 = 2.0 (1.3-3.2)

             
              

            • St James Women Take Heart Project

             

            • G2 = 1.6 (1.1-2.4)

             
                

            • G3 = 1.00 (referent)

             
                

            Adjusted for Framingham

            Risk Score

             
                

            • G1 = 3.1 (2.1-4.8)

             
                

            • G2 = 1.9 (1.3-2.9)

             
                

            • G3 = 1.00 (referent)

             

            Haapanen et al 1996 [181]

            To examine the association between LTPA and all-cause mortality.

            • n = 1,072

            Baseline and a 10 yr

            10 month follow-up

            • 168 deaths

            Low PA is a risk factor for all-cause mortality.

            Finland

             

            • Sex: Men

            PA assessment: Self-reported LTPA, divided into 4 groups by EE (kJ/wk)

            G1 = 0-3349

            G2 = 3350-6279

            G3 = 6280-8791

            G4 = >8791

            RR (95% CI) according to EE group

             

            Prospective cohort

             

            • Age: 35-63 yr

            Mortality--National

            Death Index search

            • G1 = 2.74 (1.46-5.14)

             

            D & B score = 14

             

            • Characteristics: Healthy, sedentary

            Cox proportional HR

            • G2 = 1.10 (0.55-2.21)

             
                

            • G3 = 1.74 (0.87-3.50)

             
                

            • G4 = 1.00 (referent)

             

            Hakim et al 1998 [182]

            To examine the association between walking and mortality in retired men.

            • n = 707

            Baseline and 12 yr follow-up

            • 208 deaths

            The findings in older physically capable men indicate that regular walking is associated with a lower overall mortality rate.

            USA

             

            • Sex: Men

             

            RR (95% CI) according to distance walked

             

            Prospective cohort

             

            • Age: 61-81 yr

             

            Adjusted for age

             

            D & B score = 12

             

            • Characteristics: Retired non-smoking men who were physically capable of participating in low intensity activities on a daily basis

            PA assessment: Questionnaire Distance walked (miles/day)

            • G1 vs. G3 = 1.9 (1.3-2.9)

             
               

            G1 = 0.0-0.9

            • G1 vs. G3 = 1.6 (1.2-2.2)

             
               

            G2 = 1.0-2.0

            • G2 vs. G3 = 1.2 (0.8-1.7)

             
               

            G3 = 2.1-8.0

            Trend p = 0.002

             
              

            • Honolulu Heart Program

               
                

            Adjusted for risk factors

             
                

            • G1 vs. G3 = 1.8 (1.2-2.7)

             
                

            • G1 vs. G2 = 1.5 (1.1-2.1)

             
                

            • G2 vs. G3 = 1.1 (0.8-1.7)

             
                

            Trend p = 0.01

             

            Hillsdon et al 2004 [183]

            To examine whether VPA is associated with all-cause mortality.

            • n = 10,522 (4,929 men; 5,593 women)

            >10 year follow-up

            • 825 deaths

            Questionnaire respondents who reported engaging in VPA less than twice a week experienced a 37% reduced risk of all-cause mortality compared with respondents who reported a lower frequency of VPA.

              

            • Sex: Men and women

            PA assessment: Questionnaire for frequency of VPA

            Age and sex adjusted RR (95% CI)

             

            UK

             

            • Age: 35-64 yr

            G1 = Never, <1 time/month

              
              

            • Characteristics: Healthy, sedentary

            G2 = <2 times/wk

            • G1 = 1.00 (referent)

             

            Prospective Cohort

             

            • OXCHECK study

            G3 = >2 times/wk

            • G2 = 0.57 (0.42-0.79)

             
                

            • G3 = 0.72 (0.54-0.95)

             

            D & B score = 11

               

            Fully adjusted RR (95% CI)

             
                

            • G1 = 1.00 (referent)

             
               

            Mortality -- Recorded from the Office of National Statistics

            • G2 = 0.63 (0.45-0.89)

             
                

            • G3 = 0.81 (0.60-1.09)

             
               

            Cox proportional HR

              

            Hu et al 2005 [184]

            To examine the association of PA and BMI and their combined effect with the risk of total, CVD and cancer mortality.

            • n = 47,212 (22,528 men; 24,684 women)

            17.7 year follow-up

            • 7,394 deaths

            Regular PA is an important indicator for decreased risk of all-cause mortality. PA has a strong independent effect on mortality.

              

            • Sex: Men and women

               

            Finland

             

            • Age:25-64 yr

            PA assessment: Questionnaire for PA level, divided into 3 groups

            Adjusted HR (95% CI)

             
              

            • Characteristics: Participants from eastern Finland

             

            Men

             

            Prospective cohort

               

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.74 (0.68-0.81)

             
               

            G1 = Low

            • G3 = 0.63 (0.58-0.70)

             

            D & B score = 12

              

            G2 = Moderate

            Trend p = <0.001

             
               

            G3 = High

              
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.64 (0.58-0.70)

             
                

            • G3 = 0.58 (0.52-0.64)

             
                

            Trend p = <0.001

             

            Hu et al 2004 [185]

            To examine the association of BMI and PA with death.

            • n = 116,564

            Baseline (1976) and

            • 10,282 deaths

            Reduced PA is a strong and independent predictor of death.

              

            • Sex: Women

            24 year follow-up

              
              

            • Age: 30-55 yr

             

            Multivariate RR (95% CI) by PA (hr/wk)

             

            USA

             

            • Characteristics: Females free of known CVD and cancer

            PA assessment: Questionnaire for PA level, divided into 3 groups (hr/week)

            • G1 = 1.00 (referent)

             
               

            G1 = ≥ 3.5

            • G2 = 1.18 (1.10-1.26)

             

            Prospective cohort

              

            G2 = 1.0-3.4

            • G3 = 1.52 (1.41-1.63)

             

            D & B score = 11

              

            G3 = <1.0

            Multivariate RR (95% CI) by PA adjusted for BMI

             
                

            • G1 = 1.00 (referent)

             
               

            BMI (kg/m2)

            • G2 = 1.14 (1.06-1.22)

             
               

            G1 = <25

            • G3 = 1.44 (1.34-1.55)

             
               

            G2 = 25-29

              
               

            G3 = 30

              
               

            Cox proportional HR

              

            Kampert et al 1996 [186]

            To examine PF and PA in relation to all-cause and cancer mortality.

            • n = 32,421 (25,341 men; 7,080 women)

            Baseline (1970) and ~8 year follow-up (1989)

            • 690 deaths

            The data support the hypothesis that an active and fit way of life delays death.

              

            • Sex: Men and women

             

            Adjusted RR (95% CI) by quintiles of activity

             

            USA

             

            • Age: 20-88 yr (mean ~43)

               

            Prospective cohort

             

            • Characteristics: Predominantly white and from the middle and upper socioeconomic strata

            PA assessment: Questionnaire, divided into quintiles of activity (min/wk)

            Men

             
                

            • Sedentary = 1.00 (referent)

             
                

            • C1-2 = 0.71 (0.58-0.97)

             

            D & B score = 13

               

            • C3 = 0.83 (0.59-1.16)

             
               

            Male activity categories

            • C4 = 0.57 (0.30-1.08)

             
                

            • C5 = 0.92 (0.29-2.88)

             
               

            Sedentary = 855

            Trend p = 0.011

             
               

            C1-2 = 1,072

              
               

            C3 = 1,292

            Women

             
               

            C4 = 1,453

            • Sedentary = 1.00 (referent)

             
               

            C5 = 1,601

            • C1-2 = 0.68 (0.39-1.17)

             
                

            • C3 = 0.39 (0.09-1.65)

             
               

            Females activity categories

            • C4-5 = 1.14 (0.27-4.80)

             
               

            Sedentary = 605

            Trend p = 0.217

             
               

            C1-2 = 792

              
               

            C3 = 979

              
               

            C4-5 = 1,158

              
               

            Cox proportional HR

              

            Kaplan et al 1996 [187]

            To assess LTPA and its association with all cause mortality.

            • n = 6,131 (3298 men; 2833 women)

            28 year follow-up

            • 1,226 deaths

            The data provide further support for the importance of PA and indicate that the protective effect of PA is a robust one.

              

            • Sex: Men and women

            PA assessment: Three questions about PA, with scores 0 (never), 2 (sometimes) or 4 (often).

            Incidence of all-cause mortality and PA

             

            USA

             

            • Age: 16-94 yr

               
              

            • Characteristics: Northern Californian adults

               

            Prospective cohort

               

            Death rates/1000 person years

             
                

            Men

             

            D & B score = 13

               

            • T1 = 24.68

             
               

            Tertiles of PA score

            • T2 = 11.37

             
               

            T1 = 0-2

            • T3 = 7.59

             
               

            T2 = 4-6

            Women

             
               

            T3 = 8-12

            • T1 = 18.03

             
                

            • T2 = 7.66

             
                

            • T3 = 3.88

             

            Khaw et al 2006 [188]

            To examine the relationship between PA patterns over 1 year and total mortality.

            • n = 22,191 (9,984 men; 12,207 women)

            8 year follow-up

            • 1,553 deaths

            Even very moderate levels of usual PA are associated with reductions in mortality.

              

            • Sex: Men and women

            PA assessment: Questionnaire, divided into 4 groups of PA

            Incidence of all-cause mortality and PA

             

            UK

             

            • Age: 45-79 yr

             

            Adjusted RR (95% CI)

             
              

            • Characteristics: Community living participants

             

            All

             

            Prospective cohort

              

            G1 = Inactive

            • G1 = 1.00 (referent)

             
               

            G2 = Moderately inactive

            • G2 = 0.83 (0.73-0.95)

             

            D & B score = 13

               

            • G3 = 0.68 (0.58-0.80)

             
               

            G3 = Moderately active

            • G4 = 0.68 (0.57-0.81)

             
               

            G4 = Active

            Age <65

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 1.01 (0.78-1.31)

             
                

            • G3 = 0.81 (0.62-1.07)

             
                

            • G4 = 0.82 (0.62-1.09)

             
                

            Age >65

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.77 (0.66-0.91)

             
                

            • G3 = 0.65 (0.53-0.79)

             
                

            • G4 = 0.64 (0.50-0.80)

             

            Kohl et al 1996 [189]

            To determine the association of maximal exercise hemodynamic responses with risk of all-cause mortality.

            • n = 26,621 (20,387 men; 6,234 women)

            Average 8.1 year follow-up

            • 348 deaths in men and 66 in women

            The results suggest an exaggerated SBP or an attenuated heart rate response to maximal exercise may indicate an elevated risk for mortality.

              

            • Sex: Men and women

               

            USA

             

            • Age: Male mean 42.2 yr; female mean 41.9 Yr

             

            Adjusted RH (95% CI) by maximal exercise test HR

             

            Prospective cohort

               

            Men

             
              

            • Characteristics: Apparently healthy patients of a preventive medicine centre

            PF assessment: Maximal exercise test HR (bpm), divided into 4 Groups:

            • Q1 = 1.00 (referent)

             
               

            G1 = <171

            • Q2 = 0.61 (0.44-0.85)

             

            D & B score = 12

              

            G2 = 171-178

            • Q3 = 0.69 (0.51-0.93)

             
               

            G3 = 179-188

            • Q4 = 0.60 (0.41-0.87)

             
               

            G4 = >188

            Trend p<0.05

             
                

            Women

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 1.23 (0.65-2.32)

             
                

            • Q3 = 0.69 (0.30-1.63)

             
                

            • Q4 = 0.71 (0.22-2.24)

             
                

            Trend p>0.05

             

            Kujala et al 1998 [190]

            To investigate LTPA and mortality in a cohort of twins.

            • n = 15,902 (7,925 men; 7,977 women)

            Baseline 1975 and death outcome from 1977-1994

            • 1,253 deaths

            LTPA is associated with reduced mortality, even after genetic and other familial factors are taken into account.

              

            • Sex: Men and women

             

            HR (95% CI)

             

            Finland

             

            • Age: 25-64 yr

               
              

            • Characteristics: Healthy, Finnish same sex twins

            PA assessment: Questionnaire, quintiles of fitness in MET hours/day

            Adjusted for age and sex

             

            Prospective cohort

               

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.71 (0.62-0.81)

             
              

            • The Finnish Twin Cohort

             

            • CE = 0.57 (0.45-0.74)

             

            D & B score = 13

              

            Q1 = <58

            Trend p = 0.001

             
               

            Q2 = 59-1.29

              
               

            Q3 = 1.30-2.49

            Adjusted for age, sex, smoking

             
               

            Q4 = 2.50-4.49

              
               

            Q5 = >4.50

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.76 (0.67-0.87)

             
               

            Categorized into:

            • CE = 0.68 (0.53-0.88)

             
               

            -Sedentary

              
               

            -Occasional exerciser (OE)

            Trend p = 0.001

             
               

            -Conditioning exerciser (CE)

            Adjusted for age, sex, smoking, occupational group, alcohol

             
                

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.80 (0.69-0.91)

             
                

            • CE = 0.76 (0.59-0.98)

             
                

            Trend p = 0.002

             
                

            HR (95% CI) among 434 same sex twin pairs compared with sedentary category in 1975

             
                

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.66 (0.46-0.94)

             
                

            • CE = 0.44 (0.23-0.83)

             
                

            Trend p = 0.005

             
                

            Adjusted for smoking

             
                

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.70 (0.48-1.01)

             
                

            • CE = 0.56 (0.29-1.09)

             
                

            Trend p = 0.04

             
                

            Adjusted for smoking, occupational group, alcohol

             
                

            • Sedentary = 1.00 (referent)

             
                

            • OE = 0.73 (0.50-1.07)

             
                

            • CE = 0.56 (0.29-1.11)

             
                

            Trend p = 0.06

             
                

            OR (95% CI) in quintiles among 434 same sex twin pairs compared with sedentary category in 1975

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 0.85

             
                

            • Q3 = 0.72

             
                

            • Q4 = 0.68

             
                

            • Q5 = 0.60

             

            LaCroix et al 1996 [191]

            To determine whether walking is associated with a reduced risk of CVD hospitalization and death in older adults.

            • n = 1,645 (615 men; 1030 women)

            4.2 year follow-up

            RR (95% CI) by category of walking

            Walking more than 4 hr/wk was associated with a reduced risk of mortality from all-causes.

              

            • Sex: Men and women

            PA assessment: Questionnaire for walking h/wk, divided into 3 groups

              

            USA

             

            • Age: ≥65 yr

            G1 = <1 hr/week

            Men

             
              

            Characteristics: Participants from a group health co-operative

            G2 = 1-4 hr/week

            • G1 = 1.00 (referent)

             

            Prospective cohort

              

            G3 = >4 hr/week

            • G2 = 0.78 (0.43-1.45)

             
                

            • G3 = 0.89 (0.49-1.62)

             

            D & B score = 12

               

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.50 (0.28-0.90)

             
                

            • G3 = 0.48 (0.25-0.83)

             
                

            Age 65-74 yr

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.81 (0.40-1.61)

             
                

            • G3 = 1.13 (0.60-2.15)

             
                

            Age ≥75 yr

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.63 (0.37-1.08)

             
                

            • G3 = 0.46 (0.25-0.84)

             
                

            High functioning

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.73 (0.38-1.41)

             
                

            • G3 = 0.89 (0.48-1.65)

             
                

            Limited functioning

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.60 (0.34-1.05)

             
                

            • G3 = 0.51 (0.28-0.92)

             

            Lam et al 2004 [192]

            To investigate the relationship LTPA and mortality in Hong Kong.

            • n = 24,079 cases (13,778 men; 10,301 women);

            10 years prior

            Multivariate adjusted OR (95% CI) by LTPA

            The data confirm and extend previous findings in Caucasian populations on the association between LTPA and longevity.

               

            PA assessment:

            Men

             

            Hong Kong

             

            • n = 13,054 controls (3,918 men; 9,136 women)

            Questionnaire for LTPA, divided into 3 groups

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.60 (0.54-0.67)

             

            Case-Control

               

            • G3 = 0.66 (0.60-0.73)

             
              

            • Sex: Men and women

            G1 = <1 times per month

              

            D & B score = 12

             

            • Age: ≥35 yr

             

            Women

             
              

            • Characteristics: All ethnic Chinese

            G2 = 1-3 times per month

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.81 (0.74-0.88)

             
               

            G3 = ≥4 times per month

            • G3 = 0.71 (0.66-.077)

             

            Lan et al 2006 [193]

            To investigate the relationship between exercise and all-cause mortality.

            • n = 2,113 (1,081 men; 1,032 women)

            Baseline and 2 year follow-up

            • 197 deaths

            Older persons are recommended to expend at least 1000 kcal/wk through regular exercise for mortality reduction.

              

            • Sex: Men and women

             

            HR (95% CI) by LTPA frequency

             

            Taiwan

             

            • Age: ≥65 yr

            PA assessment: Questionnaire for LTPA (frequency/wk)

              

            Prospective cohort

             

            • Characteristics: Non-institutionalized elders

             

            Adjusted for age and sex

            Protection of exercise against death also increases with the number of activities.

               

            G1 = Sedentary

            • G1 = 1.00 (referent)

             
              

            • Taiwan National Health Interview Survey

            G2 = 1 time/wk

            • G2 = 0.49 (0.36-0.67)

             

            D & B score = 13

              

            G3 = ≥2 times/wk

            • G3 = 0.20 (0.09-0.46)

             
                

            Trend p = <0.001

             
               

            Questionnaire for EE (kcal/wk), divided into 5 groups:

            Multivariate adjusted

             
                

            • G1 = 1.00 (referent)

             
               

            G1 = Sedentary

            • G2 = 0.70 (0.50-0.98)

             
               

            G2 = <500

            • G3 = 0.35 (0.15-0.82)

             
               

            G3 = 500-999

            Trend p = 0.014

             
               

            G4 = 1000-1999

              
               

            G5 = ≥2000

              
                

            HR (95% CI) by EE

             
                

            Adjusted for age and sex

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.64 (0.41-1.01)

             
                

            • G3 = 0.55 (0.35-0.85)

             
                

            • G4 = 0.30 (0.17-0.53)

             
                

            • G5 = 0.24 (0.12-0.48)

             
                

            Trend p <0.001

             
                

            Multivariate adjusted

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.80 (0.49-1.30)

             
                

            • G3 = 0.74 (0.46-1.17)

             
                

            • G4 = 0.50 (0.27-0.90)

             
                

            • G5 = 0.43 (0.21-0.87)

             
                

            Trend p = 0.043

             

            Laukkanen et al 2001 [194]

            To examine the relationship between maximal oxygen uptake and overall mortality.

            • n = 1,294

            Baseline and 10.7 year follow-up

            • 124 deaths

            PF has a strong, graded, inverse association with overall mortality.

              

            • Sex: Men

             

            Adjusted RR (95% CI) by quartile

             

            Finland

             

            • Age: 42.0-61.3 yr (mean 52.1)

               
              

            • Characteristics: Men free from CVD, COPD, and cancer at baseline

            PF assessment: Exercise tolerance test, 4 groups by maximal oxygen uptake (ml/kg/min)

              

            Prospective cohort

               

            Maximal oxygen uptake

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 1.47 (0.71-3.01)

             

            D & B score = 14

               

            • G3 = 2.79 (1.44-5.39)

             
               

            G1 = >37.1

            • G4 = 3.85 (2.02-7.32)

             
               

            G2 = 32.3-37.1

            Linear trend p = <0.001

             
               

            G3 = 27.6-32.2

              
               

            G4 = <27.6

            Test duration

             
                

            • G1 = 1.00 (referent)

             
               

            Test duration (min)

            • G2 = 2.22 (1.08-4.55)

             
               

            G1 = >11.2

            • G3 = 2.23 (1.11-4.49)

             
               

            G2 = 9.6-11.2

            • G4 = 3.94 (2.01-7.74)

             
               

            G3 = 8.2-9.5

            Linear trend p<0.001

             
               

            G4 = <8.2

              

            Lee and Paffenbarger 2000 [195]

            To compare various levels of PA with mortality.

            • n = 13,485

            Baseline and 15 year follow-up

            • 2,539 deaths

            The study provides some support for recommendations that emphasize MPA. A benefit of VPA is also evident.

              

            • Sex: Men

               
              

            • Age: Mean 57.5 yr

             

            RR (95% CI)

             
              

            • Characteristics: Men who matriculated as undergraduates in 1916-1950

            PA assessment:

            • G1 = 1.00 (referent)

             

            USA

              

            Questionnaires for LTPA index (including walking, stair climbing, sports and recreational activity),

            • G2 = 0.80 (0.72-0.88)

             
                

            • G3 = 0.74 (0.65-0.83)

             

            Prospective cohort

               

            • G4 = 0.80 (0.69-0.93)

             
              

            • The Harvard Alumni Health Study

             

            • G5 = 0.73 (0.64-0.84)

             
                

            Trend p = <0.001

             

            D & B score = 12

              

            5 groups (kJ/wk)

              
               

            G1 = <4200

              
               

            G2 = 4200-8399

              
               

            G3 = 8400-12599

              
               

            G4 = 12600-16799

              
               

            G5 = ≥ 16800

              

            Lee et al 1995 [196]

            To examine the independent association of vigorous and non-vigorous PA with longevity.

            • n = 17,321

            Follow-up 22-26 years

            • 3,728 deaths

            There is a graded inverse relationship between PA and mortality. Vigorous, but not non-vigorous activities are associated with longevity.

              

            • Sex: Men

               
              

            • Age: Mean 46 yr

            PA assessment: Questionnaires for EE (kJ/wk), quintiles

            RR (95% CI) by EE (kJ/wk)

             

            USA

             

            • Characteristics: Harvard University alumni, without self-reported physician diagnosed cardiovascular disease, cancer or chronic obstructive pulmonary disease

             

            Q1= 1.00 (referent)

             
                

            • Q2 = 0.94 (0.86--1.04)

             

            Prospective cohort

              

            Q1 = ≤ 630

            • Q3 = 0.95 (0.86--1.05)

             
               

            Q2 = 630-1680

            • Q4 = 0.91 (0.83 - 1.01)

             
               

            Q3 = 1680-3150

            • Q5 = 0.91 (0.82-1.00)

             

            D & B score = 12

              

            Q4 = 3150-6300

              
               

            Q5 = >6300

            RR (95% CI) by EE (Vigorous activity, kJ/wk)

             
                

            • Q1 = 1.00 (referent)

             
              

            • The Harvard Alumni Health Study

             

            • Q2 = 0.88 (0.82-0.96)

             
                

            • Q3 = 0.92 (0.82-1.02)

             
                

            • Q4 = 0.87 (0.77-0.99)

             
                

            • Q5 = 0.87 (0.78-0.97)

             

            Lee et al 2004 [197]

            To investigate the effect of various PA patterns on all-cause mortality.

            • n = 8,421

            Baseline 1988 and follow-up 1993

            • 1,234 deaths

            The results suggest that regular PA generating 1000 kcal/wk or more should be recommended for lowering mortality rates. Among those with no major risk factors, even 1-2 episodes per week generating 1000 kcal or more can postpone mortality.

              

            • Sex: Men

               
              

            • Age: Mean 66 yr

             

            Age adjusted RR (95% CI) by PA pattern

             

            USA

             

            • Characteristics: Participants free of major chronic disease

            PA assessment: Questionnaire for PA (kcal/wk), 4 groups

              
                

            • G1 = 1.00 (referent)

             

            Prospective cohort

               

            • G2 = 0.75 (0.63-0.90)

             
               

            G1 = <500

            • G3 = 0.82 (0.63-1.07)

             
              

            • The Harvard Alumni Health Study

            (Sedentary)

            • G4 = 0.61 (0.53-0.69)

             

            D & B score = 11

              

            G2 = 500-999

              
               

            (Insufficiently active)

            Multivariate adjusted

             
               

            G3 = ≥ 1000

              
               

            (Weekend warrior)

            • G1 = 1.00 (referent)

             
               

            G4 = Regularly active

            • G2 = 0.75 (0.62-0.91)

             
                

            • G3 = 0.85 (0.65-1.11)

             
                

            • G4 = 0.64 (0.55-0.73)

             

            Leitzmann et al 2007 [198]

            To examine PA guidelines in relation to mortality.

            • n = 252,925 (142,828 male; 110,097 women)

            Baseline and 6 month follow-up

            • 7,900 deaths

            Following PA guidelines is associated with lower risk of death. Mortality benefit may also be achieved by engaging in less than recommended activity levels.

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire for MPA and VPA, 5 groups each MPA (h/wk)

            Multivariate adjusted RR (95% CI) according to activity

             
              

            • Age: 50-71 yr

             

            MPA

             

            Prospective cohort

             

            • Characteristics: Participants free of CVD, cancer or emphysema

             

            • G1 = 1.00 (referent)

             
              

            • The National Institute of Health-American Association of Retired Persons

             

            • G2 = 0.85 (0.79-0.93)

             
                

            • G3 = 0.79 (0.74-0.85)

             

            D & B score = 13

              

            G1 = sedentary

            • G4 = 0.76 (0.71-0.82)

             
               

            G2 = <1

            • G5 = 0.68 (0.63-0.74)

             
               

            G3 = 1-3

            Trend p = <0.001

             
               

            G4 = 4-7

            VPA

             
               

            G5 = >7

              
               

            VPA (frequency/wk)

            • G1 = 1.00 (referent)

             
               

            G1 = inactive

            • G2 = 0.77(0.71-0.83)

             
               

            G2 = <1

            • G3 = 0.77 (0.72-0.82)

             
               

            G3 = 1-2

            • G4 = 0.68 (0.63-0.73)

             
               

            G4 = 3-4

            • G5 = 0.71 (0.66-0.77)

             
               

            G5 = ≥ 5

            Trend p = <0.001

             
               

            Cox proportional HR

              

            Leon et al 1997 [199]

            To examine the long-term association of LTPA and risk of death from coronary heart disease and all-causes.

            • n = 12,138

            16 year follow-up

            • 1,904 deaths

            The data suggest that a relatively small amount of daily moderate intensity LTPA can reduce premature mortality in middle-aged and older men at high risk for CHD.

              

            • Sex: Men

               
              

            • Age: 35-57 yr

            PA assessment: Minnesota LTPA questionnaire, categorized by frequency/month and average duration, deciles (min/d)

            Multivariate adjusted RR (95% CI) by deciles of LTPA

             

            USA

             

            • Characteristics: Men who at entry to the study were free of clinical evidence of CHD or other serious medical problems but were at the upper 10%-15% of a CHD probability score distribution derived from the FHS data

               

            Prospective cohort

               

            • D1 = 1.00 (referent)

             
                

            • D2-4 = 0.85 (0.73-0.99)

             
                

            • D5-7 = 0.87 (0.75-1.02)

             

            D & B score = 12

               

            • D8-10 = 0.83 (0.71-0.97)

             
               

            D1 = 4.9

              
               

            D2-4 = 22.7

              
               

            D5-7 = 53.9

              
               

            D8-10 = 140.4

              
              

            • Multiple Risk Factor Intervention Trial

            Cox proportional HR

              

            Lissner et al 1996 [200]

            To examine the relationship of OPA and LTPA on all-cause mortality in women.

            • n = 1,405

            Baseline and 20 year follow-up

            • 277 deaths

            Decreases in PA as well as low initial levels are strong risk factors for mortality.

              

            • Sex: Women

               
              

            • Age: 38-60 yr

             

            RR (95% CI) by LTPA

             

            Sweden

             

            • Characteristics: Free from major disease at baseline

            PA assessment: Questionnaire for OPA and LTPA, 3 groups

              
                

            20 year follow-up

             

            Prospective cohort

               

            LTPA during age 20-38 years

             
              

            • The Gothenburg Prospective Study of Women

             

            • Low = 1.00 (referent)

             
               

            G1 = Low

            • Med = 0.66 (0.34-1.26)

             

            D & B score = 10

              

            G2 = Medium

            • High = 0.46 (0.21-1.01)

             
               

            G3 = High

              
                

            LTPA during age 39-60 years

             
               

            Proportional hazard regression

            • Low = 1.00 (referent)

             
                

            • Med = 0.56 (0.35-0.90)

             
                

            • High = 0.44 (0.22-0.91)

             
                

            LTPA during the past 12 months

             
                

            • Low = 1.00 (referent)

             
                

            • Med = 0.56 (0.39-0.82)

             
                

            • High = 0.45 (0.24-0.86)

             
                

            20 year follow-up

             
                

            OPA during age 20-38 years

             
                

            • Low = 1.00 (referent)

             
                

            • Med = 0.59 (0.18-1.87)

             
                

            • High = 0.50 (0.16-1.58)

             
                

            OPA during age 39-60 years

             
                

            • Low = 1.00 (referent)

             
                

            • Med = 0.66 (0.21-2.08)

             
                

            • High = 0.47 (0.14-1.52)

             
                

            OPA during the past 12 months

             
                

            • Low = 1.00 (referent)

             
                

            • Med = 0.28 (0.17-0.46)

             
                

            • High = 0.24 (0.14-0.43)

             

            Manini et al 2006 [201]

            To determine whether energy expenditure is associated with all-cause mortality in older adults.

            • n = 302 (150 men; 152 women)

            Mean follow-up of 6.15 years

            • 55 deaths

            Free-living activity EE was strongly associated with lower risk of mortality.

              

            • Sex: Men and women

             

            HR (95% CI) by tertiles of PA EE

             

            USA

             

            • Age: 70-82 yr

            PA assessment: Questionnaire, divided into tertiles of PA EE (kcal/d)

              

            Prospective cohort

             

            • Characteristics: High-functioning community dwelling elders

             

            Adjusted for age, sex, race and study site

             
               

            T1 = <521

            • T1 = 1.00 (referent)

             

            D & B score = 13

              

            T2 = 521-770

            • T2 = 0.63 (0.29-1.18)

             
               

            T3 = >770

            • T3 = 0.37 (0.15-0.76)

             
                

            Trend p = 0.009

             
                

            Adjusted for age, sex, race, study site, weight, height, percent body fat and sleep duration

             
                

            • T1 = 1.00 (referent)

             
                

            • T2 = 0.57 (0.30-1.09)

             
                

            • T3 = 0.31 (0.14-0.69)

             
                

            Trend p = 0.004

             
                

            Adjusted for age, sex, race, study site, self rated health, education, smoking, CVD, lung disease, diabetes, hip or knee osteoarthritis, osteoporosis, cancer and depression

             
                

            • T1 = 1.00 (referent)

             
                

            • T2 = 0.65 (0.33-1.28)

             
                

            • T3 = 0.33 (0.15-0.74)

             
                

            Trend p = 0.007

             

            Matthews et al 2007 [202]

            To determine the effects of exercise and non-exercise PA on mortality.

            • n = 67,143

            Baseline and an average of 5.7 year follow-up

            • 1,091 deaths

            Overall PA levels are an important determinant of longevity.

              

            • Sex: Women

               
              

            • Age: 40-70 yr

             

            RR (95% CI)

             

            China

             

            • Characteristics: Women without heart disease, stroke or cancer

               
               

            PA assessment: Interview to report (MET h/d), 4 groups Overall activity

            Multivariate adjustment

             

            Prospective cohort

               

            Overall activity (MET hr/d)

             
                

            • G1 = 1.00 (referent)

             
              

            • The Shanghai Women's Health Study

             

            • G2 = 0.81 (0.69-0.96)

             

            D & B score = 12

              

            G1 = ≤ 9.9

            • G3 = 0.67 (0.57-0.80)

             
               

            G2 = 10.0-13.6

            • G4 = 0.61 (0.51-0.73)

             
               

            G3 = 13.7-18.0

            Trend p = 0.000

             
               

            G4 = ≥ 18.1

              
                

            Adult exercise (MET hr/d)

             
               

            Adult exercise

            • G1 = 1.00 (referent)

             
               

            G1 = 0

            • G2 = 0.84 (0.74-0.96)

             
               

            G2 = 0.1-3.4

            • G3 = 0.77 (0.59-0.99)

             
               

            G3 = 3.5-7.0

            • G4 = 0.64 (0.36-1.14)

             
               

            G4 = ≥ 7.1

            Trend p = 0.008

             
               

            Cox proportional hazard models

              

            Menotti and Seccareccia 1985 [203]

            To investigate the relationship between OPA and all-cause mortality.

            • n = 99,029

            Baseline and 5 year follow-up

            • 2,661 deaths

            The results suggest that PA may play a role in the prediction of fatal events.

              

            • Sex: Men

               
              

            • Age: 40-59 yr

               
              

            • Characteristics: Men employed on the Italian railway system

            PA assessment: Questionnaire Men at risk classified by 3 levels of PA and 3 levels of job responsibility, combined to create 8 groups of PA-job responsibility

            Age adjusted death rates per 1000 over 5 years classified by PA only

             

            Italy

               

            • Sedentary = 26.20

             

            Prospective cohort

               

            • Moderate = 27.05

             
                

            • Heavy = 27.35

             

            D & B score = 12

               

            Age adjusted death rates per 1,000 over 5 years classified by PA and job responsibility

             
               

            G1 = sedentary -- low

            • G1 = 30.00

             
               

            G2 = sedentary -- med

            • G2 = 25.20

             
               

            G3 = sedentary -- high

            • G3 = 25.80

             
               

            G4 = moderate -- low

            • G4 = 26.30

             
               

            G5 = moderate -- med

            • G5 = 28.50

             
               

            G6 = moderate -- high

            • G6 = 25.80

             
               

            G7 = heavy -- low

            • G7 = 26.90

             
               

            G8 = heavy -- med

            • G8 = 30.80

             

            Mensink et al 1996 [204]

            To compare various indices for PA and their association with cardiovascular risk factors as well as total and CVD mortality.

            • n = 15,436 (7,689 men; 7797 women)

            5-8 year follow-up

            Incidence of all-cause mortality and PA

            An inverse relation of PA and total mortality.

            Germany

             

            • Sex: Men and women

            PA assessment: Questionnaire Total activity, 3 groups

            Adjusted RR (95% CI)

             
              

            • Age: 25-69 yr

               

            Prospective cohort

             

            • Characteristics: Participants from communities in Western Germany

             

            Total activity, men

             
               

            G1 = Low

            • G1 = 1.00 (referent)

             
               

            G2 = Moderate

            • G2 = 0.56 (0.30-1.04)

             

            D & B score = 12

              

            G3 = High

            • G3 = 0.78 (0.42-1.44)

             
                

            Total activity, women

             
               

            LTPA, 3 groups

            • G1 = 1.00 (referent)

             
               

            G1 = Low

            • G2 = 1.24 (0.60-2.58)

             
               

            G2 = Moderate

            • G3 = 1.29 (0.58-2.85)

             
               

            G3 = High

              
               

            Conditioning activity, 3 groups

            LTPA, men

             
                

            • G1 = 1.00 (referent)

             
               

            G1 = No activity

            • G2 = 0.61 (0.35-1.05)

             
               

            G2 = Moderate

            • G3 = 0.79 (0.48-1.31)

             
               

            G3 = High

            LTPA, women

             
                

            • G1 = 1.00 (referent)

             
               

            Sports activity, 4 groups

            • G2 = 0.94 (0.51-1.75)

             
                

            • G3 = 0.81 (0.44-1.49)

             
               

            G1 = no sports

              
               

            G2 = <1 hour

            Conditioning activity, men

             
               

            G3 = 1-2 hours

            • G1 = 1.00 (referent)

             
               

            G4 = >2 hours

            • G2 = 0.76 (0.44-1.34)

             
                

            • G3 = 0.67 (0.36-1.25)

             
                

            Conditioning activity, women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.38 (0.13-1.06)

             
                

            • G3 = 0.80 (0.42-1.54)

             
                

            Sports Activity, men

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.49 (0.26-0.95)

             
                

            • G3 = 0.57 (0.30-1.09)

             
                

            • G4 = 0.36 (0.16-0.79)

             
                

            Sports activity, women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.38 (0.12-1.23)

             
                

            • G3 = 0.52 (0.23-1.17)

             
                

            • G4 = 0.28 (0.07-1.17)

             

            Morgan and Clarke 1997 [205]

            To assess the value of broadly based customary PA scores in predicting 10-year mortality in elderly people.

            • n = 1,042 (407 men; 635 women)

            10 year follow-up

            Incidence of all-cause mortality and PA

            A wide range of customary or habitual PA, can provide indices showing both cross sectional and predictive validity for 10 year mortality.

              

            • Sex: Men and women

            PA assessment: Questionnaire for PA, 3 groups

              

            UK

             

            • Age: ≥65 yr

             

            HR (95% CI)

             
              

            • Characteristics: British elders

             

            Men

             

            Prospective cohort

              

            G1 = Low

            • G1 = 1.59 (1.12-2.25)

             
              

            • Nottingham Longitudinal Study of Activity and Aging

            G2 = Intermediate

            • G2 = 1.35 (0.96-1.89)

             
               

            G3 = High

            • G3 = 1.00 (referent)

             

            D & B score = 12

               

            Women

             
                

            • G1 = 2.07 (1.53-2.79)

             
                

            • G2 = 1.53 (1.12-2.09)

             
                

            • G3 = 1.00 (referent)

             

            Myers et al 2002 [206]

            To compare PF and PA levels with all-cause mortality.

            • n = 6,213

            Baseline and mean 6.2 ± 3.7 year follow-up

            • 1,256 deaths

            Exercise capacity is a more powerful predictor of mortality among men than other established risk factors for CVD.

              

            • Sex: Men

               
              

            • Age: Mean 59 ± 11 yr

             

            Age adjusted RR (95% CI) by quintile

             

            USA

             

            • Characteristics: Participants with a normal exercise test result (n = 2,534) and participants with an abnormal exercise test or CVD or both (n = 3,679)

               
               

            PF assessment: Treadmill test for VO2 peak, divided into quintiles (METs)

            • Q1 = 4.5 (3.0-6.8)

             

            Prospective cohort

               

            • Q2 = 2.4 (1.5-3.8)

             
                

            • Q3 = 1.7 (1.1-2.8)

             
                

            • Q4 = 1.3 (0.7-2.2)

             

            D & B score = 12

              

            Q1 = Lowest level

            • Q5 = 1.00 (referent)

             
               

            1.0-5.9

              
               

            Q2

              
               

            Q3

              
               

            Q4

              
               

            Q5 = Highest level

              
               

            ≥13.0

              

            Ostbye et al 2002 [207]

            To analyze the effect of smoking and other modifiable risk factors on ill health, defined in a multidimensional fashion.

            • n = 12,956

            6 year follow-up

            • 782 deaths

            Quitting smoking and increasing exercise levels are the lifestyle interventions most likely to improve overall health.

              

            • Sex: Men and women

               
              

            • Age: 50-60 yr

            PA assessment: Questionnaire for PA, 4 groups

            Incidence of all-cause mortality and PA

             

            USA

             

            • Characteristics: Participants from the Health and Retirement Study (HRS) only

               

            Prospective cohort

              

            G1 = Sedentary

            Death rates (95% CI) per 1000 population/yr

             
               

            G2 = Light

              
               

            G3 = Moderate

            • G1 = 20.6 (17.8-24.0)

             

            D & B score = 13

              

            G4 = Heavy

            • G2 = 9.1 (8.1-9.5)

             
                

            • G3 = 8.3 (7.5-9.2)

             
                

            • G4 = 4.4 (3.5-5.6)

             

            Paffenbarger et al 1994 [208]

            To study the adoption or maintenance of PA and other optional lifestyle patterns for their influence on mortality rates of Harvard College alumni.

            • n = 14,786

            Follow-up between

            • 2,343 deaths

            Adopting a physically active lifeway delays mortality and extends longevity.

              

            • Sex: Men

            1977 and 1988

              
              

            • Age: 45-84 yr (in 1977)

             

            RR (95% CI) of mortality according to PA

             

            USA

              

            PA assessment: Questionnaire for blocks walked daily, stairs climbed daily and type, frequency and duration of weekly sports and recreational activities

              
              

            Characteristics: Harvard College alumni

               

            Prospective cohort

               

            Physical activity index (kcal/wk)

             
                

            • G1 = 1.00 (referent)

             

            D & B score = 14

               

            • G2 = 1.13 (1.01-1.26)

             
                

            • G3 = 0.72 (0.64-0.82)

             
                

            • G4 = 0.77 (0.69-0.85)

             
               

            Physical activity index (kcal/wk) Sports and recreational activities were scored according to intensity and duration

            Walking (km/wk)

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 1.21 (1.08-1.35)

             
                

            • G3 = 0.94 (0.83-1.07)

             
                

            • G4 = 0.89 (0.78-1.01)

             
                

            Moderately vigorous sports play (METs)

             
               

            Light < 4.5 METs

              
               

            Moderate ≥ 4.5 METs

              
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 1.11 (0.93-1.33)

             
                

            • G3 = 0.73 (0.65-0.81)

             
                

            • G4 = 0.72 (0.64-0.80)

             
                

            Adjusted for potential confounding influences

             

            Richardson et al 2004 [209]

            To investigate the impact of a sedentary lifestyle on all-cause mortality.

            • n = 9,611 (4,642 men; 4,969 women)

            Baseline (1992) and 8 year follow-up

            • 810 deaths

            A sedentary lifestyle is associated with a higher risk of death in pre- retirement aged adults.

              

            • Sex: Men and women

             

            OR (95% CI)

             

            USA

             

            • Age: 51-61 yr

            PA assessment: Questionnaire for PA, 3 groups:

            • G1 = 1.00 (referent)

             

            Prospective cohort

             

            • Characteristics: Participants born between 1931-1941 and who not institutionalized in 1992

             

            • G2 = 0.64 (0.52-0.81)

             
               

            G1 = Sedentary

            • G3 = 0.62 (0.44-0.85)

             
               

            G2 = occasional or light

            p = 0.01

             

            D & B score = 13

              

            G3 = Regular MVPA

              
              

            • Health and Retirement Study

               

            Rockhill et al 2001 [210]

            To determine the association between recreational PA and mortality in women.

            • n = 80,348

            Baseline (1980) and follow-up between 1982-1996

            • 4,871 deaths

            People who are more physically active are at reduced mortality risk relative to those who are less active.

              

            • Sex: Women

               
              

            • Age: 30-55 yr

             

            Multivariate adjusted RR (95% CI) by (hr/wk)

             

            USA

             

            • Characteristics: Free from CVD or cancer at baseline

               
              

            • Nurses Health Study

            PA assessment: Questionnaire in 1980 and up-dated every 2- 4 years, 5 groups of PA (hr/wk)

            • G1 = 1.00 (referent)

             

            Prospective cohort

               

            • G2 = 0.82 (0.76-0.89)

             
                

            • G3 = 0.75 (0.69-0.81)

             
                

            • G4 = 0.74 (0.68-0.81)

             

            D & B score = 11

               

            • G5 = 0.71 (0.61-0.82)

             
                

            p<0.001

             
               

            G1 = <1

              
               

            G2 = 1-1.9

              
               

            G3 = 2-3.9

              
               

            G4 = 4-6.9

              
               

            G5 = ≥7

              

            Rosengren and Wilhelmsen 1997 [211]

            To investigate the effect of OPA and LTPA on risk of death.

            • n = 7,142

            Baseline (1970-1973) and 20 year follow-up

            • 2,182 deaths

            The study demonstrates the protective effect of LTPA on mortality.

              

            • Sex: Men

               
              

            • Age: 47-55 yr

             

            Unadjusted RR (95% CI)

             
              

            • Characteristics: Without symptomatic CHD

            PA assessment: Postal questionnaires, 3 groups:

            • G1 = 1.00 (referent)

             

            Sweden

               

            • G2 = 0.74 (0.68-0.82)

             
                

            • G3 = 0.73 (0.68-0.79)

             

            Prospective cohort

              

            G1 = Sedentary

              
               

            G2 = Moderately active

            Multivariate adjustment

             
               

            G3 = Regular exercise

            • G1 = 1.00 (referent)

             

            D & B score = 13

               

            • G2 = 0.84 (0.77-0.93)

             
                

            • G3 = 0.83 (0.77-0.90)

             

            Schnohr et al 2003 [212]

            To assess the associations of regular LTPA and changes in LTPA with risk of death.

            • n = 7,023 (4,471 men; 5,676 women)

            18 year follow-up

            • 2,725 deaths

            Maintaining or adopting a moderate or high degree of PA was associated with lower risk of death.

              

            • Sex: Men and women

            PA assessment: Questionnaire, 9 groups

            Incidence of all-cause mortality and PA and changes in PA

             

            Denmark

             

            • Age: 20-79 yr

               
              

            • Characteristics: Participants from the Copenhagen City Heart Registered Population

               

            Prospective cohort

              

            G1 = Low--low

              
               

            G2 = Low--moderate

            Adjusted RR (95% CI)

             
               

            G3 = Low--high

            Men

             

            D & B score = 12

              

            G4 = Moderate- low

            • G1 = 1.00 (referent)

             
               

            G5 = Moderate-Moderate

            • G2 = 0.64 (0.49-0.83)

             
                

            • G3 = 0.64 (0.47-0.87)

             
               

            G6 = Moderate-high

            • G4 = 0.73 (0.56-0.96)

             
               

            G7 = High-low

            • G5 = 0.71 (0.57-0.88)

             
               

            G8 = High-moderate

            • G6 = 0.64 (0.51-0.81)

             
               

            G9 = High-high

            • G7 = 1.11 (0.76-1.62)

             
                

            • G8 = 0.66 (0.51-0.85)

             
                

            • G9 = 0.61 (0.48-0.76)

             
                

            Women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.75 (0.57-0.97)

             
                

            • G3 = 0.72 (0.50-1.05)

             
                

            • G4 = 0.70 (0.54-0.91)

             
                

            • G5 = 0.64 (0.52-0.79)

             
                

            • G6 = 0.58 (0.45-0.73)

             
                

            • G7 = 0.72 (0.48-1.07)

             
                

            • G8 = 0.61 (0.47-0.80)

             
                

            • G9 = 0.66 (0.51-0.85)

             

            Schnohr et al 2004 [213]

            To examine whether the relationship between established risk factors and mortality differs with socioeconomic status as measured by level of education.

            • n = 30,635 (16,236 men; 14,399 women)

            16 year follow-up

            • 10,952 deaths

            The study shows the strong predictive effect of PA on mortality is independent of education level.

              

            • Sex: Men and women

            Socioeconomic status assessment: level of education

            Incidence of all-cause mortality and PA stratified by years of education

             

            Denmark

             

            • Age: 20-93 yr

               
              

            • Characteristics: Participants from the Copenhagen City Heart Registered Population

               

            Prospective cohort

              

            PA assessment: Questionnaire

            Deaths <8 years of education

             

            D & B score = 12

               

            Men

             
               

            4 groups of PA

            G1 = 916

             
               

            G1 = none or very little

            G2 = 1693

             
               

            G2 = 2-4 h/wk of LPA

            G3 = 1012

             
               

            G3 = >4 h/wk of LPA or 2-4 h/wk of high level activity

            G4 = 67

             
               

            G4 = Competition level or >4 h/wk of hard level activity

            Women

             
                

            • G1 = 872

             
                

            • G2 = 1298

             
                

            • G3 = 346

             
                

            • G4 = 10

             
                

            8-11 years of education

             
                

            Men

             
                

            • G1 = 432

             
                

            • G2 = 1040

             
                

            • G3 = 616

             
                

            • G4 = 33

             
                

            Women

             
                

            • G1 = 363

             
                

            • G2 = 852

             
                

            • G3 = 268

             
                

            • G4 = 10

             
                

            >11 years of education

             
                

            Men

             
                

            • G1 = 104

             
                

            • G2 = 302

             
                

            • G3 = 182

             
                

            • G4 = 11

             
                

            Women

             
                

            • G1 = 48

             
                

            • G2 = 129

             
                

            • G3 = 61

             
                

            • G4 = 3

             

            Schnohr et al 2006 [214]

            To investigate the association between LTPA and mortality.

            • n = 4,894 (2,136 men; 2,758 women)

            Baseline (1976) and start of follow-up in 1981-1983 (to 2000)

            • 1,787 deaths

            Long-term moderate or high PA was associated with significantly lower mortality in men and women.

              

            • Sex: Men and women

             

            RR (95% CI)

             

            Denmark

             

            • Age: 20-79 yr

               
              

            • Characteristics: Healthy males and women

             

            Unadjusted

             

            Prospective cohort

              

            PA assessment: Survey for LTPA, 3 groups:

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.64 (0.56-0.73)

             
              

            • The Copenhagen City Heart Study

             

            • G3 = 0.56 (0.48-0.65)

             

            D & B score = 13

              

            G1 = Low

            Trend p < 0.001

             
               

            G2 = Mod

              
               

            G3 = High

            Multivariate adjustment

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.78 (0.68-0.89)

             
                

            • G3 = 0.75 (0.64-0.87)

             
                

            Trend p = 0.001

             

            Schooling et al 2006 [215]

            To examine how a Comprehensive assessment of baseline health status affects the relationship between obesity or PA and mortality.

            • n = 54,088 (17,849 men; 36,239 women)

            4.1 year follow-up

            • 3,819 deaths

            PA, which normally has a negative relationship with adiposity, had the largest impact on survival for the health states, with the strongest inverse relationship between BMI and mortality.

              

            • Sex: Men and women

            PA assessment: Interview for PA min/d, 3 groups

            Incidence of all-cause mortality and PA

             

            Hong Kong

             

            • Age: ≥ 65 yr

               

            Prospective cohort

             

            • Characteristics: Chinese elders

            G1 = None

            Adjusted HR (95% CI)

             
               

            G2 = ≤ 30 min/d

            • G1 = 1.00 (referent)

             
               

            G3 = ≥ 30 min/d

            • G2 = 0.83 (0.76-0.91)

             

            D & B score = 13

               

            • G3 = 0.73 (0.67-0.80)

             
                

            Trend p<0.001

             

            Sundquist et al 2004 [216]

            To study the association between varying levels of PA and all-cause mortality in the elderly.

            • n = 3,206 (1,414 men; 1,792 women)

            Baseline (1988-1989) and follow-up in 2000

            • 1,806 deaths

            Even occasional PA decreases the risk of mortality among elderly people.

              

            • Sex: Men and women

            PA assessment: Questionnaire for PA, 5 groups

            Age-adjusted HR (95% CI)

             

            Sweden

             

            • Age: ≥65 yr

             

            Men

             
              

            • Characteristics: Non-institutionalized elders

             

            • G1 = 1.00 (referent)

             

            Prospective cohort

               

            • G2 = 0.74 (0.62-0.87)

             
               

            G1 = none

            • G3 = 0.57 (0.44-0.73)

             
              

            The Swedish Annual Level-of-Living Survey (Statistics Sweden)

            G2 = occasionally

            • G4 = 0.51 (0.41-0.64)

             

            D & B score = 12

              

            G3 = once per week

            • G5 = 0.60 (0.44-0.82)

             
               

            G4 = twice per week

            Women

             
               

            G5 = vigorously at least twice per week

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.70 (0.59-0.82)

             
                

            • G3 = 0.59 (0.46-0.77)

             
               

            Cox proportional HR

            • G4 = 0.47 (0.35-0.62)

             
                

            • G5 = 0.54 (0.31-0.94)

             
                

            Men and women

             
                

            Multivariate adjustment

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.72 (0.64-0.81)

             
                

            • G3 = 0.60 (0.50-0.71)

             
                

            • G4 = 0.50 (0.42-0.59)

             
                

            • G5 = 0.60 (0.46-0.79)

             

            Talbot et al 2007 [217]

            To investigate how changes in LTPA affect all-cause mortality.

            • n = 2,092 (1,316 men; 776 women)

            Baseline in 1958 for males and in 1978 for females and an average follow-up of 21.2 ± 9.4 years for men and 10.2 ± 5.6 years for women

            • 628 deaths (538 male; 90 female)

            Greater declines in total and high-intensity LTPA are independent predictors of all-cause mortality.

              

            • Sex: Men and women

               

            USA

             

            • Age: 19-<90 yr

             

            RR (95% CI) for standard deviation of rate of change in LTPA

             

            Prospective cohort

             

            • Characteristics: Community residents, generally with above average income, high education and with good or excellent self related health

             

            (If RR is <1 then a SD increase is associated with decrease mortality. If RR is >1, then a SD increase is associated with increase in mortality)

             

            D & B score = 13

              

            PA assessment: Questionnaire for LTPA (METs min/24 h), 3 groups

              
              

            The Baltimore Longitudinal Study of Aging

            G1 = low

              
               

            G2 = medium

            Multivariate adjustment

             
               

            G3 = high

            Men <70 years

             
               

            Rate of change (ROC)

            • G1 = 0.96 (0.84-1.08)

             
                

            • G2 = 0.91 (0.79-1.04)

             
                

            • G3 = 0.42 (0.33-0.53)

             
                

            • ROC low = 0.90 (0.80-1.01)

             
                

            • ROC med = 1.01 (0.90-1.14)

             
                

            • ROC high = 0.78 (0.65-0.94)

             
                

            Men >70 years

             
                

            • G1 = 0.95 (0.82-1.10)

             
                

            • G2 = 0.89 (0.76-1.05)

             
                

            • G3 = 0.78 (0.62-0.97)

             
                

            • ROC low = 1.07 (0.93-1.24)

             
                

            • ROC med = 1.13 (1.00-1.27)

             
                

            • ROC high = 0.91 (0.75-1.12)

             
                

            Women <70 years

             
                

            • G1 = 0.75 (0.53-1.07)

             
                

            • G2 = 0.61 (0.36-1.03)

             
                

            • G3 = 0.80 (0.50-1.30)

             
                

            • ROC low = 1.02 (0.74-1.40)

             
                

            • ROC med = 1.38 (0.86-2.28)

             
                

            • ROC high = 0.90 (0.63-1.27)

             
                

            Women >70 years

             
                

            • G1 = 0.85 (0.63-1.15)

             
                

            • G2 = 0.78 (0.39-1.59)

             
                

            • G3 = 0.62 (0.32-1.22)

             
                

            • ROC low = 1.10 (0.85-1.42)

             
                

            • ROC med = 0.96 (0.46-2.03)

             
                

            • ROC high = 0.70 (0.40-1.22)

             

            Trolle-Lagerros et al 2005 [218]

            To quantify the effect of PA on overall mortality in younger women and to assess the effect of past versus current activity.

            • n = 99,099

            11.4 year follow-up

            • 1,313 deaths

            Current PA substantially reduces mortality among women. The association is observed even with low levels of PA and is accentuated with increased PA.

              

            • Sex: Women

               
              

            • Age: 30-49 yr

            PA assessment: Questionnaire using a 5 point scale, 5 groups

            Incidence of all-cause mortality and PA past and current

             

            Sweden and Norway

             

            • Characteristics: Participants from Norway and one region of Sweden

               

            Retrospective cohort

              

            G1 = Sedentary

            Adjusted HR (95% CI)

             
               

            G2 = Low

            PA at enrolment

             
               

            G3 = Moderate

            • G1 = 1.00 (referent)

             

            D & B score = 13

              

            G4 = High

            • G2 = 0.78 (0.61-1.00)

             
               

            G5 = Vigorous

            • G3 = 0.62 (0.49-0.78)

             
                

            • G4 = 0.58 (0.44-0.75)

             
                

            • G5 = 0.46 (0.33-0.65)

             
                

            Trend p<0.0001

             
                

            PA at age 30 yr

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.79 (0.55-1.15)

             
                

            • G3 = 0.90 (0.64-1.28)

             
                

            • G4 = 0.98 (0.68-1.42)

             
                

            • G5 = 0.96 (0.65-1.44)

             
                

            Trend p = 0.22

             
                

            PA at age 14 yr

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.95 (0.66-1.38)

             
                

            • G3 = 0.96 (0.69-1.34)

             
                

            • G4 = 0.88 (0.62-1.25)

             
                

            • G5 = 1.06 (0.75-1.51)

             
                

            Trend p = 0.62

             

            Villeneuve et al 1998 [219]

            To examine the relationship between PF, PA and all-cause mortality.

            • n = 14,442 (6,246 men; 8,196 women)

            Baseline (1981) and 7 year follow-up

            RR (95% CI) by EE, multivariate adjustment

            There was a reduction in mortality risk associated with even modest participation in activities of low intensity.

              

            • Sex: Men and women

               

            Canada

             

            • Age: 20-69 yr

            PA assessment: Questionnaire for EE (kcal/kg/day), 5 groups

            LTPA, men

             
              

            • Characteristics: Asymptomatic for CVD

             

            • G1 = 1.00 (referent)

             

            Prospective cohort

               

            • G2 = 0.81 (0.59-1.11)

             
                

            • G3 = 0.79 (0.54-1.13)

             
              

            Canadian Fitness Survey

            G1 = 0-<0.5

            • G4 = 0.86 (0.61-1.22)

             

            D & B score = 11

              

            G2 = 0.5-<1.5

            • G5 = 0.82 (0.65-1.04)*

             
               

            G3 = 1.5-<3.0

              
               

            G4 = ≥ 3.0

            Non vigorous LTPA, men

             
               

            G5 = ≥ 0.5

            • G1 = 1.00 (referent)

             
               

            PF levels:

            • G2 = 0.81 (0.56-1.17)

             
               

            Recommended

            • G3 = 0.70 (0.44-1.13)

             
               

            Minimum

            • G4 = 0.82 (0.53-1.27)

             
                

            • G5 = 0.78 (0.59-1.04)*

             
               

            Undesirable Refusal

              
                

            LTPA, women

             
               

            Multivariate Poisson regression analysis

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.94 (0.69-1.30)

             
                

            • G3 = 0.92 (0.64-1.34)

             
                

            • G4 = 0.71 (0.45-1.11)

             
                

            • G5 = 0.88 (0.68-1.04)*

             
                

            Non vigorous LTPA, women

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.97 (0.69-1.36)

             
                

            • G3 = 0.87 (0.57-1.33)

             
                

            • G4 = 0.72 (0.43-1.21)

             
                

            • G5 = 0.89 (0.67-1.17)*

             
                

            RR (95% CI) by fitness levels, adjusted for age, sex and smoking Recommended = 1.00 (referent)

             
                

            • Minimum = 1.02 (0.69-1.51)

             
                

            • Undesirable = 1.52 (0.72-3.18)

             
                

            • Refusal = 1.04 (0.45-2.39)

             

            Weller and Corey 1998 [220]

            To study the relationship between PA and mortality in women.

            • n = 6,620

            Baseline and 7 year follow-up

            • 449 deaths

            PA is inversely associated with risk of death in women.

              

            • Sex: Women

               
              

            • Age: ≥;30 yr

             

            OR (95% CI)

             

            Canada

             

            • Characteristics: Without known heart disease

            PA assessment: Questionnaires for: EE (kcal/kg/d), quartiles

              
              

            • Canadian Fitness Survey

             

            EE (kcal/kg/d)

             

            Prospective cohort

               

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 0.91 (0.66-1.25)

             
               

            Q1 = lowest

            • Q3 = 0.94 (0.72-1.23)

             

            D & B score = 11

              

            Q2 =

            • Q4 = 0.89 (0.67-1.17)

             
               

            Q3 =

              
               

            Q4 = highest

            LTPA levels

             
               

            LTPA, 3 groups

            • G1 = 1.00 (referent)

             
               

            G1 = Sedentary

            • G2 = 0.63 (0.46-0.86)

             
               

            G2 = Mod

            • G3 = 0.76 (0.59-0.98)

             
               

            G3 = High

              
                

            Walking

             
               

            Walking, 3 groups

            • G1 = 1.00 (referent)

             
               

            G1 = < half the time

            • G2 = 0.64 (0.49-0.82)

             
               

            G2 = half the time

            • G3 = 0.64 (0.47-0.86)

             
               

            G3 = > half the time

              

            Yu et al 2003 [221]

            To examine the relationship between LTPA and all-cause mortality.

            • n = 1,975

            Baseline and 10 year follow-up

            • 252 deaths

            The study found a strong inverse association between heavy LTPA and all-cause mortality.

            UK

             

            • Sex: Men

               
              

            • Age: 49-64 yr

             

            Age adjusted HR (95% CI)

             
              

            • Characteristics: Without a history of CHD at baseline

            PA assessment: Questionnaire (Minnesota LTPA index, kcal/d), 3 group

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.73 (0.54-0.99)

             

            Prospective cohort

               

            • G3 = 0.74 (0.55-1.04)

             
                

            Trend p = 0.046

             

            D & B score = 11

              

            G1 = Light to no activity

            Multivariate adjusted

             
               

            G2 = Moderate activity

            • G1 = 1.00 (referent)

             
               

            G3 = Heavy activity

            • G2 = 0.79 (0.58-1.08)

             
                

            • G3 = 0.76 (0.56-1.04)

             
                

            Trend p = 0.083

             

            D & B score, Downs and Black quality score; PF, physical fitness; YR, years; RR, risk ratio; 95% CI, 95% confidence interval; PA, physical activity; VO2 peak, peak oxygen consumption; HR, hazard ratio; min/d, minutes per day; kcal/wk, kilocalories per week; LTPA, leisure-time physical activity; MET, metabolic equivalent; VO2 max, maximal oxygen consumption; OPA, occupational physical activity; CVD, cardiovascular disease; hr/wk, hours per week; MPA, moderate physical activity; kcal/kg/wk, kilocalories per kilogram per week; kJ/wk, kilojoules per week; EE, energy expenditure; G, groups; EE, energy expenditure; BMI, body mass index; C, class; kg/m2, kilogram by meters squared; HR, heart rate; BPM, beats per minute; MVPA, moderate to vigorous physical activity; OR, odds ratio; Q, quartile or quintile; RCT, randomized clinical trial; T, tertiles; TPA, total physical activity; VPA, vigorous physical activity; mL/kg/min, milliliters per kilogram per minute.

            We observed a mean 31% lower risk for all-cause mortality in the most active individuals. The median risk reduction was 32%. It is important to highlight that many of these studies included women, with sub-analyses that revealed similar risk reductions between sexes. Our findings are consistent with previous reports [15, 16, 2931]. The majority (90%) of the studies supported the health benefits of physical activity demonstrating a significant risk reduction in physically active individuals. The level of evidence would be considered to be a Level 2A based on the presence of overwhelming evidence from observational trials. The studies examined were generally of a good quality with a mean (and median) score of 12 out of 15 (range 10-14).

            A clear dose-response relationship was also observed with marked reductions in the risk for all-cause mortality occurring with relatively small increments in physical activity (Figure 3). To examine more closely the temporal relationship between physical activity and all-cause mortality we calculated the (unadjusted) relative risks associated with incremental levels of physical activity/fitness using the reported cases of all-cause mortality and the number of participants (per group) in each investigation. In some instances, we were required to calculate the number of participants based on the reported incidence rates and person years, or based on data obtained directly from the authors (2 investigations). We were not able to obtain this information in 18 investigations, and as such this analysis was restricted to the remaining 52 investigations. There was considerable variability in the methods of classifying the physical activity/fitness levels of the participants. Accordingly, Figure 3 illustrates the mean relative risk reduction according to three separate study types including those that subdivided participants into tertiles, quartiles and quintiles, respectively. This figure demonstrates clearly the dose-response relationship between physical activity and all-cause mortality. Collectively, the literature is consistent indicating that the current Canadian guidelines (approximately 4.2 MJ/wk, 1000 kcal/wk) are associated with a 20-30% lower risk for premature all-cause mortality, with greater health benefits with high volumes and/or intensities of activity. In our analyses it was apparent that the greatest differences in risk occurred between the lowest adjacent activity/fitness categories, suggesting that sedentary individuals can markedly reduce their risk for all-cause mortality with relatively minor increments in physical activity. This is consistent with the current messaging of Canada's physical activity guidelines.
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig3_HTML.jpg
            Figure 3

            Mean relative risk reduction in all-cause mortality across physical activity/fitness categories.

            The strength of the relationship between physical fitness and premature mortality has been well-established [6, 32, 33]. In our analyses there were greater risk reductions in studies that took objective measures of physical fitness. We observed an average risk reduction of approximately 45%, which was consistent between men and women. A risk reduction of greater than 50% was not uncommon in these studies. For instance, Myers et al. (2004) reported that being fit or physically active was associated with greater than 50% lower mortality risk in men. They also noted that a 4.2 MJ/wk (1000 kcal/wk) increase in physical activity, or a 1 metabolic equivalent (MET) higher physical fitness level was associated with a mortality benefit of around 20%. It is also important to highlight that longitudinal studies evaluating changes in physical activity or fitness have revealed a lower premature mortality risk [16, 3441]. As we previously reported, routine physical activity or elevated physical fitness also appears to reduce the risk for premature mortality in individuals with risk factors for chronic disease [42, 43].

            Implications

            Since the seminal work of Morris and colleagues (in the 1950s [44, 45]) and the early work of Paffenbarger (in the 1970s [46, 47]) there has been considerable research (especially epidemiological evidence) documenting the health benefits of engaging in routine physical activity and/or being physically fit [17, 48]. Both physical activity (a behaviour) and physical fitness (an attained state) appear to be related to health status in a dose-dependent fashion, with physical fitness demonstrating the strongest relationship [18, 19]. Numerous reports indicate that physical inactivity and/or low physical fitness are associated with an increased risk for chronic disease and premature all-cause and disease-specific mortality [2, 43, 4951]. Some of the most compelling research includes the relationship between physical activity/fitness and all-cause mortality. As demonstrated below and in Table 11 and Figure 1, this literature is extensive.

            The assessment of the relationship between all-cause mortality is complicated by the inclusion of deaths related to suicides, homicide, and accidents [18, 19, 52]. Nonetheless, the available evidence is incontrovertible; individuals who are habitually physically active and/or physically fit are at a markedly reduced risk for premature all-cause mortality [15, 16, 18, 19]. In Canada, physical inactivity is a major cause of premature mortality from diseases of the cardiovascular system (33.3%), cancers (29.1%), and type 2 diabetes (3.5%) [53]. Globally, physical inactivity has been linked with 2 million premature deaths per year, including 22% of cases of coronary heart disease, and 10-16% of cases of breast cancer, colon cancer, rectal cancer and type 2 diabetes [54]. As such, the promotion of the health benefits of physical activity is of paramount importance for the effective prevention of chronic disease and premature mortality on a national and international scale.

            In summary, there is a clear dose-response relationship between physical activity and premature all-cause mortality. Physically active individuals have an approximate risk reduction of 31% in comparison to physically inactive individuals. When objective measures of aerobic fitness are taken the risk reductions are even greater approximating 45%.

            Recommendation #1

            For a reduced risk for premature mortality, it is recommended that individuals should participate in 30 min or more of moderate to vigorous exercise on most days of the week. Greater health benefits appear to occur with higher volumes and/or intensities of activity. [Level 2, Grade A]

            Primary Prevention of Cardiovascular Disease

            In our systematic search of the literature, a total of 9408 citations were identified during the electronic database search (Figure 4). Of these citations, 5973 were identified in MEDLINE, 2561 in EMBASE, 193 in Cochrane, and 681 in the CINAHL/SportDiscus/PsychInfo search. A total of 923 duplicates were found, leaving a total of 8485 unique citations. A total of 8138 articles were excluded after scanning, leaving a total of 347 articles for full review. An additional 20 articles were added through cross-referencing. From these articles 319 were excluded after full review leaving 33 articles for inclusion in the systematic review. The reasons for exclusion included non-experimental studies (n = 45), only effect on cardiovascular disease risk factors (n = 115), did not report 3 levels of physical activity (n = 12), subjects less than 18 yr of age (n = 4), reviews, summaries, dissertations, thesis, and abstracts (n = 30), clinical population (n = 14), not on cardiovascular disease or did not fit definition of cardiovascular disease (n = 78), and other (n = 19). Therefore, a total of 49 articles were included in the systematic review of the literature regarding the relationship between physical activity and the incidence of cardiovascular disease.
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig4_HTML.jpg
            Figure 4

            Results of the Literature Search for Cardiovascular Disease.

            The majority of the studies included in our systematic review were prospective cohort investigations (Table 12). These studies involved a total of 726,474 participants; averaging 12,313 participants per study (range 680-88,393). There were a total of 34,815 reported cases of cardiovascular disease (ranging per study from 42-2,596). The total length of study follow-up for the prospective cohort studies averaged 14.1 yr (ranging from 2-29 yr). The articles were published over a 32 yr period ranging from 1975 to 2007. These studies involved large samples of men and women from regions throughout the world.
            Table 12

            Studies examining the relationship between physical activity and cardiovascular disease.

            Publication Country Study Design Quality Score

            Objective

            Population

            Methods

            Outcome

            Comments and Conclusions

            Paffenbarger and Hale 1975 [47]

            To evaluate the role of PA in reducing coronary mortality among longshoreman

            • n = 6,351

            22 years of follow up, or until reached the age of 75 yr

            RR (95% CI) Sudden death

            VPA is associated with reduced risk of coronary mortality, particularly sudden cardiac death.

            USA

             

            • Sex: Men

             

               • G1 = 1.00 (referent)

             
              

            • Age: 35-74 yr

             

               • G2 = 3.5

             
              

            • Characteristics: Longshoreman

            PA assessment: Energy and oxygen cost requirements of longshoring jobs

               • G3 = 2.8

             

            Prospective cohort

               

            Delayed death

             
                

               • G1 = 1.00 (referent)

             

            D & B score = 12

               

               • G2 = 1.4

             
               

            Activity level

               • G3 = 1.5

             
               

            G1 = Heavy (5.2-7.5 kcal/min)

            Unspecified death

             
               

            G2 = Moderate (2.4-5.0 kcal/min)

               • G1 = 1.00 (referent)

             
               

            G3 = Light (1.5-2.0 kcal/min)

               • G2 = 1.1

             
                

               • G3 = 1.6

             
               

            Outcome measure: Death from CHD

              

            Manson et al 2002 [56]

            To compare the roles of walking and vigorous exercise in the prevention of CV events in a large, ethnically diverse cohort of postmenopausal women.

            • n = 73,743

            Enrolment from 1994-98 Clinic visit for baseline screening,

               • Number of New Cases: 345

            Both walking and VPA are associated with substantial reductions in the incidence of CHD events.

            USA

             

            • Sex: Women

             

               • Total Number of CVD events: 1551

             
              

            • Age: 50-79 yr

               
              

            • Characteristics: Healthy, Post Menopausal

             

            Age adjusted RR (95% CI) Total exercise (MET-hr/wk)

             
               

            PA assessment: Questionnaire for: Total exercise (MET- hr/wk)

              

            Prospective cohort

              

            G1 = 0-2.4

               • G1 = 1.00 (referent)

             
              

            • Women's Health Initiative Observational Study

            G2 = 2.5-7.2

               • G2 = 0.73 (0.53-0.99)

             
               

            G3 = 7.3-13.4

               • G3 = 0.69 (0.51-0.95)

             

            D & B score = 12

              

            G4 = 13.5-23.3

               • G4 = 0.68 (0.50-0.93)

             
               

            G5 = ≥ 23.4

               • G5 = 0.47 (0.33-0.67)

             
                

            p = <0.001

             
                

            Walking (MET-hr/wk)

             
               

            Walking (MET-hr/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = None

               • G2 = 0.71 (0.53-0.96)

             
               

            G2 = 0.1-2.5

               • G3 = 0.60 (0.44-0.83)

             
               

            G3 = 2.6-5.0

               • G4 = 0.54 (0.39-0.76)

             
               

            G4 = 5.1-10.0

               • G5 = 0.61 (0.44-0.84)

             
               

            G5 > 10

            p = 0.004

             
               

            Time for VPA (min)

            Vigorous exercise

             
               

            G1 = None

               • G1 = 1.00 (referent)

             
               

            G2 = 1-60

               • G2 = 1.12 (0.79-1.60)

             
               

            G3 = 61-100

               • G3 = 0.56 (0.32-0.98)

             
               

            G4 = 101-150

               • G4 = 0.73 (0.43-1.25)

             
               

            G5 = >150

               • G5 = 0.58 (0.34-0.99)

             
                

            p = 0.008

             
               

            Outcome Measure: Incidence of CVD and CHD

              

            Wisloff et al 2006 [58]

            To study the association between the amount and intensity of exercise and CVD mortality.

            • n = 56,072 (27,143 men; 28,929 women)

            Length of follow-up: 16 ± 4 yr

               • Number of Cases: 1,603 male, 993 female

            Men and women who exercise to a moderate degree and spend less than the recommended energy (< 1000 kcal/wk) are at lower risk of dying from heart disease than those who never exercise.

            Norway

             

            • Sex: Men and women

            PA assessment: Questionnaire for LTPA, 4 groups

            Multivariate RR (95% CI)

             

            Prospective cohort

             

            • Age: ≥ 20 yr

             

            Men

             
              

            • Characteristics: Free form CVD

            Men

               • Q1 = 1.00 (referent)

             
               

            Q1 = None

               • Q2 = 0.66 (0.50-0.87)

             

            D & B score = 12

             

            • HUNT study

            Q2 = 1/wk >30 min high

               • Q3 = 0.83 (0.65-1.06)

             
               

            Q3 = 2-3/wk > 30 min high

               • Q4 = 0.77 (0.59-1.01)

             
               

            Q4 = ≥ 4/wk > 30 min high

            Women

             
                

               • Q1 = 1.00 (referent)

             
               

            Women

               • Q2 = 0.63 (0.31-1.29)

             
               

            Q1 = None

               • Q3 = 0.66 (0.32-1.34)

             
               

            Q2 = 1/wk ≤ 30 min low

               • Q4 = 0.86 (0.45-1.62)

             
               

            Q3 = 1/wk ≤ 30 min high

              
               

            Q4 = 2-3/wk ≤ 30 min low

              
               

            Outcome Measure: Ischaemic heart disease mortality

              
               

            Cox proportional HR

              

            Lee et al 2001 [59]

            To examine the relationship between PA (specifically walking) and CHD among women, including those at high risk for CHD.

            • n = 39,372

            Recruitment of Participants: Sept 1992-May 1995

               • Number of Cases: 244

            Even light to moderate activity is associated with lower CHD rates in women.

            USA and Puerto Rico

             

            • Sex: Women

               
              

            • Age: ≥ 45 yr

             

            Multivariate RR (95% CI) Time spent walking

             
              

            • Characteristics: Healthy

            PA assessment: Questionnaires Divided into 4 or 5 groups:

               • G1 = 1.00 (referent)

             
              

            • Women's Health Study

             

               • G2 = 0.86 (0.57-1.29)

            As little as 1 hour of walking per week predicted lower risk.

            Prospective cohort

               

               • G3 = 0.49 (0.28-0.86)

             
                

               • G4 = 0.48 (0.29-0.78)

             
                

            p = <0.001

             

            D & B score = 12

              

            Time spent walking

              
               

            G1 = No regular walking

            Walking pace

             
               

            G2 = 1-59 min/wk

               • G1 = 1.00 (referent)

             
               

            G3 = 1.0-1.5 h/wk

               • G2 = 0.56 (0.32-0.97)

             
               

            G4 = ≥ 2.0 h/wk

               • G3 = 0.71 (0.47-1.05)

             
               

            Walking pace (km/h)

               • G4 = 0.52 (0.30-0.90)

             
               

            G1 = No regular walking

            p = 0.02

             
               

            G2 = 3.2

              
               

            G3 = 3.2-4.7

              
               

            G4 = ≥ 4.8

            EE (kcal/wk)

             
                

               • Q1 = 1.00 (referent)

             
               

            EE (kcal/wk)

               • Q2 = 0.79 (0.56-1.12)

             
               

            G1 = 200

               • Q3 = 0.55 (0.37-0.82)

             
               

            G2 = 200-599

               • Q4 = 0.75 (0.50-1.12)

             
               

            G3 = 600-1499 and

            p = 0.03

             
               

            G4 = 1500 or more

              
                

            Energy expended VPA (kcal/wk)

             
               

            Energy expenditure for VPA (kcal/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = No vigorous, <200 kcal/wk

               • G2 = 0.65 (0.46-0.91)

             
               

            G2 = No vigorous, ≥ 200 kcal/wk

               • G3 = 1.18 (0.79-1.78)

             
                

               • G4 = 0.96 (0.60-1.55)

             
                

               • G5 = 0.63 (0.38-1.04)

             
               

            G3 = Vigorous, 1-199 kcal/wk

              
               

            G4 = Vigorous, 200-499 kcal/wk

              
               

            G5 = Vigorous, ≥ 500 kcal/wk

              

            Paffenbarger et al 1993 [67]

            To analyze changes in the lifestyle of Harvard Alumni and the associations of these changes to mortality.

            • n = 10,269

            Baseline measure in 1962 or 1967 with a follow up in 1977

            Alumni who increased their PA index to 2000 kcal or more per week had a 17% lower risk of death from CHD then those who were sedentary (p = 0.507)

            Moderately vigorous sports activity was associated with lower rates of death from CHD among middle aged and older men

              

            • Sex: Men

               
              

            • Age: 45-84 yr

               

            USA

             

            • Characteristics: Health, Harvard College Alumni

               

            Prospective cohort

              

            PA assessment: Mailed questionnaires included questions on type, duration, intensity, frequency of PA.

            Men who took up moderate took up moderately vigorous activity had a 41% lower risk than those who continued not to engage in such activity (p = 0.044)

             

            D & B score = 13

              

            Outcome Measure: CHD deaths between 1977 and 1985

              
               

            Cox proportional hazards model

              
               

            Poisson regression methods

              
               

            The Mantel extension of the Mantel-Haenszel test

              

            Haapanen et al 1997 [77]

            To examine the association between duration and intensity of LTPA and the risk of CHD.

            • n = 2,840 (1,500 men; 1,340 women)

            Length of Follow-up: 10 yrs

               • Incident Rates (per 1000 person-years) for CHD = 108 for men and 75 for women.

            Total EE had an inverse and independent association with risk of CHD in middle aged Finnish men but not among women.

            Finland

             

            • Sex: Men and women

            PA assessment: Questionnaire for LTPA EE (kcal/wk)

            Multivariate RR (95% CI) LTPA and CHD mortality

             

            Prospective cohort

             

            • Age: 35-63 yr

             

            Men

             
              

            • Characteristics: Healthy

            Men

               • G1 = 1.98

             
               

            G1 = 0-1100

               • G2 = 1.33

             

            D & B score = 13

              

            G2 = 1101-1900

               • G3 = 1.00 (referent)

             
               

            G3 = >1900

              
                

            Women

             
               

            Women

               • G1 = 1.25

             
               

            G1 = 0-900

               • G2 = 0.73

             
               

            G2 = 901-1500

               • G3 = 1.00 (referent)

             
               

            G3 = >1500

              
               

            Outcome Measure: CHD mortality

              
               

            Cox proportional HR

              

            Barengo et al 2004 [164]

            To investigate whether moderate or high LTPA are associated with a reduced CVD and all-cause mortality, independent of CVD risk factors and other forms of PA in men and women.

            • n = 31,677 (15,853 men; 16,824 women)

            20 year follow-up

               • Number of Cases (Men): 1,661

            Moderate and high levels of LTPA and OPA are associated with reduced CVD mortality.

               

            PA assessment: Questionnaire for LTPA and OPA, 3 groups

               • Number of Cases (Women): 778

             

            Finland

             

            • Sex: Men and women

             

            HR (95% CI) LTPA, men

             

            Prospective cohort

             

            • Age: 30-59

            G1 = Low activity

               • G1 = 1.00 (referent)

             
              

            • Characteristics: Participant from eastern and south-western Finland

            G2 = Moderate activity

               • G2 = 0.91 (0.82-1.00)

             

            D & B score = 14

              

            G3 = High activity

               • G3 = 0.83 (0.69-0.99)

             
                

            LTPA, women (referent)

             
                

               • G1 = 1.00

             
                

               • G2 = 0.83 (0.71-0.96)

             
                

               • G3 = 0.89 (0.68-1.18)

             
                

            OPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.75 (0.64-0.87)

             
                

               • G3 = 0.77 (0.69-0.87)

             
                

            OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.73 (0.60-0.88)

             
                

               • G3 = 0.77 (0.65-0.91)

             

            Bijnen et al 1998 [166]

            To describe the association between the PA pattern of elderly men and CHD mortality.

            • n = 802

            Length of Follow-up: 10

               • Number of Cases: 90

            PA did not show a protective effect on death from CHD.

              

            • Sex: Men

               
              

            • Age: 64-84 yr

            PA assessment: Questionnaire, divided into 3 groups

            RR (95% CI)

             

            Netherlands

             

            • Characteristics: Free from Serious Illness

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.63 (0.38-1.05)

             

            Prospective cohort

              

            G1 = Lowest

               • G3 = 0.85 (0.51-1.44)

             
              

            • Ethnicity: Dutch

            G2 = Middle

              
              

            • Zutphen Elderly Study

            G3 = Highest

              

            D & B score = 13

              

            Outcome Measure: CHD Mortality

              
               

            Cox Proportional HR

              

            Davey-Smith et al 2000 [174]

            To examine the association between two measures of physical activity (LTPA and usual walking pace) with cause specific mortality (CHD).

            • n = 6,702

            Length of Follow-up: 25 yrs

               • Number of Cases: 955

            Inverse associations of both LTPA and walking pace with mortality from CHD were seen.

              

            • Sex: Men

               
              

            • Age: 40-64 yr

             

            RR (95% CI) by walking pace

             

            England

             

            • Whitehall Study

            PA assessment: Questionnaire during examination for walking pace and LTPA

               • G1 = 1.45 (0.9-2.2)

             
                

               • G2 = 1.30 (1.1-1.6)

             

            Prospective cohort

               

               • G3 = 1.00 (referent)

             
                

            p < 0.01

             

            D & B score = 11

              

            Walking pace

            Multivariate RR (95% CI) by LTPA level

             
               

            G1 = Slower

               • G1 = 1.24 (1.0-1.5)

             
               

            G2 = Same

               • G2 = 0.94 (0.8-1.2)

             
               

            G3 = Faster

               • G3 = 1.00

             
                

            p < 0.05

             
               

            LTPA

              
               

            G1 = Inactive

              
               

            G2 = Moderate

              
               

            G3 = Active

              
               

            Outcome Measure: CHD Mortality

              
               

            Cox Proportional HR

              

            Eaton et al 1995 [175]

            To determine whether self reported PA predicts a decreased risk of CHD.

            • n = 8,463 (LTPA), 8,418 (OPA)

            Length of Follow-up: 21 yrs

               • Number of Cases: 709

            Baseline levels of self reported LTPA predicted a decreased rate of CHD.

                

            Age adjusted RR (95% CI) by LTPA level

             

            USA

             

            • Sex: Men

            PA assessment: Interview

               • G1 = 1.00 (referent)

             
              

            • Age: 40 yr

             

               • G2 = 0.79 (0.63-0.99)

             

            Prospective cohort

             

            • Characteristics: Healthy, free of CHD

            LTPA

               • G3 = 0.73 (0.59-0.89)

             
               

            G1 = Sedentary

               • G4 = 0.71 (0.52-0.98)

             
               

            G2 = Light

              

            D & B score = 11

             

            Ethnicity: Israeli

            G3 = Light Daily

            Age adjusted RR (95% CI) by OPA level

             
               

            G4 = Heavy

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.99 (0.75-1.18)

             
               

            OPA

               • G3 = 0.94 (0.78-1.12)

             
               

            G1 = Sitting

               • G4 = 0.87 (0.67-1.10)

             
               

            G3 = Walking

              
               

            G4 = Physical Labour

              
               

            Outcome Measure: CHD Death

              
               

            Cox Proportional HR

              

            Hillsdon et al 2004 [183]

            To examine whether a short, easily administered measure of PA is associated with the risk of death from all causes and specific causes.

            • n = 10,522 (4,929 men; 5,593 women)

            Length of Follow-up: > 10 yrs

               • Number of Cases: 155

            Self reported VPA is associated with the risk of future mortality.

                

            Multivariate RR (95% CI) by PA level

             

            UK

             

            • Sex: Men and women

            PA assessment: Questionnaire, 3 groups:

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.46 (0.19-1.12)

             

            Prospective cohort

             

            • Age: 35-64 yr

            G1 = Never / <1 time/month

               • G3 = 0.96 (0.53-1.75)

             
              

            • Characteristics: no history of chest pain

               
               

            G2 = <2 times/wk

              

            D & B score = 11

              

            G3 = ≥ 2 times/wk

              
               

            Outcome Measure: IHD mortality

              
               

            Cox proportional HR

              

            Leon et al 1997 [199]

            To study the relationship of PA to CHD in a well defined population at above average risk for CHD over a 16 yr observation period.

            • n = 12,138

            Follow up for 16 years

            Age Adjusted RR (95% CI)

            A relatively small amount (10-36 min/d) of daily moderate intensity LTPA can significantly reduce premature mortality from CHD in middle aged men at high risk for CHD.

            USA

             

            • Sex: Men

             

               • G1 = 1.00 (referent)

             
              

            • Age: 35-57 yr

            PA assessment: Questionnaire at baseline (Minnesota LTPA questionnaire), divided/grouped into deciles of LTPA (min/d)

               • G2 = 0.71 (0.56-0.91)

             
              

            • Characteristics: Free of CHD but in the upper 10-15% of a CHD probability risk score

             

               • G3 = 0.75 (0.59-0.96)

             
                

               • G4 = 0.69 (0.54-0.96)

             

            Prospective cohort

               

            Multivariate adjusted RR (95% CI)

             
                

               • G1 = 1.00 (referent)

             

            D & B score = 11

              

            G1 = D1: (0-9 min/d)

               • G2 = 0.75 (0.54-0.96)

             
              

            Multiple risk factor intervention trial

            G2 = D2-4: (10-36 min/d)

               • G3 = 0.81 (0.64-1.04)

             
               

            G3 = D5-7: (37-75 min/d)

               • G4 = 0.75 (0.59-0.96)

             
               

            G4 = D8-10: (76-359 min/d)

              
               

            Outcome Measure: CHD Mortality

              

            Rosengren et al 1997 [211]

            To examine the long term effect of OPA and LTPA on the risk of death from CHD.

            • n = 7,142

            Length of Follow-up: 20 yrs

            Number of Cases: 684

            There appears to be a protective effect of LTPA on CHD-related death.

              

            • Sex: Men

               
              

            • Age: 47-55 yr

             

            Multivariate RR (95% CI) for LTPA

             

            Sweden

             

            • Characteristics: Swedish men

            PA assessment: Questionnaire for LTPA, 3 groups

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.84 (0.71-1.00)

             

            Prospective cohort

               

               • G3 = 0.84 (0.73-0.96)

             
               

            G1 = Sedentary

              
               

            G2 = Moderately active

              

            D & B score = 13

              

            G3 = Regular exercise

              
               

            Outcome Measure: CHD death

              
               

            Proportional HR

              

            Schnohr et al 2006 [214]

            To describe the associations between different levels of LTPA and subsequent causes of death.

            • n = 4,894 (2,136 men; 2,758 women)

            Participants included in the study were only those whose PA levels did not change over 5 years

               • Number of Cases: 292

            There was an inverse and significant dose- response association between LTPA and CHD-related mortality.

                

            Adjusted RR (95% CI) Whole group

             

            Denmark

             

            • Sex: Men and women

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.71 (0.51-0.99)

             

            Prospective cohort

             

            Age: 20--79 yr

            PA assessment:

               • G3 = 0.56 (0.38-0.82)

             
              

            • Characteristics: Healthy

            Questionnaire LTPA

              

            D & B score = 12

             

            • Copenhagen City Heart Study

            G1 = <4 METS

            Men

             
               

            G2 = 4-6 METS

               • G1 = referent

             
               

            G3 = >6 METS

               • G2 = survived 4.9 yrs longer

             
                

               • G3 = survived 6.8 yrs longer

             
               

            Cox proportional HR

              
                

            Women

             
                

               • G1 = referent

             
                

               • G2 = survived 5.5 yrs longer

             
                

               • G3 = survived 6.4 yrs longer

             

            Weller et al 1998 [220]

            To examine the relationship between PA and mortality.

            • n = 6,620

            Length of Follow-up: 7 yrs

               • Number of Cases: 109

            LTPA is inversely associated with risk of fatal MI.

              

            • Sex: Women

               
              

            • Age: ≥ 30 yr

            PA assessment:

            OR (95% CI) by LTPA

             

            Canada

             

            • Characteristics: Canadian Women

            Questionnaire, 4 groups for LTPA (kcal/kg/day) and non-LTPA (kcal/kg/day)

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.61 (0.07-1.19)

             

            Prospective cohort

               

               • Q3 = 0.84 (0.52-1.37)

             
                

               • Q4 = 0.63 (0.36-1.09)

             

            D & B score = 9

              

            LTPA (kcal/kg/day)

            OR (95% CI) by non-LTPA

             
               

            Q1 = ≥ 0

               • Q1 = 1.00 (referent)

             
               

            Q2 = ≥ 0.1

               • Q2 = 0.71 (0.44-1.16)

             
               

            Q3 = ≥ 0.5

               • Q3 = 0.57 (0.33-0.97)

             
               

            Q4 = ≥ 1.6

               • Q4 = 0.49 (0.26-0.92)

             
               

            Non-LTPA (kcal/kg/day)

              
               

            Q1 = ≥ 0

              
               

            Q2 = ≥ 2.8

              
               

            Q3 = ≥ 5.9

              
               

            Q4 = ≥ 9.9

              
               

            Outcome Measure: Fatal MI

              
               

            Logistic regression analysis

              

            Yu et al 2003 [221]

            To examine the optimal intensity of LTPA to decrease the risk of CHD mortality in middle aged British men.

            • n = 1,975

            10 year follow-up

               • Number of Cases: 82

            Strong significant inverse relationship between heavy LTPA and CHD mortality.

              

            • Sex: Men

            PA assessment: Questionnaire (Minnesota LTPA questionnaire), 3 groups

            Multivariate adjusted HR (95% CI)

             
              

            • Age: 49-64 yr

             

               • G1 = 1.00 (referent)

             

            UK

             

            • Characteristics: Healthy, no previous history of CHD

             

               • G2 = 0.74 (0.44-1.25)

             
                

               • G3 = 0.55 (0.31-0.98)

             

            Prospective cohort

               

            p = 0.039

            Relationship was not significant for low- moderate intensity LTPA and OPA.

              

            • Caerphilly collaborative heart study

            Total activity level (kcal/day)

              

            D & B score = 11

              

            G1 = 0.0 - 161.6

              
               

            G2 = 161.8 - 395.3

              
               

            G3 = 395.5 - 2747.2

              
               

            Cox proportional HR

              

            Altieri et al 2004 [222]

            To assess the possible protective role of PA on CHD.

            • n = 985 (507 men; 478 women)

            PA assessment: Questionnaire for OPA, divided into quartiles

            Number of Cases: 507

            LTPA from 15-19 yrs as well as OPA from 30 - 39 yrs both have a significant inverse relationship with risk of non fatal acute MI.

                

            OR (95% CI) for CHD and OPA

             

            Italy

             

            • Sex: Men and women

            Q1 = lowest

               • Q1 = 1.00 (referent)

             
               

            Q2

               • Q2 = 0.63 (0.39-1.03)

             

            Case Control

             

            • Age: < 79 yr

            Q3

               • Q3 = 0.56 (0.35-0.90)

             
              

            • Characteristics: Case: Patients admitted to Hospital with non-fatal Acute MI. Controls: Patients admitted to hospital for acute condition unrelated to known or potential risk factors for acute MI

            Q4 = highest

               • Q4 = 0.57 (0.34-0.95)

             

            D & B score = 11

               

            p = 0.045

             
               

            Outcome Measure: Non Fatal acute MI

              
               

            Unconditional logistic regression

              

            Batty et al 2003 [223]

            To examine the relationship between physical activity and three mortality endpoints in healthy persons.

            • n = 6,474

            Length of Follow-up: 25 yr

               • Number of Cases: 837

            A suggestion that the symptomatic nature of ischemia appeared to modify the affects of

              

            • Sex: Men

             

               • Number of Dropouts: 158

             
              

            • Age: 40-64 yr

            PA assessment: Questionnaire for LTPA, divided into 3 groups:

              

            UK

             

            • Characteristics: British civil servants who underwent a resting ECG

             

            HR (95% CI) for CHD and LTPA

             
                

               • G1 = 1.14 (0.9-1.4)

            PA on total and CHD mortality.

            Prospective cohort

              

            G1 = Inactive

               • G2 = 0.94 (0.8-1.1)

             
               

            G2 = Moderate

               • G3 = 1.00 (referent)

             
               

            G3 = Active

              

            D & B score = 13

                 
               

            Outcome Measure: CHD mortality

              
               

            Cox Proportional HR

              

            Chen and Millar [224]

            To examine the potential protective effect of LTPA on the incidence of heart disease and depression.

            • n = 15,670

            Length of Follow-up: 2 yrs

            • 100 cases

            Regular and at least MPA can be beneficial to heart health.

              

            • Sex: Men and women

               
              

            • Age: ≥ 20 yr

            PA assessment: EE from self administered questionnaire, 4 groups (kcal/kg/day)

            Adjusted OR (95% CI)

             

            Canada

             

            • Characteristics: Healthy and free from heart disease

             

               • G1 = 5.0 (1.84-13.59)

             
                

               • G2 = 3.7 (1.26-10.67)

             

            Prospective cohort

               

               • G3 = 1.00 (referent)

             
               

            G1 = Sedentary

               • G4 = 1.3 (0.41-3.89)

             
               

            G2 = Light (<1.5)

              

            D & B score = 11

             

            National Population Health Survey

            G3 = Moderate (1.5-2.9)

              
               

            G4 = Active (≥ 3)

              
               

            Outcome Measure: CHD incidence

              
               

            Multiple logistic regression

              

            Conroy et al 2005 [225]

            To examine the relationship between 1) PA during young adulthood and middle age, and 2) PA during each time period and CHD during middle age and older women.

            • n = 37,169

            Length of Follow-up: 9 yrs

               • Number of Cases: 477

            PA during middle age predicts lower risk of CHD

              

            • Sex: Women

               
              

            • Age: ≥ 45 yr

             

            Multivariate RR (95% CI) Baseline PA and incidence of CHD

             

            US

             

            • Characteristics: Healthy women health professionals

            PA assessment: Questionnaire for EE (kcal/wk) and months/yr

              
              

            • Women's Health Study

             

               • G1 = 1.00 (referent)

             

            Cohort study

               

               • G2 = 0.62 (0.48-0.80)

             
                

               • G3 = 0.61 (0.48-0.79)

             

            D & B score = 11

              

            Baseline PA (kcal/wk)

               • G4 = 0.61 (0.46-0.81)

             
               

            G1 = <200

            p = <0.001

             
               

            G2 = 200-599

              
               

            G3 = 600-1499

            Past PA and incidence of CHD

             
               

            G4 = ≥ 1500

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.76 (0.57-1.02)

             
               

            Past PA

               • G3 = 0.95 (0.72-1.24)

             
               

            Months per year

               • G4 = 1.04 (0.78-1.39)

             
               

            G1 = 0

               • G5 = 0.81 (0.58-1.14)

             
               

            G2 = 1-3

              
               

            G3 = 4-6

              
               

            G4 = 7-9

              
               

            G5 = 10-12

              
               

            Outcome Measure: Incidence of CHD

              
               

            Cox proportional hazard regression

              

            Dorn et al 1999 [226]

            To examine the long-term relationships between total PA and mortality from all causes and CHD in the general population.

            • n = 1,461 (698 men; 763 women)

            Length of Follow-up: 29 years

               • Number of Cases: 109 men, 81 women

            PA favorably influences mortality risks in non- obese men and younger women.

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire

            Multivariate RR (95% CI) for PAI in non- obese men

             

            Prospective cohort

             

            • Age: 15-96 yr

             

               • 0.40 (0.19-0.88) for 1 kcal/kg/h

             
              

            • Characteristics:

            Outcome Measure: CHD

            Multivariate RR (95% CI) for PAI in obese men

             
              

            Healthy, free from CHD, diabetes, and Stroke.

            Mortality

               • 1.86 (0.86-4.03) for 1 kcal/kg/h

             

            D & B score = 11

                 
               

            Cox Proportional Hazard

              
               

            Ratio

            Multivariate RR (95% CI) for PAI in women < 60 yrs

             
              

            • Ethnicity: White.

             

               • 0.42 (0.11-1.52) for 1 kcal/kg/h

             
                

            Multivariate RR (95% CI) for PAI in women > 60 yrs

             
                

               • 1.78 (0.77-4.09) for 1 kcal/kg/h

             

            Folsom et al 1997 [227]

            To examine the association of PA at baseline with CHD incidence.

            • n = 13,999 (6,166 men; 7833 women)

            Length of Follow-up: 4-7 yrs

               • Number of Cases: 223 men, 97 women,

            No significant relationships.

                

            Multivariate RR (95% CI) LTPA, men

             

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire during home interview, divided into quartiles of LTPA and sports activity

              
                

               • Q1 = 1.00 (referent)

             

            Prospective cohort

             

            • Age: 45-64 yr

             

               • Q2 = 1.08 (0.75-1.55)

             
              

            • Characteristics: no CHD at baseline

             

               • Q3 = 0.83 (0.51-1.36)

             
                

               • Q4 = 0.89 (0.59-1.35)

             

            D & B score = 9

              

            Q1 = Low

              
              

            • Ethnicity: Black and non Black

            Q2

            LTPA, women

             
               

            Q3

               • Q1 = 1.00 (referent)

             
              

            • Atherosclerosis Risk in Communities Study

            Q4 = High

               • Q2 = 0.74 (0.42-1.31)

             
                

               • Q3 = 1.07 (0.55-2.09)

             
               

            Outcome Measure: CHD incidence Poisson Regression

               • Q4 = 0.64 (0.34-1.24)

             
                

            Multivariate RR (95% CI) Sports, men

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.15 (0.79-1.68)

             
                

               • Q3 = 1.03 (0.68-1.54)

             
                

               • Q4 = 0.83 (0.56-1.23)

             
                

            Sports, women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.99 (0.58-1.67)

             
                

               • Q3 = 0.64 (0.32-1.27)

             
                

               • Q4 = 0.72 (0.37-1.38)

             

            Fransson et al 2004 [228]

            To estimate the influence of LTPA and OPA on acute MI.

            • n = 4069 (2,742 men; 1,327 women)

            PA assessment: Questionnaire for LTPA, 5 groups

               • Number of Cases: 1,204 men, 550 women

            Exercise seems to reduce the risk of MI.

            Sweden

             

            • Sex: Men and Women

            G1 = Seldom

            OR (95% CI)

             
               

            G2 = Sometimes

              

            Case Control

             

            • Age: 45-70 yr

            G3 = 1×/wk

            LTPA, men

             
              

            • Characteristics: Cases: Diagnosed with acute MI

            G4 = 2-3×/wk

               • G1 = 1.00 (referent)

             

            D & B score = 12

              

            G5 = >3×/wk

               • G2 = 0.76 (0.61-0.95)

             
                

               • G3 = 0.67 (0.51-0.88)

             
                

               • G4 = 0.63 (0.49-0.83)

             
              

            • Stockholm Heart Epidemiology

            Questionnaire for total physical activity, 3 groups

               • G5 = 0.53 (0.38-0.73)

             
               

            G1 = Passive

              
               

            G2 = Somewhat active

            LTPA, women

             
               

            G3 = Active

               • G1 = 1.00 (referent)

             
               

            Questionnaire for sitting at work, 3 groups

               • G2 = 0.69 (0.49-0.98)

             
                

               • G3 = 0.38 (0.25-0.58)

             
               

            G1 = Less than half the time

               • G4 = 0.62 (0.38-1.01)

             
               

            G2 = About half the time

               • G5 = 0.31 (0.15-0.66)

             
               

            G3 = More than half the time

            Total physical activity, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.66 (0.47-0.94)

             
               

            Outcome Measure: Acute MI

               • G3 = 0.46 (0.31-0.69)

             
                

            Total physical activity, women

             
               

            Conditional and unconditional logistics regression

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.34 (0.22-0.53)

             
                

               • G3 = 0.16 (0.07-0.37)

             
                

            Sitting at work, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.91 (0.73-1.15)

             
                

               • G3 = 0.90 (0.72-1.12)

             
                

            Sitting at work, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.77 (0.51-1.17)

             
                

               • G3 = 0.47 (0.31-0.69)

             

            Fransson et al 2006 [229]

            To evaluate whether LTPA compensates for the increased risk of acute MI associated with overweight and obesity.

            • n = 4069 (2,742 men; 1,327 women)

            PA Assessment: Questionnaire for LTPA, 3 groups

            Number of Cases: 1204 men, 550 women

            Regular LTPA seems to provide protection against MI and non- fatal MI.

                

            Multivariate OR (95% CI) for acute MI

             

            Sweden

             

            • Sex: Men and women

            G1 = Very little /occasional walks

            LTPA, men

             
                

               • G1 = 1.00 (referent)

             

            Case Control

             

            • Age: 45-70 yr

            G2 = Occasional / once per week

               • G2 = 0.70 (0.58-0.84)

             
              

            • Characteristics: Cases: had acute MI

             

               • G3 = 0.57 (0.46-0.71)

             

            D & B score = 12

              

            G3 = Twice per week or more

            LTPA, women

             
                

               • G1 = 1.00 (referent)

             
               

            Outcome measure: Acute MI

               • G2 = 0.52 (0.40-0.68)

             
                

               • G3 = 0.44 (0.30-0.65)

             
                

            Multivariate OR (95% CI) for non-fatal MI

             
               

            Conditional and unconditional logistics regression

            LTPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.79 (0.65-0.96)

             
                

               • G3 = 0.63 (0.50-0.79)

             
                

            LTPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.64 (0.48-0.86)

             
                

               • G3 = 0.58 (0.39-0.87)

             

            Haapanen-Niemi 2000 [230]

            To investigate the independent associations and the possible interaction of BMI LTPA and perceived physical performance and functional capacity with the risk of mortality.

            • n = 2,212 (1,090 men; 1,122 women)

            Length of Follow-up: 16 yrs

               • Number of Cases: 208 all cause deaths, 54% of those CVD. 73% of CVD deaths due to CHD

            Increase perceived PF is associated with a reduced risk of CHD mortality in men.

            Finland

             

            • Sex: Men and women

            PA assessment: Postal Survey

              
                

            Multivariate RR (95% CI)

             

            Prospective cohort

             

            • Age: 35-63 yr

            Total LTPA energy expenditure (kcal/wk)

            Total LTPA EE index and CHD mortality, men

             
              

            • Characteristics:

            Healthy

             

               • G1 = 1.00 (referent)

             
               

            G1 = High

               • G2 = 0.88 (0.44-1.76)

             

            D & B score = 13

             

            • Ethnicity:

            Finnish

            G2 = Moderate

               • G3 = 1.70 (0.90-3.21)

             
               

            G3 = Low

            p = 0.056

             
               

            Perceived physical fitness compared to age-mates

            Multivariate RR (95% CI) Perceived physical fitness, men

             
               

            G1 = Better

               • G1 = 1.00 (referent)

             
               

            G2 = Similar

               • G2 = 2.82 (1.06-7.46)

             
               

            G3 = Worse

               • G3 = 4.64 (1.56-13.84)

             
               

            Outcome Measure: CHD mortality

            p = 0.011

             
                

            Total LTPA EE index and CHD mortality, women

             
               

            Cox proportional HR

              
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.43 (0.16-1.16)

             
                

               • G3 = 1.17 (0.51-2.68)

             
                

            p = 0.046

             
                

            Multivariate RR (95% CI) Perceived physical fitness, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.82 (0.32-2.16)

             
                

               • G3 = 1.89 (0.57-6.27)

             
                

            p = 0.154

             

            Kannel et al 1986 [231]

            To examine the role of low levels of OPA and LTPA in the development of CV morbidity and mortality over the short and long term.

            • n = 1,166

            Length of Follow-up: 24 yrs

               • Number of Cases: 220 mortality, 371 morbidity

            Rate of CHD Mortality and Morbidity decreases with increased level of PA but no association was found with physical demand of work

              

            • Sex: Men

               
              

            • Age: 45-65 yr

               

            USA

             

            • Characteristics:

            PA assessment: Questionnaire during examination

            Cumulative 24 year age adjusted rate per 1000 people

             

            Prospective cohort

               

            24 hr PA index for LTPA CHD mortality

             
               

            PA index:

               • G1 = 255

             

            D & B score = 11

              

            G1 = <29

               • G2 = 184

             
               

            G2 = 30-34

               • G3 = 152

             
               

            G3 = >34

            p < 0.01

             
               

            Physical demand of work

            24 hr PA index for LTPA CHD incidence

             
               

            G1 = Sedentary

               • G1 = 414

             
               

            G2 = Light

               • G2 = 353

             
               

            G3 = Medium

               • G3 = 311

             
               

            G4 = Heavy

              
               

            Outcome Measure: CHD mortality and Morbidity

            Physical demand of work and CHD mortality

             
                

               • G1 = 216

             
               

            Cox proportional HR

               • G2 = 209

             
                

               • G3 = 169

             
                

               • G4 = 170

             
                

            Physical demand of work and CHD incidence:

             
                

               • G1 = 355

             
                

               • G2 = 405

             
                

               • G3 = 307

             
                

               • G4 = 325

             

            Kaprio et al 2000 [232]

            To examine the contribution of genetic and other familial factors to the relationship between LTPA and CHD.

            • n = 8,205

            Length of Follow-up: 18 yrs

               • Number of Cases: 723

            LTPA compared to being sedentary helps prevent CHD in men.

              

            • Sex: Men

               
              

            • Age: 25-69 yr

             

            Multivariate RR (95% CI)

             

            Finland

             

            • Characteristics: Same sex twin pairs, free of CVD

            PA assessment: Questionnaire for LTPA, 3 groups:

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.84 (0.70-1.01)

             

            Prospective cohort

               

               • G3 = 0.68 (0.50-0.92)

             
               

            G1 = Sedentary

            p = 0.010

             
               

            G2 = Occasional

              

            D & B score = 12

              

            Exercisers

              
               

            G3 = Conditioning

              
               

            Exercisers

              
               

            Outcome Measure: Hospitalization or death from CHD

              
               

            Poisson regression

              

            Lakka et al 1994 [233]

            To investigate the independent associations of LTPA and maximal oxygen uptake with the risk of acute MI.

            • n = 1,166

            Baseline examination: 1984-1989

             

            Conditioning LTPA and VO2 max had an inverse, graded and independent association with the risk

              

            • Sex: Men

               
              

            • Age: 42-61 yr

             

            Adjusted RH (95% CI) by conditioning PA level

             

            Finland

             

            • Characteristics: Healthy with normal ECG

            PA assessment: Questionnaire for conditioning PA (h/wk), 3 groups (h/wk)

              
               

            G1 = <0.7

               • G1 = 1.00 (referent)

             

            Prospective cohort

              

            G2 = 0.7

               • G2 = 1.11 (0.58-2.12)

             
              

            • Kuopio Ischaemic Heart Disease Risk Factor Study

            G3 = >2.2

               • G3 = 0.31(0.12-0.85)

             

            D & B score = 13

               

            Adjusted RG (95% CI) by VO2 max

             
                

               • G1 = 1.00

             
               

            PF assessment: VO2 max (ml/kg/min)

               • G2 = 0.76 (0.38-1.50)

             
                

               • G3 = 0.26 (0.10-0.68)

             
               

            G1 = <28.0

              
               

            G2 = 28.0-33.6

              
               

            G3 = >33.6

              
               

            Outcome event: acute MI

              
               

            Cox proportional HR

              

            Laukkanen at al 2004 [234]

            To determine whether VO2peak predicts CVD morbidity and mortality in a sample of men as related to conventional risk factors, medications or underlying chronic disease.

            • 1,294 healthy; 1,057 unhealthy

            PF Assessment: VO2 peak (ml/kg/min) measured by exercise test with an electrically braked cycle ergometer, divided into quartiles

               • Number of Cases: 204 CV deaths, 323 non-fatal coronary events

            Dose-response relationship between directly measured PF and CVD death among healthy men at baseline.

            Finland

             

            • Sex: Men

             

            Healthy men with low VO2 peak (lowest quartile) had an increased risk

             
              

            • Age: 42-60 yr

               

            Prospective cohort

             

            • Characteristics: Healthy and not healthy participants

               
               

            Q1 = <27.6

            Adjusted RR (95% CI) by PF quartile Fatal MI

             
               

            Q2 = 27.6-32.2

             

            Unfit men with unfavorable risk profiles are the risk group that would benefit the most from preventative measures.

            D & B score = 11

              

            Q3 = 32.3-37.1

               • 3.29 (0.86-12.90)

             
              

            • Kuopio Ischaemic Heart Disease Risk Factor Study

            Q4 = >37.2

              
                

            Non-Fatal MI

             
               

            Outcome Measure: Incidence of fatal and non fatal CVD during 13 year follow-up

               • 2.16 (1.12-4.18)

             
               

            Cox proportional HR

              

            Lee at al 2000 [235]

            To investigate whether different durations of exercise episode are associated with different risk of CHD.

            • n = 7,307

            Baseline survey in 1988

               • Number of Cases: 482

            Longer durations of PA bouts are not associated with decreased CHD risk compared with shorter bouts, once total EE is taken into account.

              

            • Sex: Men

               

            USA

             

            • Age: Mean 66.1 ± 7.5

            PA assessment: Survey for EE (kJ/wk), divided into 5 groups and episodes of PA (min), divided into 6 groups

            Multivariate adjusted RR (95% CI) by EE

             
                

               • G1 = 1.00 (referent)

             
              

            • Characteristics: Healthy

             

               • G2 = 0.80 (0.57-1.12)

             
                

               • G3 = 0.80 (0.55-1.16)

             

            Prospective cohort

             

            • Harvard Alumni Study

             

               • G4 = 0.74 (0.47-1.17)

             
                

               • G5 = 0.62 (0.41-0.94)

             

            D & B score = 12

              

            Energy expenditure (kJ/wk)

             

            As long as the total EE is similar, more frequent shorter bouts or longer less frequent bouts have an equivalent reduction in CHD risk.

               

            G1 = <4,200

            Multivariate adjusted RR (95% CI) by duration of PA episode

             
               

            G2 = 4,200-8,399

              
               

            G3 = 8,400-12,599

              
               

            G4 = 12,600-16,799

               • G1 = 1.00 (referent)

             
               

            G5 = ≥ 16,800

               • G2 = 1.15 (0.70-1.87)

             
                

               • G3 = 1.01 (0.68-1.51)

             
                

               • G4 = 1.11 (0.67-1.84)

             
               

            Duration of PA episode (min)

               • G5 = 1.18 (0.77-1.80)

             
               

            G1 = None

               • G6 = 1.25 (0.83-1.87)

             
               

            G2 = 1-15

              
               

            G3 = 16-30

              
               

            G4 = 31-45

              
               

            G5 = 46-60

              
               

            G6 = >60

              
               

            Outcome Measure: Fatal and Non Fatal CHD

              
               

            Proportional hazards regression

              

            Lee et al 2003 [236]

            To investigate whether moderate- intensity exercise is associated with reduced CHD.

            • n = 7,337

            PA assessment: Survey rating usual level of exertion when exercising, divided into tertiles

               • Number of Cases: 551

            Inverse association between relative intensity of PA and the risk of CHD.

            USA

             

            • Sex: Male

             

            Multivariate adjustment RR (95% CI)

             
              

            • Age: Mean 66.1 yr

             

               • T1 = 1.00 (referent)

             
                

               • T2 = 0.87 (0.70-1.09)

             
              

            • Characteristics: Healthy

             

               • T3 = 0.92 (0.75-1.14)

             

            Prospective cohort

              

            Energy expenditure (kcal/wk)

              
              

            Harvard Alumni Study

               
               

            T1 = <1000

              

            D & B score = 13

              

            T2 = 1000-2499

              
               

            T3 = ≥ 2500

              
               

            Cox proportional HR

              

            Lemaitre et al 1999 [237]

            To investigate whether regular participation in moderate intensity activity confers overall protection from sudden primary cardiac arrest.

            • n = 355 cases, 503 controls

            PA assessment: Interview (with spouses) for LTPA, 7 groups

               • 355 cases

            Participation in moderate intensity LTPA was associated with a decreased risk of primary cardiac arrest.

              

            • Sex: Men and women

             

            RR (95% CI)

             

            USA

              

            G1 = No activity

               • G1 = 1.00 (referent)

             
              

            • Age: 25-74 yr

            G2 = Gardening only≤ 60 min/wk

               • G2 = 0.52 (0.21-1.28)

             

            Case control

             

            • Characteristics: Previously healthy prior to primary cardiac arrest. Control Subjects: Individually matched to case patients on age (within 7 years) and sex at a ratio of about 2:1 were randomly selected from community by random-digit dialing

            G3 = Gardening only > 60 min/wk

               • G3 = 0.34 (0.13 0.89)

             
               

            G4 = Walking ≤ 60 min/wk

               • G4 = 0.45 (0.17-1.19)

             

            D & B score = 11

              

            G5 = Walking > 60 min/wk

               • G5 = 0.27 (0.11-0.67)

             
               

            G6 = Moderate intensity

               • G6 = 0.31 (0.13-0.74)

             
               

            LTPA (not walking or gardening)

            G7 = 0.34 (0.16-0.75)

             
               

            G7 = High intensity LTPA

              
               

            Logistic regression analysis

              

            Lemaitre et al 1995 [238]

            To examine whether LTPA decreases the risk of MI in postmenopausal women.

            • n = 1,193

            PA assessment: Phone interview for LTPA, divided into quartiles of EE (mean kcal/wk)

               • Number of Cases: 268

            Risk of MI among postmenopausal women is decreased by 50% with modest LT energy expenditures, equivalent to 30-45 min of walking for exercise three times per week

              

            • Sex: Women

               
              

            • Age: Mean 67 yr

             

            Multivariate RR (95% CI)

             

            USA

               

               • Q1 = 1.00 (referent)

             
              

            • Characteristics: Postmenopaus al Cases: Diagnosed with non-fatal MI Controls: free from MI

            Q1 = 71

               • Q2 = 0.52 (0.34-0.80)

             

            Case control

              

            Q2 = 472

               • Q3 = 0.40 (0.26-0.63)

             
               

            Q3 = 1183

               • Q4 = 0.40 (0.25-0.63)

             

            D & B score = 11

              

            Q4 = 3576

            p = <0.001

             
               

            Outcome Measure: Diagnosed with non-fatal MI

              
               

            Logistic regression analysis

              

            Li et al 2006 [239]

            To examine independent and joint associations of PA and adiposity with CHD incidence.

            • n = 88,393

            Length of Follow-up: 20 yrs

               • Number of Cases: 2,358

            Physical inactivity independently contributes to the development of CHD in women.

              

            • Sex: Women

             

               • Number of Dropouts: <2% lost to follow-contributes to the development of CHD in women.

             

            USA

             

            • Age: 34-59 yr

             

            up

             
              

            • Characteristics: Nurses

            PA assessment: Questionnaire for LTPA (hr/wk), 3 groups

              

            Prospective cohort

               

            Multivariate HR (95% CI)

             
              

            • Nurses' Health Study

             

               • G1 = 1.00 (referent)

             
               

            G1 = ≥3.5

               • G2 = 1.34 (1.18-1.51)

             

            D & B score = 12

              

            G2 = 1-3.49

               • G3 = 1.43 (1.26-1.63)

             
               

            G3 = <1

              
               

            Outcome Measure: CHD incidence

              
               

            Cox proportional HR

              

            Lemaitre et al 1995 [240]

            To evaluate the effect of PA on MI occurrence.

            • n = 1,107 (726 controls, 381 cases)

            PA assessment: Questionnaire, 3-5 groups depending on variable

            OR (95% CI),

            PA level was inversely associated with occurrence of MI in both sexes, although the association presented a significant linear trend only for women; in men it suggested a u-shaped relation.

                

            Total PA, men

             

            Portugal

             

            • Sex: Men and women

             

               • G1 = 1.00 (referent)

             
               

            Total PA (MET hr/day), men

               • G2 = 0.54 (0.33-0.88)

             

            Case control

             

            • Age: ≥ 40 yr

             

               • G3 = 0.34 (0.20-0.59)

             
              

            • Characteristics: Case: Admitted to Hospital and diagnosed with first episode of MI Control: Healthy, no history of CHD

            G1 = 28.3-32.1

               • G4 = 0.59 (0.36-0.98)

             

            D & B score = 12

              

            G2 = 32.2-33.3

               • G5 = 0.90 (0.56-1.45)

             
               

            G3 = 33.4-36.5

            Trend p = 0.827

             
               

            G4 = 36.6-40.3

            Total PA, women

             
               

            G5 = 40.4-83.1

               • Q1 = 1.00 (referent)

             
               

            Total PA (MET hr/day), women

               • Q2 = 0.39 (0.21-0.73)

             
               

            Q1 = 28.9-32.7

               • Q3 = 0.33 (0.17-0.64)

             
               

            Q2 = 32.8-34.1

               • Q4 = 0.22 (0.11-0.47)

             
               

            Q3 = 34.2-37.8

            p = <0.001

             
               

            Q4 = 37.8-70.6

              
                

            Sport participation, men

             
               

            Sport participation (MET hr/day), men

               • G1 = 1.00 (referent)

             
               

            G1 = 0.0

               • G2 = 0.36 (0.19-0.69),

             
               

            G2 = 0.1-1.0

               • G3 = 0.72 (0.41-1.26),

             
               

            G3 = 1.1-2.0

               • G4 = 0.42 (0.23-0.76),

             
               

            G4 = 2.1-3.6

               • G5 = 0.31 (0.16-0.62)

             
               

            G5 = 3.7-15.4

            p = <0.001

             

            Lovasi et al 2007 [241]

            To investigate the shape of the relationship between LTPA and MI risk.

            • n = 4,094

            PA assessment: Telephone interview (Minnesota LTPA Questionnaire)

               • Number of Cases: 697

            Time engaged in LTPA, even non strenuous LTPA was associated with a lower risk of MI, and the shape of this relationship was non- linear

              

            • Sex: Men and women

             

            Adjusted OR (95% CI)

             

            USA

             

            • Age: 64 ± 9 yr

             

            LTPA and non fatal CHD

             
              

            • Characteristics: Group Health Cooperative Members

             

               • G1 = 1.00 (referent)

             

            Case control

              

            LTPA

               • G2 = 0.88 (0.66-1.17)

             
               

            G1 = None

               • G3 = 0.62 (0.46-0.83)

             

            D & B score = 11

              

            G2 = <2

               • G4 = 0.61 (0.45-0.82)

             
               

            G3 = 2-5

               • G5 = 0.59 (0.44-0.80)

             
               

            G4 = 5-9

              
               

            G5 = >9 h/wk

            Adjusted RR (95% CI) Strenuous LTPA and non Fatal CHD

             
               

            Strenuous LTPA

               • G1 = 1.00 (referent)

             
               

            G1 = None

               • G2 = 0.76 (0.59-0.99)

             
               

            G2 = non strenuous LTPA

               • G3 = 0.53 (0.40-0.70)

             
               

            G3 = Any Strenuous

              
               

            LTPA

              
               

            Outcome measure: non fatal CHD

              
               

            Logistic regression

              

            Manson et al 1999 [242]

            To assess the comparative roles of walking and vigorous exercise in the prevention of coronary events in women.

            • n = 72,488

            PA assessment:

               • Number of Cases: 645 coronary events

            Both walking and VPA are associated with a substantial reductions in incidence of CHD. Risk reductions for each were similar hen total PAy was similar. Walking 3 or more hours per week could reduce the risk of CHD by 30-40%.

              

            • Sex: Women

            Questionnaire with detailed information on PA.

              
              

            • Age: 40-65 yr

             

            Multivariate RR (95% CI) by total PA score

             

            USA

             

            • Characteristics: Healthy, no Previous history of CHD

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.88 (0.71-1.10)

             

            Prospective cohort

              

            Total PA score

               • G3 = 0.81(0.64-1.02)

             
               

            G1 = 1-2.0

               • G4 = 0.74 (0.58-0.95)

             
              

            Nurses' Health Study

            G2 = 2.1-4.6

               • G5 = 0.66 (0.51-0.86)

             

            D & B score = 12

              

            G3 = 4.7-10.4

            p = 0.002

             
               

            G4 = 10.5-21.7

              
               

            G5 = >21.7

              
                

            Multivariate RR (95% CI) by walking activity

             
                

               • G1 = 1.00 (referent)

             
               

            Walking, in those who did not participate in VPA: (MET hr/wk)

               • G2 = 0.78 (0.57-1.06)

             
               

            G1 = 0.5

               • G3 = 0.88 (0.65-1.21)

             
               

            G2 = 0.6-2.0

               • G4 = 0.70 (0.51-0.95)

             
               

            G3 = 2.1-3.8

               • G5 = 0.65 (0.47-0.91)

             
               

            G4 = 3.9-9.9

            p = 0.02

             
               

            G5 = ≥ 10

              
                

            Multivariate RR (95% CI) by walking pace

             
                

               • 1.00 (referent)

             
               

            Walking pace (mph)

               • 0.75 (0.59-0.96)

             
               

            G1 = <2.0

               • 0.64 (0.47-0.88)

             
               

            G2 = 2.0-2.9

              
               

            G3 = ≥ 3.0

              

            Mora et al 2007 [243]

            To investigate whether differences in several CV risk factors mediate the effect of PA on reduced risk of CVD.

            • n = 27,055

            10.9 ± 1.6 yr of follow up

               • Number of Cases: 640

            There remained a borderline significant inverse association between PA and risk of CHD after adjustment for all sets of risk factors.

              

            • Sex: Women

               
              

            • Age: ≥ 45 yr

            PA assessment: Questionnaires at study entry for categories of EE from PA (kcal/wk), 4 groups

            HR (95% CI), basic model

             

            USA

             

            • Characteristics: Healthy

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.84 (0.67-1.06)

             

            Prospective cohort

             

            • Women's health study

             

               • G3 = 0.76 (0.61-0.96)

             
                

               • G4 = 0.62 (0.48-0.82)

             
               

            G1 = <200

            p = 0.001

             

            D & B score = 13

              

            G2 = 200-599

             

            While all sets of risk factors should some mediation on the effect of PA on CHD none made the relationship insignificant

               

            G3 = 600-1499

            Multivariate adjusted HR (95% CI)

             
               

            G4 = ≥ 1500

               • G1 = 1.00 (referent)

             
                

               • G2= 0.71 (0.58-0.87)

             
               

            Outcome measure:

               • G3 = 0.64 (0.52-0.78)

             
               

            Incidence of CVD and

               • G4 = 0.48 (0.38-0.62)

             
                

            p = <0.001

             
               

            Cox proportional HR

              

            O'Connor et al 1995 [244]

            To examine the association between intensity of exercise and CHD risk.

            • n = 680 (532 men and 148 women)

            PA assessment: Home interview for PA, divided into quartiles

               • Number of Cases: 340

            Significant inverse association between PA level and the risk of non fatal MI in men, which persisted after adjustment for other risk factors.

                

            Adjusted OR (95% CI) by PA level, men

             
                

               • Q1 = 1.00 (referent)

             

            USA

             

            • Sex: Men and women

            Q1 = Lowest

               • Q2 = 0.60 (0.32-1.13)

             
               

            Q2

               • Q3 = 0.41 (0.21-0.78)

             

            Case control

             

            • Age: < 76 yr

            Q3

               • Q4 = 0.41 (0.22-0.77)

             
              

            • Characteristics: Cases: Diagnosed MI (non-fatal), no previous history of CHD. Controls: no history of CHD.

            Q4 = Highest

            p = 0.003

             

            D & B score = 12

              

            Outcome Measure: non-fatal MI

            Adjusted OR (95% CI) by PA level, women

             
                

               • Q1 = 1.00 (referent)

             
               

            Moderate- vigorous sports men Cut-points kcal/wk

               • Q2 = 1.07 (0.27-4.17)

             
               

            Q1 = Lowest

               • Q3 = 2.02 (0.56-7.38)

             
               

            Q2

               • Q4 = 1.29 (0.31-5.35)

             
               

            Q3

            p = 0.51

             
               

            Q4 = Highest

              
                

            Adjusted OR (95% CI) by moderate-vigorous sports, men

             
                

               • Q1 = 1.00 (referent)

             
               

            Moderate- vigorous sports Women

               • Q2 = 1.12 (0.60-2.10)

             
               

            Cut-points kcal/wk

               • Q3 = 0.61 (0.30-1.24)

             
               

            Q1 = Lowest

               • Q4 = 0.43 (0.20-0.92)

             
               

            Q2

            p = 0.02

             
               

            Q3

              
               

            Q4 = Highest

            Adjusted OR (95% CI) by moderate-vigorous sports, women

             
               

            Logistic regression analysis

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.31 (0.37-4.66)

             
                

               • Q3 = 1.90 (0.44-8.28)

             
                

               • Q4 = 0.35 (0.07-1.84)

             
                

            p = 0.62

             

            Rastogi et al 2004 [245]

            To examine the relation between PA and CHD risk in India.

            • n = 1,050

            PA assessment: Questionnaire

            Number of Cases: 350

            Observed a strong and dose dependent inverse association between LTPA and non fatal CHD.

              

            • Sex: Men and women

             

            Multivariate OR (95% CI) by LTPA

             

            USA

             

            • Age: 21-74 yr

            LTPA (MET min/d)

               • G1 = 1.00 (referent)

             
              

            • Characteristics: Cases: Diagnosed with MI (non fatal) Controls: non- cardiac patients

            G1 = 0

               • G2 = 0.96 (0.59-1.55)

             

            Case control

              

            G2 = 0-145

               • G3 = 0.44 (0.27-0.71)

             

            D & B score = 12

              

            G3 = ≥145

            p = 0.001

             
               

            Sedentary time (min/d)

            Multivariate OR (95% CI) by sedentary time

             
               

            G1 = <70

               • G1 = 1.00 (referent)

             
               

            G2 = 70-130

               • G2 = 1.15 (0.68-1.95)

             
               

            G3 = 130-215

               • G3 = 1.04 (0.61-1.76)

             
               

            G4 = ≥215

               • G4 = 1.88 (1.09-3.21)

             
                

            p = 0.02

             
               

            Outcome Measure: Non-fatal MI

              
               

            Conditional logistic regression

              

            Rodriguez et al 1994 [246]

            To examine the relationship between PA and 23 yr incidence of CHD morbidity and mortality.

            • n = 7,074

            23 year follow-up

               • Number of Cases: 789

            PA was associated with a significant reduction in the risk of CHD morbidity and mortality.

              

            • Sex: Men

               
              

            • Age: 45-64 yr

            PA assessment: Questionnaire for PA index, divided into tertiles

            Age adjusted RR (95% CI), CHD incidence

             

            USA

             

            • Characteristics: Japanese- American living in Oahu, Hawaii in 1965, < 65 years to reduce effect of retirement on PA levels

             

               • T1 = 1.00 (referent)

             
                

               • T2 = 1.01 (.86-1.19)

             

            Prospective cohort

              

            T1 = Low

               • T3 = 0.83 (0.86-1.19)

            These data support the hypothesis that PA is associated with a favorable profile of CVD risk factors.

               

            T2 = Moderate

              
               

            T3 = High

            Multivariate adjusted RR (95% CI), CHD incidence

             

            D & B score = 11

              

            Cox proportional regression model

               • T1 = 1.00 (referent)

             
                

               • T2 = 1.07 (0.90-1.26)

            This study did not show a dose- response relationship since the medium tertile of PA showed increased rates of CHD compared to the inactive group.

              

            • The Honolulu Heart Program

             

               • T3 = 0.95 (0.80-1.14)

             
                

            Age adjusted RR (95% CI), CHD mortality

             
                

               • T1 = 1.00 (referent)

             
                

               • T2 = 1.12 (0.88-1.44)

             
                

               • T3 = 0.74 (0.56-0.97)

             
                

            Multivariate adjusted RR (95% CI)

             
                

               • T1 = 1.00 (referent)

             
                

               • T2 = 1.19 (0.93-1.53)

             
                

               • T3 = 0.85 (0.65-1.13)

             

            Rothenbacher et al 2003 [247]

            To estimate the risk for CHD associated with LTPA.

            • n = 791 (312 cases; 479 controls)

            PA assessment: Interview

            Number of Cases: 312

            LTPA showed a clear inverse association with risk of CHD.

               

            LTPA (h/wk)

            Multivariate OR (95% CI), LTPA

             

            Germany

             

            • Sex: Men and Women

            G1 = 0

            Winter

             
               

            G2 = <1

               • G1 = 1.00 (referent)

             

            Case control

             

            Age: 40-68 yr

            G3 = 1-2

               • G2 = 0.48 (0.27-0.84)

             
              

            Characteristics: Cases: stable CHD diagnosed within 2 years, no recent MI, Controls: no history of CHD.

            G4 = >2

               • G3 = 0.54 (0.369-0.82)

             

            D & B score = 12

               

               • G4 = 0.27 (0.19-0.47)

             
               

            Workday activity by

              
               

            bike/foot, (min/workday)

            Summer

             
               

            G1 = <15

               • G1 = 1.00 (referent)

             
               

            G2 = 15-30

               • G2 = 0.85 (0.47-1.53)

             
               

            G3 = 30-60

               • G3 = 0.60 (0.38-0.95)

             
               

            G4 = >60

               • G4 = 0.39 (0.26-0.59)

             
               

            Outcome Measure: non fatal CHD

            Multivariate OR (95% CI), workday activity by bike/foot

             
               

            Unconditional logistic regression, linear regression model

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.53 (0.30-0.93)

             
                

               • G3 = 0.36 (0.21-0.62)

             
                

               • G4 = 0.58 (0.36-0.94)

             

            Seccareccia and Menotti 1992 [248]

            To examine the relationship between OPA and the risk of CHD death.

            • n = 1,621

            25 year of follow-up

            • 189 cases

            Increase in OPA is inversely related to risk of CHD death.

              

            • Sex: Men

               
              

            • Age: 40-59 yr

            PA assessment: Questionnaire for OPA (kcal/d), 3 groups

            Age Standardized CHD and deaths rates:

             
              

            • Characteristics: Healthy

             

               • G1 = 18.9 ± 3.1

             

            Italy

               

               • G2 = 13.1 ± 1.7

             
               

            G1 = Sedentary, < 2400

               • G3 = 11.0 ± 0.9

             

            Prospective cohort

              

            G2 = Moderate, 2400-3199

              

            D & B score = 11

              

            G3 = Heavy ≥ 3200

              
               

            Indicators of PF including HR, vital capacity, FEV in 3/4 of sec, and corrected arm circumference (minus contribution of fat).

              
               

            End Point: Fatal CHD

              

            Sesso et al 2000 [249]

            To examine the association of the quantity and intensity of PA with CHD risk and the impact of other coronary risk factors.

            • n = 12,516

            PA assessment: Questionnaire

            Number of Cases: 2,135

            L-Shaped association between PA and the risk of CHD, with a reduction in CHD risk of approximately 20% for total PA levels >4200 kJ/wk

              

            • Sex: Men

               
              

            • Age: 39-88 yr

             

            Multivariate HR (95% CI)

             

            USA

             

            • Characteristics: Healthy

            PA Index (kJ/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = <2100

               • G2 = 0.90 (0.79-1.03)

             

            Prospective cohort

             

            • Harvard Alumni

            G2 = 2100-4199

               • G3 = 0.81 (0.71-0.92)

             
              

            Study

            G3 = 4200-8399

               • G4 = 0.80 (0.69-0.93)

             
               

            G4 = 8400-12599

               • G5 = 0.81 (0.71-0.94)

             

            D & B score = 12

              

            G5 = >12600

            p = 0.003

            Suggests that vigorous activities are associated with a reduced risk of CHD, whereas moderate or light PA has no clear association with risk of CHD.

               

            Cox proportional HR

              

            Sundquist et al 2005 [250]

            To examine the long term effect of LTPA on incident cases of CHD.

            • n = 5,196 (2,645 men, 2,551 women)

            PA assessment: Questionnaire Levels of PA

            Age and sex adjusted RR (95% CI)

            Positive long term effect of LTPA on CHD risk among men and women.

                

               • Q1 = 1.00 (referent)

             

            Sweden

             

            • Sex: Men and women

            Q1 = None

               • Q2 = 0.72 (0.51-1.00)

             
               

            Q2 = Occasionally

               • Q3 = 0.64 (0.46-0.89)

             

            Prospective cohort

             

            Age: 35-74 yr

            Q3 = 1-2 times per week

               • Q4 = 0.46 (0.29-0.74)

             
              

            • Characteristics: Those not hospitalized for CHD in the last 2 years and those who rate their general health as poor were excluded

            Q4 = Vigorous ≥2 times per week

            Multivariate adjusted RR (95% CI)

             

            D & B score = 11

              

            Outcome Measure: Fatal or non fatal CHD

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.76 (0.55-1.07)

             
                

               • Q3 = 0.74 (0.53-1.04)

             
                

               • Q4 = 0.59 (0.37-0.95)

             
               

            Cox regression model

              

            Talbot et al 2002 [251]

            To examine the contributions of LTPA and aerobic fitness to the risk of coronary events in healthy younger and older adults.

            • n = 689

            Surveys began in 1960 and were completed on every visit

               • Number of Cases: 63

            In younger men PF predicts a reduced risk of CHD but not LTPA.

              

            • Sex: Men

               
              

            • Age:

             

            After adjusting for coronary risk factors there was:

             

            USA

             

            51.6 ± 16.8 yr

               
              

            • Characteristics: Community dwelling

            PA assessment: Survey for LTPA (97 activities) at every visit.

            RR: 0.53 (p < 0.001) and

            In older men, high intensity LTPA and PF appear to be of similar importance in reducing CHD risk.

            Prospective cohort

               

            RR: 0.61 (p = 0.024) in older men.

             

            D & B score = 12

             

            • Baltimore Longitudinal Study of Aging

            PF assessment: Treadmill VO2 max test on alternate visits

            Total LTPA was unrelated to coronary risk in either age group.

             
                

            With 3 levels of LTPA intensity substituted for total LTPA:

             
               

            Unpaired t-tests and chi square tests. Cox Proportional hazards Analysis

            RR = 0.39 for tertile 3 vs. tertile 1

             

            Tanasescu et al 2002 [252]

            To assess the amount, type and intensity of PA in relation to risk of CHD in men.

            • n = 44,452

            PA assessment: Questionnaire

               • Number of Cases: 1,700

            Total PA, running, weight training, and walking were associated with a reduced risk for CVD.

              

            • Sex: Men

               
              

            • Age: 40-75 yr

             

            Age adjusted HR (95% CI) by total PA

             

            USA

             

            • Characteristics: Health professionals, no history of CHD and in good health

            Total PA (MET hr/wk)

               • Q1 = 1.00 (referent)

             
               

            Q1 = 0-6.32

               • Q2 = 0.85 (0.74 0.98)

             

            Prospective cohort

              

            Q2 = 6.33-14.49

               • Q3 = 0.78 (0.67-0.92)

             
               

            Q3 = 14.50-25.08

               • Q4 = 0.72 (0.62-0.83)

            The average exercise intensity was associated with a reduced risk (independent of total PA).

               

            Q4 = 25.09-41.98

               • Q5 = 0.58 (0.49-0.68)

             

            D & B score = 11

              

            Q5 = > 41.99

            p = .001

             
              

            • Health Professionals follow-up study

            Exercise intensity (METs)

            Age adjusted HR (95% CI) by exercise intensity

             
               

            G1 = Low-1-4

               • G1 = .00 (referent)

             
               

            G2 = Mod.-4-6

               • G2 = 0.94 (0.83-1.04)

             
               

            G3 = High 6-12

              
               

            Walking pace independent of total volume of PA (mph)

               • G3 = 0.83 (0.72-0.97)

             
                

            p = 0.02

             
               

            Q1 = <2

            Age adjusted HR (95% CI) by walking pace

             
               

            Q2 = 2-3

               • Q1 = 1.00 (referent)

             
               

            Q3 = 3-4

               • Q2 = 0.72 (0.54-0.94)

             
               

            Q4 = > 4

               • Q3 = 0.61 (0.45-0.81)

             
                

               • Q4 = 0.51 (0.31-0.84)

             
               

            Outcome Measure: Nonfatal MI or Fatal CHD occurring during follow-up

            p <0.001

             
               

            Cox proportional HR

              

            Vatten et al 2006 [253]

            To investigate whether obesity- related CV mortality could be modified by PA.

            • n = 54,284 (27,769 men; 26,515 women)

            Length of Follow-up: 16 years

               • Number of Cases: 2,462

            Increased PA reduces the risk of death in women, but not in men.

                

            Multivariate HR (95% CI), men

             

            Norway

             

            • Sex: Men and women

            PA assessment:

               • Q1 = 1.00 (referent)

             
               

            Questionnaire

               • Q2 = 1.01 (0.89-1.16)

             

            Prospective cohort

             

            Age: ≥ 20 yr

            Divided into 4 groups

               • Q3 = 0.98 (0.84-1.14)

             
              

            • Characteristics: Free from CVD at baseline

            Q1 = High

               • Q4 = 1.18 (1.00-1.38)

             
               

            Q2 = Medium

            p = 0.11

             

            D & B score = 12

              

            Q3 = Low

              
              

            • HUNT study

            Q4 = Never

            Multivariate HR (95% CI), women

             
               

            Outcome Measure: Ischemic heart disease mortality

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.23 (1.01-1.51)

             
                

               • Q3 = 1.54 (1.24-1.91)

             
                

               • Q4 = 1.52 (1.23-1.88)

             
               

            Cox proportional HR

            p <0.001

             

            Wagner et al 2002 [254]

            To investigate if the association between PA patterns and incidence of coronary events could explain the gradient in CHD observed between 2 countries.

            • n = 9,758

            Length of Follow-up: 5 yrs

            Number of Cases: 167 hard CHD, 154 angina events

            Beneficial effect of LTPA EE on hard CHD incidence in middle aged men.

              

            • Sex: Men and women

            PA assessment: Questionnaire for LTPA, 3 groups:

            Number of Dropouts: < 2%

             

            Ireland/France

             

            • Age: 50-59 yr

               
              

            • Characteristics: Healthy at Baseline

             

            HR (95% CI), hard events

             

            Prospective cohort

              

            G1 = Lowest

               • G1 = 1.00 (referent)

             
               

            G2 = Middle

               • G2 = 0.73 (0.51-1.05)

             
               

            G3 = Highest

               • G3 = 0.66 (0.46-0.96)

             

            D & B score = 12

              

            Outcome Measure: CHD hard events and Angina

            p = 0.04

             
                

            HR (95% CI), angina

             
                

               • G1 = 1.00 (referent)

             
               

            Cox proportional HR

               • G2 = 0.83 (0.55-1.25)

             
                

               • G3 = 1.28 (0.88-1.86)

             
                

            p = 0.10

             

            D & B score, Downs and Black quality score; YR, years; G, groups; CHD, coronary heart disease; RR, risk ratio; 95% CI, 95% confidence interval; PA, physical activity; VPA, vigorous physical activity; CV, cardio vascular; MET, metabolic equivalent; kcal/wk, kilocalories per week; Q, quartile or quintile; km/h, kilometers per hour; LTPA, leisure-time physical activity; HR, hazard ratio; OPA, occupational physical activity; kcal/kg/day kilocalories per kilogram per day; MI, myocardial infarction; ECG, electrocardiogram; kcal/kg/h kilocalories per kilogram per hour; mph, miles per hour; CVD, cardiovascular disease.

            Similar to the all-cause mortality data, the risk for cardiovascular disease demonstrates a graded inverse dose-response relationship to physical activity and fitness. The relative reduction in the incidence of cardiovascular disease averages 33% (median risk reduction of 36%), with greater risk reductions in studies that employed objective measures of aerobic fitness. It is not uncommon for studies to demonstrate a 50% or higher risk reduction when an objective measure of physical fitness was taken (Table 12). The importance of physical activity may actually be underestimated owing to multivariate control for many confounding factors (as discussed previously) and the fact that effects of within-person variation in physical activity are often not considered [55]. The relative risk reduction appears to be similar for men and women, and also appear to extend to non-Caucasian populations [56]. Some evidence also exists indicating that small amounts of physical activity are associated with lower cardiovascular-disease related mortality [57, 58]. Similar to all-cause mortality, physical activity confers health benefits independent of other known risk factors [42, 59]. Collectively, the level of evidence would be considered to be Level 2A based on the presence of overwhelming evidence from observational trials. The quality of the investigations was generally high with a mean (and median) Downs and Black score of 12 (range 9-14).

            Implications

            Research in the field began with the landmark work of Morris and colleagues, which demonstrated that men in physically demanding occupations (bus conductors and postmen) had a significantly lower risk of heart disease than individuals who worked in less demanding jobs (bus drivers and office workers) [45]. Since then considerable research has examined the relationship between physical activity and the risk for cardiovascular disease. In fact, several systematic reviews of the literature have been developed regarding the role of habitual physical activity in the primary and secondary prevention of cardiovascular disease [33, 6062]. The research to date has been consistent and compelling, habitual physical activity reduces markedly the risk for cardiovascular disease.

            Based on the available literature, there is compelling evidence that the recommendation of 30 min of moderate intensity exercise on most days of the week (equivalent to 4.2 MJ/wk or 1000 kcal/wk) reaches a threshold associated with significant reductions in cardiovascular-related mortality [32, 63]. Brisk walking has also been shown to be preferable to a slower pace [64]. However, weekly exercise volumes of less than 4.2 MJ (1000 kcal) may be cardio-protective [14, 59, 6567]. For instance, Lee et al. (2001) found that as little as 1 hr/wk of walking was associated with a 50% lower cardiovascular disease mortality in one sample of women. Wisloff et al. [58] reported that a single weekly bout of self-reported high intensity exercise was associated with a lower risk of cardiovascular death relative to those reporting no activity in both men (RR = 0.61, 95% CI = 0.49-0.75), and women (RR = 0.49, 95% CI = 0.27-0.89). Moreover, no additional benefit was seen with higher durations or frequency of exercise sessions [58]. The authors stated that this evidence challenges "current recommendations that require at least 1000 kcal of caloric expenditure per week to achieve exercise-induced protection against premature cardiovascular death." However, this research is in fact supportive of the Canadian guidelines which recognize the potential health benefits of low volumes of physical activity as reflected by the statement "Every little bit counts, but more is even better - everyone can do it!" It however should be noted that the statement "more is even better" is supported by a strong evidence base.

            Recommendation #2

            For a reduced risk for cardiovascular disease-related events and mortality, it is recommended that individuals participate in 30 min or more of moderate to vigorous exercise on most days of the week. Greater health benefits appear to occur with high volume and/or intensities of activity. Health benefits may also occur with as little as one hr of brisk walking per week. [Level 2, Grade A]

            The Primary Prevention of Stroke

            Stroke affects a significant proportion of Canadian society with approximately 50,000 new cases each year [68]. The relationship between physical activity and the risk for stroke is compelling, supporting at least a 25-30% risk reduction in the most active individuals [31]. In fact, in a review of the literature Katzmarzyk and Janssen [20] reported that lack of physical activity carried a relative risk of 1.60 (95% CI = 1.42-1.80) for stroke, similar to or higher than that for coronary heart disease (1.45), hypertension (1.30), colon cancer (1.41), breast cancer (1.31), type 2 diabetes (1.50), and osteoporosis (1.59).

            In our systematic review of the literature, a total of 1104 citations were identified during the electronic database search (Figure 5). Of these citations, 405 were identified in MEDLINE, 183 in EMBASE, 227 in Cochrane, and 289 in the CINAHL/SportDiscus/PsychInfo search. A total of 13 duplicates were found, leaving a total of 1091 unique citations. A total of 1011 articles were excluded after scanning, leaving a total of 80 articles for full review. An additional 9 articles were retrieved through cross-referencing and the authors' knowledge of the field. From these articles 64 were excluded after full review leaving 25 articles for inclusion in the systematic review. The reasons for exclusion included non-experimental/weak design (poor execution introducing bias) (n = 16), did not contain three levels of physical activity or not possible to determine dose-response relationship (n = 14), reviews, summaries, meta-analyses (n = 17), dissertations, thesis, abstracts (n = 8), and other (n = 9). Therefore, a total of 25 articles were included in the systematic review of the literature regarding the relationship between physical activity and the primary prevention of stroke (Table 13).
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig5_HTML.jpg
            Figure 5

            Results of the Literature Search for Stroke.

            Table 13

            Studies examining the relationship between physical activity and stroke.

            Publication Country Study Design Quality Score

            Objective

            Population

            Methods

            Outcome

            Comments and Conclusions

            Wisloff et al 2006 [58]

            To assess exercise amount and intensity in relation to subsequent CVD mortality (including stroke).

            • n = 27,143 men, 28,929 women

            16 year follow up

            Multivariate adjusted RR (95% CI) Men

            Both high and low- intensity exercise may be associated with a reduced risk of stroke in both men and women.

            Norway

             

            • Sex: Men and women

            PA Assessment: Questionnaire

            G1 = 1.00 (referent)

             
              

            • Age: ≥ 20 yr

             

            G2 = 0.90 (0.70-1.17)

             
              

            • Characteristics: free from CVD

            PA

            G3a = 0.90 (0.64-1.26)

             
              

            • HUNT Study

            G1 = None

            G3b = 0.59 (0.27-1.27)

             
               

            G2 = <1/wk

            G3c = 0.62 (0.40-0.95)

             
               

            G3a = 1/wk ≤ 30 min low

            G3d = 0.51 (0.31-0.86)

             
               

            G3b = 1/wk ≤ 30 min high

            G4a = 0.72 (0.49-1.05)

             
               

            G3c = 1/wk > 30 min low

            G4b = 0.63 (0.31-1.30)

             

            Prospective cohort

              

            G3d = 1/wk > 30 min high

            G4c = 1.02 (0.72-1.44)

             
               

            G4a = 2-3/wk ≤ 30 min low

            G4d = 0.59 (0.37-0.92)

             
               

            G4b = 2-3/wk ≤ 30 min high

            G5a = 0.97 (0.70-1.36)

             

            D & B score = 12

              

            G4c = 2-3/wk > 30 min low

            G5b = 0.68 (0.27-1.66)

             
               

            G4d = 2-3/wk > 30 min high

            G5c = 0.81 (0.65-1.20)

             
               

            G5a = ≥ 4/wk ≤ 30 min low

            G5d = 0.67 (0.49-1.11)

             
               

            G5b = ≥ 4/wk ≤ 30 min high

              
               

            G5c = ≥ 4wk > 30 min low

            RR (95% CI) Women

             
               

            G5d = ≥ 4/wk > 30 min high

            G1 = 1.00 (referent)

             
               

            Outcome Measure: IHD mortality

            G2 = 1.01 (0.81-1.25)

             
               

            Cox proportional HR

            G3a = 0.88 (0.68-1.15)

             
                

            G3b = 0.98 (0.46-2.10)

             
                

            G3c = 0.63 (0.42-0.94)

             
                

            G3d = 1.00 (0.50-1.98)

             
                

            G4a = 0.91 (0.70-1.17)

             
                

            G4b = 1.44 (0.78-2.65)

             
                

            G4c = 0.62 (0.44-0.88)

             
                

            G4d = 0.77 (0.36-1.66)

             
                

            G5a = 0.74 (0.56-0.99)

             
                

            G5b = 0.40 (0.10-1.62)

             
                

            G5c = 0.63 (0.45-0.89)

             
                

            G5d = 0.51 (0.21-1.26)

             

            Abbott et al 2003 [69]

            To examine the way in which risk factor effects on the incidence of thromboembolic and hemorrhagic stroke can change over a broad range of ages.

            • n = 7,589

            6, 15 and 26 year follow up

            Incidence rates per 1000 of stroke:

            The protective effect of PA on reducing risk of stroke increased with age.

            USA

             

            • Sex: Men

             

               • G1 = 9.0 (49)

             
              

            • Age: 45-93 yr

            PA assessment: Using PA index over a 24 hour period PA information collected at study enrolment 1965-1968 and updated at physical examinations that occurred at 6, 15 and 26 years into follow-up.

               • G2 = 17.8 (124)

             

            Prospective cohort

             

            • Characteristics: Free from CHD and stroke at enrolment; Japanese ancestry living on the island of Oahu, Hawaii.

            Grouped into 4 age groups, yr:

               • G3 = 33.4 (112)

             

            D & B score = 14

             

            • Honolulu Heart Program

            G1 = 45-54

               • G4 = 48.1 (111)

             
               

            G2 = 55-64

            Incidence of stroke event increased with advancing age p <0.001

             
               

            G3 = 65-74

            There appeared to be a small protective effect within each age group. Inverse relations increased with age (p = 0.046). The protective effect of PA became significant in men >77 years (p = 0.032)

             
               

            G4 = 75-93

              
               

            Outcome Measure: diagnosis of fatal and non fatal stroke during 26 years of follow-up

              
               

            Cox proportional HR

              

            Gillium et al 1996 [70]

            To examine the relationship between recreational and non-recreational PA and risk of stroke.

            • n = 2,368 men, 2,713 women

            11.6 year follow up

            Number of Cases: 249 white women, 270 white men, 104 black

            Sedentary behaviour was found to be associated with increased risk of stroke.

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire divided into tertiles:

              
              

            • Age: 45-74 yr

            T1 = Low

            RR (95% CI) Black men and women Recreational PA

             

            Prospective cohort

             

            • Ethnicity: Black and white

            T2 = Medium

               • T1 = 1.33 (0.67-2.63)

             

            D & B score = 12

             

            • NHANES I

            T3 = High

               • T2 = 1.33 (0.63-2.79)

             
                

               • T3 = 1.00 (referent)

             
               

            Outcome Measure: Total Stroke

            Non-recreational PA

             
               

            Cox proportional HR

               • T1 = 1.40 (0.90-2.16)

             
                

               • T2 = 1.41 (0.74-2.70)

             
                

               • T3 = 1.00 (referent)

             
                

            RR (95% CI) White men age 45-64 Recreational PA

             
                

               • T1 = 1.24 (0.63-2.41)

             
                

               • T2 = 1.17 (0.61-2.27

             
                

               • T3 = 1.00 (referent)

             
                

            Non-recreational PA

             
                

               • T1 = 1.07 (0.40-2.86)

             
                

               • T2 = 1.75 (1.04-2.96)

             
                

               • T3 = 1.00 (referent)

             
                

            RR (95% CI) White women age 45-64 Recreational PA

             
                

               • T1 = 3.13 (0.95-10.32)

             
                

               • T2 = 1.80 (0.52-6.22)

             
                

               • T3 = 1.00 (referent)

             
                

            Non-recreational PA

             
                

               • T1 = 3.51 (1.66-7.46)

             
                

               • T2 = 1.07 (0.57-1.99)

             
                

               • T3 = 1.00 (referent)

             
                

            RR (95% CI) White men age 65-74 Recreational PA

             
                

               • T1 = 1.29 (0.58-1.88)

             
                

               • T2 = 0.86 (0.58-1.28)

             
                

               • T3 = 1.00 (referent)

             
                

            Non-recreational

             
                

               • T1 = 1.82 (1.15-2.88)

             
                

               • T2 = 1.20 (0.88-1.64)

             
                

               • T3 = 1.00 (referent)

             
                

            RR (95% CI) White women age 65-75 Recreational PA

             
                

               • T1 = 1.55 (0.95-2.53)

             
                

               • T2 = 1.27 (0.76-2.12)

             
                

               • T3 = 1.00 (referent)

             
                

            Non-recreational PA

             
                

               • T1 = 1.82 (1.10-3.02)

             
                

               • T2 = 1.42 (1.01-2.00)

             
                

               • T3 = 1.00 (referent)

             

            Lee and Blair 2002 [71]

            To examine the association between PF and stroke mortality in men.

            • n = 16,878

            Baseline medical evaluation between 1971 and 1994 with average follow up period of 10 years

            Average estimated maximal METs

            Moderate and high levels of PF were associated with lower risk of stroke mortality in men.

              

            • Sex: Men

             

               • T1 = 8.5 MET

             
              

            • Age: 40-87 yrs

             

               • T2 = 10.5 MET

             

            USA

             

            • Aerobics Center Longitudinal Study

             

               • T3 = 13.1 MET

             

            Prospective cohort

              

            PF assessment: Maximal exercise tolerance test, divided into tertiles

            RR (95% CI) adjusted for age and exam year

             
                

               • T1 = 1.00 (referent)

             

            D & B score = 13

              

            T1 = Low

               • T2 = 0.35 (0.16-0.77)

             
               

            T2 = Moderate

               • T3 = 0.28 (0.11-0.71)

             
               

            T3 = High

            Trend p = 0.005

             
               

            Cox proportional HR

              

            Hu et al 2000 [72]

            To examine the association between PA and risk of total stroke and stroke sub- types in women.

            • n = 72,488

            Baseline measurement in 1986 with follow-up questionnaire in 1988 and 1992

            • 407 cases of stroke (258 ischemic strokes, 67 subarachnoid hemorrhages, 42 intracerebral hemorrhages, and 40 strokes of unknown type)

            PA, including moderate-intensity exercise such as walking, is associated with a substantial reduction in risk of total and ischemic stroke in a dose- response manner.

              

            • Sex: Women

               
              

            • Age:40-65 yr

               

            USA

             

            • Characteristics: Nurses

               

            Prospective cohort

             

            • Nurses' Health Study

            PA assessment: Questionnaire for total PA (MET h/wk), divided into quintiles, walking activity (MET h/wk), divided into quintiles and walking pace

            Multivariate RR (95% CI) for total stroke by total PA level

             
                

               • Q1 = 1.00 (referent)

             

            D & B score = 13

               

               • Q2 = 0.98

             
                

               • Q3 = 0.82

             
                

               • Q4 = 0.74

             
                

               • Q5 = 0.66

             
               

            Total PA (MET h/wk)

              
                

            p = 0.005

             
               

            Q1 = 0 - 2.0

              
               

            Q2 = 2.1 - 4.6

              
                

            Multivariate RR (95% CI) for ischemic Stroke by total PA level

             
               

            Q3 = 4.7 - 10.4

              
               

            Q4 = 10.5-21.7

              
                

               • Q1 = 1.00 (referent)

             
               

            Q5 = > 21.7

              
                

               • Q2 = 0.87

             
               

            Walking activity (MET h/wk)

               • Q3 = 0.83

             
               

            Q1 = 0.5

               • Q4 = 0.76

             
               

            Q2 = 0.6 - 2.0

               • Q5 = 0.52

             
               

            Q3 = 2.1 - 3.8

            p = 0.003

             
               

            Q4 = 3.9 - 10

              
               

            Q5 = 10

            Multivariate RR (95% CI) for total stroke by walking activity

             
               

            Walking pace (mph)

               • Q1 = 1.00 (referent)

             
               

            G1 < 2.0

               • Q2 = 0.76

             
               

            G2 = 2-2.9

               • Q3 = 0.78

             
               

            G3 3.0

               • Q4 = 0.70

             
                

               • Q5 = 0.66

             
               

            Outcome measure: Stroke incidence

            p = 0.01

             
                

            Multivariate RR (95% CI) for ischemic stroke by walking activity

             
               

            Pooled logistic regression

              
               

            Cox proportional HR

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.77

             
                

               • Q3 = 0.75

             
                

               • Q4 = 0.69

             
                

               • Q5 = 0.60

             
                

            p = 0.02

             
                

            Multivariate RR (95% CI) for total stroke by usual Walking Pace

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.81

             
                

               • G3 = 0.49

             
                

            p < 0.001

             
                

            Multivariate RR (95% CI) for ischemic stroke by usual walking pace

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.71

             
                

               • G3 = 0.47

             
                

            p < 0.001

             

            Lee et al 1999 [74]

            To examine the association between exercise and stroke risk.

            • n = 21,823

            11.1 year follow up

            Number of Cases: 533

            VPA is associated with a decreased risk of stroke in men.

              

            • Sex: Men

               
              

            • Age: 40-84 yr

            PA assessment: Questionnaire for frequency of VPA, divided into 4 groups

            Multivariate RR1 (95% CI) for total stroke by VPA

             

            USA

                 
                

               • G1 = 1.00 (referent)

             

            Prospective cohort

               

               • G2 = 0.79 (0.61-1.03)

            Inverse association with PA seemed to be mediated through beneficial effects on body weight, BP, cholesterol and glucose tolerance.

               

            G1 < 1 time/week

               • G3 = 0.80 (0.65-0.99)

             
               

            G2 = 1 time/week

               • G4 = 0.79 (0.61-1.03)

             

            D & B score = 13

              

            G3 = 2-4 times/week

            p = 0.04

             
               

            G4 ≥ 5 times/week

            RR2 (95% CI) for total stroke by VPA

             
                

               • G1 = 1.00 (referent)

             
               

            RR1 = adjusted for smoking, alcohol consumption, history of angina and parental history of MI at <60 years

               • G2 = 0.81 (0.61-1.07)

             
                

               • G3 = 0.88 (0.70-1.10)

             
                

               • G4 = 0.86 (0.65-1.13)

             
                

            p = 0.25

             
                

            RR2 (95% CI) for ischemic stroke by

             
               

            RR2 = adjusted for all of the above plus, BMI, history of, hypertension, high cholesterol and diabetes

              
                

            VPA

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.90 (0.66-1.22)

             
                

               • G3 = 0.95 (0.74-1.22)

             
                

               • G4 = 0.97 (0.71-1.32)

             
               

            Outcome Measure: Total Stroke (Ischemic and Hemorrhagic)

            p = 0.81

             
                

            RR2 (95% CI) for hemorrhagic stroke by VPA

             
               

            Cox proportional HR

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.54 (0.25-1.13)

             
                

               • G3 = 0.71 (0.41-1.23)

             
                

               • G4 = 0.54 (0.26-1.15)

             
                

            p = 0.10

             

            Bijnen et al 1998 [166]

            To describe the association between the PA patterns of elderly men and stroke mortality.

            • n = 802

            10 year follow up

            Number of Cases: 47

            No significant finding

              

            • Sex: Men

               
              

            • Age:64-84 yr

            PA assessment:

            Multivariate adjusted RR (95% CI)

             

            Denmark

             

            • Characteristics: Not all free from previous stroke

            Questionnaire for LTPA, divided into tertiles

               • T1= 1. 00 (referent)

             
                

               • T2 = 0.65 (0.33-1.25)

             

            Prospective cohort

              

            T1 = Lowest

               • T3 = 0.55 (0.24-1.26)

             
               

            T2

            p = 0.12

             
               

            T3 = Highest

              

            D & B score = 15

                 
               

            Outcome Measure: Stroke Mortality

              
               

            Cox proportional HR

              

            Schnohr et al 2006 [214]

            To describe the association between different levels of LTPA and subsequent causes of death (stroke).

            • n = 2136 men, 2,758 women

            5 year follow up

            RR (95% CI), univariate

            Although RR for of death from stroke was below 1 for both moderate and high compared with low PA, this association did not reach the level of statistical significance.

                

               • G1 = 1.00 (referent)

             
              

            • Sex: Men and women

            PA assessment:

               • G2 = 0.64 (0.39-1.05)

             

            Copenhagen

             

            • Age: 20 -- 79 yr

            Questionnaire for LTPA,

               • G3 = 0.70 (0.41-1.21)

             
              

            • Characteristics: Healthy, PA level did not change between 2 examinations, 5 years apart

            divided into 3 groups

            Trend p = 0.4

             

            Prospective cohort

              

            G1 = Low PA (<4 METS)

              
               

            G2 = Moderate PA (4-6

            RR (95% CI), multivariate:

             
               

            METS)

               • G1 = 1.00 (referent)

             

            D & B score = 13

              

            G3 = High PA (>6 METS)

               • G2 = 0.67 (0.40-1.12)

             
              

            • Copenhagen City Heart Study

             

               • G3 = 0.76 (0.43-1.34)

             
               

            Multivariate Analysis Kaplan-Meier Plots

            Trend p = 0.6

             
               

            Linear, Logistical and Cox Regression.

              

            Vatten et al 2006 [253]

            To investigate whether obesity- related CV mortality could be modified by PA.

            • n = 26,515 men, 27,769 women

            16 year follow up

            Number of Cases: 994 women, 771 men

            Lower levels of TPA are associated with an increased risk of stroke.

              

            • Sex: Men and women

            PA assessment: Questionnaire for total amount of PA, divided into 4 groups

              

            Norway

             

            • Age: 20 yr

             

            Multivariate HR (95% CI), men

             
              

            • Characteristics: Free from CVD at baseline

             

               • Q1 = 1.00 (referent)

             

            Prospective cohort

               

               • Q2 = 1.05 (0.85-1.30)

             
              

            • HUNT study

            G1 = High

               • Q3 = 1.21 (0.95-1.54)

             
               

            G2 = medium

               • Q4 = 1.35 (1.05-1.74)

             

            D & B score = 14

              

            G3 = low

            p = 0.009

             
               

            G4 = never

              
                

            Multivariate HR (95% CI), women

             
               

            Outcome Measure: Stroke mortality

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.16 (0.93-1.45)

             
                

               • Q3 = 1.45 (1.14-1.86)

             
               

            Cox proportional HR

              
                

               • Q4 = 1.45 (1.14-1.83)

             
                

            p < 0.001

             

            Agnarsson et al 1999 [255]

            To examine the association of LTPA and pulmonary function with the risk of stroke.

            • n = 4,484

            Length of Follow-up: 10.6 ± 3.6 years

            Number of Cases: 249

            Apparent protective effect of regular continued LTPA in middle age men on the risk of ischemic stroke.

              

            • Sex: Men

               
              

            • Age: 45-80

             

            Adjusted for age and smoking RR (95% CI) for total stroke by LTPA level

             

            Iceland

             

            • Characteristics: no history of Stroke

            PA assessment: Questionnaire for LTPA (h/wk) and type of activity (intensity), each divided into 3 groups

              

            Prospective cohort

             

            • Reykjavik Study

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.84 (0.63-1.13)

             
                

               • G3 = 0.73 (0.40-1.35)

             

            D & B score = 13

              

            LTPA summer/winter

              
               

            G1 = none

            Adjusted for age and smoking RR (95% CI) for ischemic stroke by LTPA level

             
               

            G2 = ≤ 5 h/wk

              
               

            G3 = ≥ 6 h/wk

              
                

               • G1 = 1.00 (referent)

             
               

            Type of Activity

               • G2 = 0.72 (0.51-1.01)

             
               

            G1 = none

              
                

               • G3 = 0.78 (0.41-1.48)

             
               

            G2 = low intensity

              
               

            G3 = high Intensity

              
                

            RR (95% CI) for total stroke by type of activity

             
               

            Outcome Measure: Total and ischemic Stroke

               • G1 = 1.0,0 (referent)

             
                

               • G2 = 0.75 (0.53-1.08)

             
                

               • G3 = 1.10 (0.78-1.57)

             
               

            Cox proportional HR

              
                

            RR (95% CI) for ischemic stroke by type of activity

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.72 (0.44-1.07)

             
                

               • G3 = 0.96 (0.64-1.44)

             

            Ellekjaer et al 2000 [256]

            To examine the association between different levels of LTPA and stroke mortality in middle-aged and elderly women.

            • n = 14,101

            Baseline 1984-1986: 2 self administered questionnaires and clinical measurements included in the screening program.

            Number of cases: 457

            This study demonstrates a consistent, negative association between PA and stroke mortality in women.

              

            • Sex: Women

               
              

            • Age: 50 yr

             

            Multivariate RR (95% CI), all age groups

             

            Norway

             

            • Characteristics: free from stroke at baseline

               
                

               • G1 = 1.00 (referent)

             

            Prospective cohort

               

               • G2 = 0.77

             
               

            PA assessment: Questionnaire for LTPA, divided into 3 groups

               • G3 = 0.52

             

            D & B score = 14

               

            Multivariate RR (95% CI), age 50--69 years

             
               

            G1 = low

             

            The most active women had approx. 50% lower risk of death from stroke compare to inactive women.

               

            G2 = medium

               • G1 = 1.00 (referent)

             
               

            G3 = high

               • G2 = 0.57

             
                

               • G3 = 0.42

             
               

            Outcome Measure: Death from stroke

            p = 0.0021

             
                

            Multivariate RR (95% CI), age 70-79 years

             
               

            Cox proportional HR

              
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.79

             
                

               • G3 = 0.56

             
                

            p = 0.0093

             
                

            Multivariate RR (95% CI), age 80-101 years

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.91

             
                

               • G3 = 0.57

             
                

            p = 0.1089

             

            Evenson et al 1999 [257]

            To examine the relationship between PA and ischemic stroke risk.

            • n = 14,575

            7.2 year follow up

            Number of Cases: 189

            PA was weakly associated with a reduced risk of ischemic stroke among middle aged adults.

              

            • Sex: Men and women

             

            Number of Dropouts: 0%

             
              

            • Age: 45-64 yr

            PA assessment: Questionnaire (Baecke questionnaire)

              

            USA

             

            • Atherosclerosis Risk in Communities Study

             

            Sport, Incidence of Ischemic Stroke

             

            Prospective cohort

               

            Multivariate adjusted RR (95% CI) by sport

             
               

            Outcome Measure:

              
               

            Ischemic Stroke

               • Q1 = 1.00 (referent)

             

            D & B score = 14

               

               • Q3= 0.83 (0.52-1.32)

             
               

            Multivariate Poisson and Cox proportional HR

              
                

            Multivariate adjusted RR (95% CI) by LTPA

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 =

             
                

               • Q3 = 0.89 (0.57-1.37)

             
                

            Multivariate adjusted RR (95% CI) by OPA

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 =

             
                

               • Q3 = 0.69 (0.47-1.00)

             

            Haheim et al 1993 [258]

            To determine the risk factors of stroke incidence and mortality.

            • n = 14,403

            Baseline Screening from May 1972- December 1973.

            HR (95% CI) for stroke incidence

            Increased LTPA is associated with a reduced risk of stroke incidence but not mortality.

              

            • Sex: Men

             

               • G1 = 1.00 (referent)

             
              

            • Age: 40-49 yr

             

               • G2 = 0.64 (0.38-1.08)

             

            Norway

              

            PA assessment: Questionnaire for LTPA, divided into groups

               • G3 = 0.36 (0.15-0.80)

             

            Prospective cohort

               

            HR (95% CI) for stroke mortality

             
               

            G1 = Sedentary

               • G1 = 1.00, (referent)

             
               

            G2 = Moderate

               • G2 = 0.82 (0.33-2.35)

             

            D & B score = 14

              

            G3 = Intermediate or Great

               • G3 = 0.29 (0.03-1.51)

             
               

            Outcome Measure: Incidence of stroke morbidity and mortality until study end date, December 31, 1984.

              
               

            Cox proportional HR

              

            Hu et al 2005 [259]

            To assess the relationship of different types of PA with total and type-specific stroke risk.

            • n = 47,721

            PA assessement: Mailed questionnaire for LTPA, OPA and commuting PA, divided into groups as follows:

            RR (95% CI) by LTPA, men

            A high level of LTPA reduces the risk of all subtypes of stroke. Daily active commuting also reduces the risk of ischemic stroke.

              

            • Sex: Men and women

             

               • G1 = 1.00 (referent)

             
                

            • G2 = 0.83

             

            Finland

             

            • Age: 25-64

             

               • G3 = 0.72

             
              

            • Characteristics: Healthy at baseline

             

            p < 0.001

             

            Prospective cohort

                 
               

            LTPA levels:

            RR (95% CI) by LTPA, women

             
               

            G1 = Low

               • G1 = 1.00 (referent)

             

            D & B score = 13

              

            G2 = Moderate

               • G2 = 0.86

             
               

            G3 = High

               • G3 = 0.75

             
                

            p = 0.007

             
               

            OPA:

              
               

            G1 = Light

            RR (95% CI) by LTPA, men and women

             
               

            G2 = Moderate

              
               

            G3 = Hard

              
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.85

             
               

            Commuting PA:

              
               

            G1 = Motorized or no work,

               • G3 = 0.73

             
               

            G2 = walking or cycling 1-29 min G3 = walking or cycling ≥ 30 min.

            p <0.001

             
                

            RR (95% CI) by OPA, men

             
                

            • Not significant

             
               

            Outcome Measure: Incidence of fatal or non-fatal stroke occurring during follow-up until end of 2003. Mean follow-up of 19 years.

              
                

            RR (95% CI) by OPA, women

             
                

            • Not significant

             
                

            RR (95% CI) by OPA, men and women

             
                

               • G1 = 1.00 (referent)

             
               

            Cox proportional hazard

               • G2 = 0.90

             
                

            • G3 = 0.87

             
                

            p = 0.007

             
                

            RR (95% CI) by commuting PA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.91

             
                

               • G3 = 0.85

             
                

            p = 0.047

             
                

            RR (95% CI) by commuting PA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.86

             
                

               • G3 = 0.85

             
                

            p = 0.018

             
                

            RR (95% CI) by commuting PA, men and women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.89

             
                

               • G3 = 0.85

             
                

            p = 0.002

             

            Kiely et al 1994 [260]

            To examine the influence of increased PA on stroke risk in members of the Framingham study cohort.

            • n = 1,897 men 2,299 women

            Baseline measurement in 1954-1955 and follow up in either 1968-1969 or 1971- 1972

            Multivariate adjusted RR (95% CI) at first examination, men (mean age 50 years)

            Medium and high levels of PA among men are protective against stroke relative to low levels.

              

            • Sex: Men and women

               

            USA

               

               • G1 = 1.00 (referent)

             
              

            • Age: 28-62 yr

             

               • G2 = 0.90 (0.62-1.31) p = 0.59

             

            Prospective cohort

             

            • Characteristics: Free from stroke

            PA assessment: Questionnaire for metabolic work done during a typical 24 hr period, divided into 3 groups

               • G3 = 0.84 (0.59-1.18) p = 0.31

             
                

            Multivariate adjusted RR (95% CI) at first examination, women (mean age 50 years)

            Protective effect of PA was slightly less for high levels of PA compared to medium levels for older men.

            D & B score = 12

                 
               

            G1 = Low

               • G1 = 1.00 (referent)

             
               

            G2 = Medium

               • G2 = 1.21 (0.89-1.63) p = 0.23

             
               

            G3 = High

               • G3 = 0.89 (0.60-1.31) p = 0.54

             
               

            Outcome Measure: Incidence of stroke, as defined by the first occurrence of atherothrombotic brain infarctions, cerebral embolism or other type of stroke, during 32 years of follow-up.

              
                

            Multivariate adjusted RR (95% CI) at second examination, men (mean age 63 years)

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.41 (0.24-0.89) p = 0.0007

             
                

               • G3 = 0.53 (0.34-0.84) p = 0.007

             
                

            Multivariate adjusted RR (95% CI) at second examination, women (mean age 64 years)

             
               

            Cox proportional HR

              
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.97 (0.64-1.47) p = 0.67

             
                

               • G3 = 1.21 (0.75-1.96) p = 0.43

             

            Krarup et al 2007 [261]

            To compare the reported level of PA performed during the week preceding an ischemic stroke with that of community controls.

            • n = 127 cases 301 controls

            PA assessment:

            Univariate OR (95% CI)

            Stroke patients are less physically active in the week preceding an ischemic stroke when compared to age and sex-matched controls. Increasing PASE score was inversly, log-linearly and significantly associated with OR for ischemic stroke.

               

            Questionnaire about PA 1 week prior to stroke (cases) and 1 week prior to questionnaire (controls), divided into PASE scores and quartiles

            PASE Score

             
              

            • Sex: Men and women

             

               • Q1 = 1.00 (referent)

             

            Denmark

               

               • Q2 = 0.51 (0.28-0.95)

             
              

            • Age: ≥ 40 yr

             

            • Q3 = 0.27 (0.14-0.54)

             

            Case control

             

            • Characteristics: Case: Stroke Patients (20% had history of Stroke), Controls: 4% had history of stroke

             

            • Q4 = 0.08 (0.03-0.20)

             

            D & B score = 14

              

            Q1 = 0-49

            Multivariate OR (95% CI) PASE Score

             
               

            Q2 = 50-99

              
               

            Q3 = 100-149

               • Q1 = 1.00 (referent)

             
               

            Q4 = 150+

               • Q2 = 0.53 (0.26-1.08)

             
                

               • Q3 = 0.27 (0.12-0.59)

             
               

            Outcome measure:

              
               

            Ischemic stroke

               • Q4 = 0.09 (0.03-0.25)

             
               

            Chi squared Kruskal-Wallis Statistics Multivariate conditional logistic regression

              

            Kurl et al 2003 [262]

            To examine the relationship of PF with subsequent incidence of stroke. Also to compare PF with conventional risk factors as a predictor for future stroke.

            • n = 2,011

            Baseline examinations conducted between March 1984 and December 1989 with average follow up period of 11 years

            Multivariate HR (95% CI), any stroke

            Low PF was associated with an increased risk of any stroke and ischemic stroke.

              

            • Sex: Men

             

               • Q1 = 1.00 (referent)

             
              

            • Age: 42, 48, 54 or 60 yrs

             

               • Q2 = 1.39 (0.70-2.77)

             

            Finland

               

               • Q3 = 1.32 (0.66-2.65)

             
              

            • Characteristics: Free from stroke or pulmonary disease

            • Kuopio Ischaemic Heart Disease Risk Factor Study

             

               • Q4 = 2.30 (1.18-4.06)

             

            Prospective cohort

               

            Trend p = 0.01

             
               

            PF assessment: Maximal exercise test on cycle ergometer. VO2 max (ml/kg/min) divided into quartiles

              
                

            Multivariate HR (95% CI), ischemic stroke

             

            D & B score = 14

                 
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.28 (0.56-2.94)

             
                

               • Q3 = 1.64 (0.74-3.65)

             
               

            Q1 = >35.3

              
                

               • Q4 = 2.40 (1.09-5.25)

             
               

            Q2 = 30.3-35.3

              
                

            Trend p = 0.01

             
               

            Q3 = 25.2-30.2

              
               

            Q4 = <25.2

              
               

            Outcome Measure: Stroke incidence

              
               

            Cox proportional HR

              

            Myint et al 2006 [263]

            To examine the association between a combination of OPA and LTPA with risk of subsequent stroke.

            • n = 22,602

            Baseline measurement in

            Model A: Used all 4 categories of PA

            Higher levels of PA assessed using a single simple pragmatic tool based on both OPA and LTPA is associated with reduced stroke risk.

              

            • Sex: Men

            1993-1997

            HR (95% CI), men and women

             
              

            • Age: 40-79 yr

             

               • G1 = 1.00 (referent)

             

            UK

             

            • Characteristics: Healthy at baseline

            PA assessment: Questionnaire for PA (includes LTPA and OPA) divided into 4 groups

               • G2 = 0.78 (0.61-1.00)

             
                

               • G3 = 0.66 (0.49-0.91)

             

            Prospective cohort

             

            • European Prospective Investigation in Cancer-Norfolk

             

               • G4 = 0.70 (0.49-0.99)

             
                

            p = 0.024

             

            D & B score = 11

              

            G1 = Inactive

            HR (95% CI), men

             
               

            G2 = moderately inactive

               • G1 = 1.00 (referent)

             
               

            G3 = moderately active

               • G2 = 0.75 (0.52-1.09)

             
               

            G4 = active

              
                

               • G3 = 0.55 (0.35-0.86)

             
                

               • G4 = 0.67 (0.43-1.05)

             
               

            Outcome Measure: Incidence of fatal and non fatal stroke.

              
                

            p = 0.41

             
                

            Women not significant p = 0.50

             
               

            Cox proportional HR

              
                

            Model B: Used 3 categories of PA (G3 and G4 combined combined)

             
                

            HR (95% CI), men and women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.78 (0.61-1.00)

             
                

               • G3 = 0.68 (0.52-0.88)

             
                

            p = 0.009

             
                

            HR (95% CI), men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.75 (0.52-1.09),

             
                

               • G3 = 0.61 (0.43-0.86)

             
                

            p = 0.019

             
                

            Women not significant p = 0.34

             

            Noda et al 2005 [264]

            To examine the impact of exercise on CVD (stroke) mortality in Asian populations.

            • n = 31,023 men, 42,242 women

            9.7 year follow up

            Number of Cases: 186 men, 141 women

            PA through walking and sports participation may reduce the risk of mortality from ischemic stroke

              

            • Sex: Men and women

            PA assessment: Questionnaire for PA (walking and sports participation (h/day), divided into quartiles:

            Number of Dropouts: 3.4%

             

            Japan

             

            • Age: 40 -79 yr

               
              

            • Ethnicity: Asian

             

            Multivariate adjusted HR (95% CI) by duration of walking PA, men

             

            Prospective cohort

                 
                

               • Q1 = 1.03 (0.63-1.69)

             
               

            Q1 = <0.5

               • Q2 = 1.00 (referent)

             

            D & B score = 13

              

            Q2 = 0.5

               • Q3 = 0.56 (0.35-0.91)

             
               

            Q3 = 0.6-0.9

               • Q4 = 0.71 (0.49-1.02)

             
               

            Q4 = >1.0

              
                

            Multivariate adjusted HR (95% CI) by duration of walking PA, women

             
               

            Outcome Measure: Death from ischemic stroke

              
                

               • Q1 = 1.38 (0.82-2.33)

             
                

               • Q2 = 1.00 (referent)

             
               

            Cox proportional HR

              
                

               • Q3 = 0.56 (0.32-0.97)

             
                

               • Q4 = 0.73 (0.48-1.13)

             
                

            Multivariate adjusted HR (95% CI) by sport PA, men

             
                

               • Q1 = 1.34 (0.86-2.08)

             
                

               • Q2 = 1.00 (referent)

             
                

               • Q3 = 1.22 (0.66-2.25)

             
                

               • Q4 = 0.84 (0.45-1.57)

             
                

            Multivariate adjusted HR (95% CI) by sport PA, women

             
                

               • Q1 = 1.07 (0.64-1.77)

             
                

               • Q2 = 1.00 (referent)

             
                

               • Q3 = 0.62 (0.25-1.58)

             
                

               • Q4 = 0.73 (0.31-1.70)

             

            Paganini-Hill and Barreto 2001 [265]

            To identify risk factors and preventative measures for stroke in elderly men and women.

            • n = 4,722 men, 8,532 women

            Baseline survey in 1981- 1982.

            Multivariate adjusted RR (95% CI) for total hemorrhagic occlusion by exercise, men

            Emphasized role of lifestyle modification in the primary prevention of stroke.

              

            • Sex: Men and women

               
               

            PA assessment: Questionnaire on amount of hours per day of exercise

               • Q1 = 1.00 (referent)

             

            USA

             

            Age: 44-101 yr

             

               • Q2 = 0.88

             
              

            • Characteristics: no previous history of stroke. Residence of a retirement community in Southern California

             

            Q3 = 0.83

             

            Prospective cohort

              

            G1 = <0.5

              
               

            G2 = <0.1

            Multivariate adjusted RR (95% CI) for total hemorrhagic occlusion by exercise, women

             
               

            G3 = 1+

              

            D & B score = 13

                 
               

            Outcome Measure: Incidence of hemorrhagic occlusion strokes up until December 31, 1998.

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.91

             
                

               • Q3 = 0.85

             
               

            Poisson Regression 40 year follow up

              

            Pitsavos et al 2004 [266]

            To investigate the interaction between PA in men with LVH on stroke mortality.

            • n = 489

             

            Number of cases: 67

            PA reduced the risk of stroke in men without LVH.

              

            • Sex: Men

               
               

            PA assessment: Questionnaire

            RR (95% CI)

             

            USA

             

            • Age: 40-59 yr

             

               • G1 = 1.00 (referent)

             
              

            • Characteristics: Those without LVH

            G1 = Sedentary

               • G2 = 0.64 (0.45-0.91)

             

            Prospective cohort

              

            G2 = Moderate

               • G3 = 0.72 (0.51-1.02)

             
              

            • Corfu Cohort (Greece) from Seven Countries Study

            G3 = Hard

              

            D & B score = 12

              

            Outcome Measure: Stroke mortality

              
               

            Cox proportional HR

              

            Sacco et al 1998 [267]

            To investigate the association between LTPA and ischemic stroke.

            • n = 369 case, 678 control

            Case Subjects were recruited during hospitalization, self referral or from monitoring non hospitalized stroke. Controls were eligible if they had never been diagnosed with stroke and were >39 years.

             

            LTPA was related to a decreased occurrence of ischemic stroke in elderly, multiethnic, urban subjects.

              

            • Sex: Men and women

             

            O R (95% CI) for duration of LTPA and stroke

             

            USA

                 
              

            • Age: > 39 yr

             

               • G1 = 1.00 (referent)

             

            Case control

             

            • Characteristics: Case Subjects: Diagnosed with first cerebral infarction after July 1, 1993. Control Subjects: Never diagnosed with stroke

             

               • G2 = 0.42

             
                

               • G3 = 0.35

             

            D & B score = 14

               

               • G4 = 0.31

             
               

            PA assessment:

              
               

            Questionnaire

              
               

            Divided into duration of LTPA (h/wk)

              
              

            • Northern Manhattan Stroke Study

               
               

            G1 = 0

              
               

            G2 = <2

              
               

            G3 = 2-<5

              
               

            G4 = ≥ 5

              
               

            Multivariate conditional logistic regression Baseline data collection from 1982-1983 in East Boston (MA), New Haven (CT) and Iowa and Washington counties (IA).

              

            Simonsick et al 1993 [268]

            To examine the association between recreational PA among physically capable older adults and incidence of selected chronic diseases and mortality over 3 and 6 years.

            • n = 1,815

             

            After 3 years Iowa

            No consistent relationship between PA and stroke was found after 3 or 6 years across all 3 population cohorts.

              

            • Sex: Men and women

               
              

            • Age: ≥ 65 yrs

             

            OR (95% CI) Stroke and activity level

             

            USA

             

            • Characteristics: Physically capable to do heavy work around the house, walk up and down a flight of stairs and walk a half mile without help.

             

               • T1 = 0.22 (0.08-0.61)

             
                

               • T2 = 1.05 (0.60-1.84)

             

            Prospective cohort

               

               • T3 = 1.00 (Referent)

             
               

            PA assessment: Questionnaire

              
                

            New Haven

             

            D & B score = 12

              

            T1 = High

            OR (95% CI) Stroke and activity level

             
               

            T2 = Moderate and

               • T1 = 1.06 (0.38-2.95)

             
               

            T3 = Inactive

               • T2 = 1.26 (0.54-2.92)

             
              

            • Established Populations for Epidemiologic Studies of the Elderly

             

               • T3 = 1.00 (Referent)

             
               

            Outcome Measure: Stroke incidence during 3 and 6 year follow-ups.

              
                

            East Boston

             
                

            OR (95% CI) Stroke and activity level

             
                

               • T1 = 0.59 (0.17-1.95)

             
               

            Logistic Regression

              
                

               • T2 = 1.08 (0.52-2.27)

             
                

               • T3 = 1.00 (Referent)

             
                

            After 6 years

             
                

            Iowa

             
                

            OR (95% CI) Stroke and activity level

             
                

               • T1 = 0.56 (0.31-1.00)

             
                

               • T2 = 0.97 (0.64-1.48)

             
                

               • T3 = 1.00 (Referent)

             
                

            New Haven

             
                

            OR (95% CI) Stroke and activity level

             
                

               • T1 = 1.05 (0.52-2.12)

             
                

               • T2 = 1.29 (0.72-2.32)

             
                

               • T3 = 1.00 (Referent)

             
                

            East Boston

             
                

            OR (95% CI) Stroke and activity level

             
                

               • T1 = 1.21 (0.56-2.61)

             
                

               • T2 = 1.73 (0.98-3.06)

             
                

               • T3 = 1.00 (Referent)

             

            Thrift et al 2002 [269]

            To examine whether intracerebral hemorrhage is associated with dynamic or static exercise.

            • n = 662

            PA assessment: Interview, divided into 3 groups: frequency of vigorous activity

            Number of Cases: 331

            Findings not significant after multivariate analysis.

              

            • Sex: Men and women

               
              

            • Age: 18-80 yr

             

            Multivariate OR (95% CI) by frequency of VPA

             

            Australia

             

            • Characteristics: Cases: first episode ofintracerebral hemorrhage Controls: Neighbours of cases

               
               

            G1 = Never

               • G1 = 1.00 (referent)

             

            Case control

              

            G2 = Rarely

               • G2 = 0.68 (0.36-1.27)

             
               

            G3 = Once or more per month

               • G3 = 0.66 (0.39-1.11)

             

            D & B score = 14

               

            p = 0.094

             
               

            OPA level

            Multivariate OR (95% CI) by OPA level

             
               

            G1 = Sedentary

               • G1 = 1.00 (referent)

             
               

            G2 = Light to moderate

               • G2 = 0.94 (0.59-1.48), p = 0.773

             
               

            G3 = Heavy

               • G3 = 1.18 (0.57-2.46), p = 0.650

             
               

            Outcome Measure: Intracerebral hemorrhage

              
               

            Multiple logistic regression

              

            D & B score, Downs and Black quality score; YR, years; wk, week; CVD, cardiovascular disease; G, groups; PA, physical activity; CHD, coronary heart disease; RR, risk ratio; 95% CI, 95% confidence interval; T, tertile; PF, physical fitness; MET, metabolic equivalent; Q, quartile or quintile; OPA, occupational physical activity; LTPA, leisure-time physical activity; HR, hazard ratio; VPA, vigorous physical activity; LVH, left ventricular hypertrophy.

            The data providing dose-response information is all observational in nature, involving both case control and cohort investigations. These studies (predominantly prospective cohort designs) included a total of 479,336 participants; averaging 17,753 subjects per study (range 428-73,265). There were a total of 12,361 reported cases of stroke (ranging per study from 32-2,863). The total length of study follow-up for the prospective cohort studies averaged 13.2 yr (ranging from 6-26 yr). The articles were published over a 14 yr period ranging from 1993 to 2007. These studies involved large samples of men and women from regions throughout the world including studies from the USA (11), UK (2), Iceland (1), Denmark (2), Norway (4), Netherlands (1), Finland (2), Japan (1), Australia (1) and Greece (1). Very few studies [69, 70] examined non-Caucasian participants.

            We found strong evidence that physical activity was associated with a reduced risk for stroke. The level of evidence was consistent with a Level 3A classification. We observed an average risk reduction of 31% across all studies (median = 29%). In comparison to cardiovascular disease, there was more variability in the risk reductions in stroke in the highest activity/fitness group. The quality of the investigations was also generally quite good with a mean (and median) Downs and Black score of 13 (range 11-15).

            The risk reductions appear to be even greater in studies that assessed physical fitness directly. For instance, in data from the Aerobics Center Longitudinal Study [71] the high fitness group (estimated peak METs = 13.1) and the moderate fitness group (estimated peak METs 10.5) had significantly lower risks of stroke mortality (68 and 63%, respectively) than the least fit men (estimated peak METs 8.5).

            A dose-response relationship did emerge when examining the literature. However, as illustrated by others this was extremely variable amongst studies and varied according to the type of stroke (ischemic or haemorrhagic) [52]. For instance, 12 studies (46%) revealed a dose-response relationship in one or more measures of occupational and/or leisure-time physical activity and the risk for stroke. It is difficult to determine the minimal and optimal physical activity dosage for the prevention of stroke. Brisk walking has been associated with a lower risk of total and ischemic stroke [72]. In the Harvard Alumni study, the risk of stroke was lower at a weekly energy expenditure of 4.2-8.4 MJ/wk (1000-1999 kcal/wk) (RR = 0.76 (95% CI, 0.59 to 0.98)). With expenditures of 8.4-12.6 MJ/wk (2000-2999 kcal/wk) the RR dropped to 0.54 (0.38 to 0. 76) [73]. Thus, the recommended daily expenditure of Canada's physical activity guidelines is sufficient to reduce the risk for stroke. Further research is required to clearly determine the risk reductions at exercise volumes less than 4.2 MJ/wk (1000 kcal/wk).

            In summary, the results of these studies (taken as a whole) indicate that occupation- and leisure time-related physical activity are inversely related to the risk for stroke. Both physically active men and women have a lower risk of stroke, and it appears that this benefit may be present for both ischemic and haemorrhagic stroke [74]. The relationship between physical activity and stroke appears to be consistent between men and women. Unfortunately, relatively limited data exists in non-Caucasian populations.

            Recommendation #3

            For a reduced risk of stroke, it is recommended that individuals should participate in 30 min or more of moderate to vigorous exercise on most days of the week. Brisk walking appears to be protective against the development of stroke. It remains to be determined whether lower volumes of physical activity lead to a reduced risk for stroke. [Level 3, Grade A]

            Primary Prevention of Hypertension

            A total of 6287 citations were identified during the electronic database search (Figure 6). Of these citations, 4054 were identified in MEDLINE, 1360 in EMBASE, 253 in Cochrane, and 620 in the CINAHL/SportDiscus/PsychInfo search. A total of 40 duplicates were found, leaving a total of 6247 unique citations. A total of 6167 articles were excluded after scanning, leaving a total of 80 articles for full review. An additional five articles were found through cross-referencing and the reviewers' personal files. From these articles 72 were excluded after full review for the following reasons: weak design (n = 4), did not contain three levels of physical activity or not possible to determine dose-response relationship (n = 19), reviews, summaries, meta-analyses (n = 8), not dealing with hypertension (n = 2), only reported on changes in blood pressure (n = 27), clinical population (n = 7), and other (n = 6). Therefore, a total of 12 articles were included in the systematic review of the literature regarding the relationship between physical activity and the primary prevention of hypertension. The majority of the literature examining the dose-response (for at least three levels of physical activity/fitness) involved prospective cohort analyses (83%).
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig6_HTML.jpg
            Figure 6

            Results of the Literature Search for Hypertension.

            As shown in Table 14, 12 investigations examined the dose-response (i.e., three or more levels) relationship between physical activity and the incidence of hypertension. This involved a total of 112,636 participants, averaging 10,240 subjects per study (range 1,243-41,837). There were a total of 11,441 reported cases of hypertension (ranging per study from 118-2,936). The total length of study follow-up averaged 8.6 yr (ranging from 0-16 yr). The articles were published over a 24 yr period ranging from 1983 to 2007.
            Table 14

            Studies examining the relationship between physical activity and hypertension.

            Publication Country Study Design Quality Score

            Objective

            Population

            Methods

            Outcome

            Comments and Conclusions

            Rankinen et al 2007 [75]

            To investigate the contributions of DNA sequence variation in candidate genes, PF and BMI, as well as their interactions to the incidence of hypertension.

            • n = 629 cases; 605 controls

            10 year follow up

            PF showed the strongest association with HTN risk among all subjects as well as sex-specific models. Each 1- MET increment in PF was associated with 19% (12- 14%), 16% (9-22%), 32% (17- 45%) risk reduction in all subjects, men and women respectively.

            PF is a significant predictor of the risk of hypertension.

            USA

             

            • Sex: Men and women

            All subjects required to have 2 clinic visits at least 2 years apart.

              

            Case control

             

            • Age: Case: 43.3 (9.2) yr Control: 42.7 (8.9) yr

            PF assessment: treadmill test (Blake protocol)

              

            D & B score = 13

             

            • Characteristics: Healthy with BP 134/86 mmHg or less at their first clinic visit. Cases: those who developed hypertension during the follow-up period. Controls were those who did not develop hypertension

            Outcome measure: Incidence of hypertension during follow-up. Incident cases of hypertension were defined as physician diagnosed hypertension with medication or SBP ≥ 140 mmHg and/of DBP ≥ 90 mmHg t-tests and chi-square tests Logistic regression modelling

            When divided into quartiles on the basis of sex specific MET cut-offs, the third and fourth quartiles had a 58% (41-71%) and 63% (47-75%) lower risk of hypertension compared to the 1 st quartile.

             

            Pereira et al 1999 [76]

            To examine PA and incident hypertension in men and women.

            • n = 7,459

            PA Assessment: Questionnaire for leisure, sport and work index, divided into quartiles

            White Men

            There is an inverse association between PA and incident hypertension in White middle aged men. White men in the highest quartiles of sport and leisure activity had statistically significant reductions in the odds of developing hypertension of 23 and 34% respectively, compared to men in the lower quartiles.

            USA

             

            • Sex: Men and women

            Q1 = Lowest

            Leisure Index Model 1

             

            Prospective cohort

             

            • Age: 45-65 yr

            Q2

            • Q1 = 1.00 (referent)

             

            D & B score = 12

             

            • Characteristics: No history of angina, MI, evidence of MI, angioplasty or other CV surgery or hypertension

            Q3

            • Q2 = 0.95 (0.70-1.28)

             
              

            • Atherosclerosis Risk in Communities Study

            Q4 = Highest

            • Q3 = 0.83 (0.63-1.09)

             
               

            Model 1 adjusted for: Age, education, baseline BP and study centre

            • Q4 = 0.64 (0.46-0.89)

             
               

            Model 2 adjusted for: Covariates in model 1 and smoking, alcohol consumption, parental history of hypertension, energy, sodium, potassium and caffeine intake, BMI, waist to hip ratio, menopausal status and hormone use

            Trend p = 0.01

             
               

            Outcome Measure: Incidence of hypertension as defined as a SBP 140 mmHg and/or a DBP 90 mmHg or use of antihypertensive medications.

            Leisure Index Model 2

             
               

            Unconditional logistic regression Orthogonal polynomial coefficients

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 0.99 (0.72-1.35)

             
                

            • Q3 = 0.86 (0.65-1.13)

             
                

            • Q4 = 0.66 (0.47-0.94)

             
                

            Trend p = 0.01

             
                

            Women

             
                

            Sport Index Model 1

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 1.26 (0.78-2.05)

             
                

            • Q3 = 1.06 (0.61-1.84)

             
                

            • Q4 = 1.92 (1.12-3.29)

             
                

            Trend p = 0.04

             
                

            Men

             
                

            Sport Index Model 1

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 1.23 (0.91-1.66)

             
                

            • Q3 = 0.92 (0.70-1.22)

             
                

            • Q4 = 0.74 (0.54-1.02)

             
                

            Trend p = 0.02

             
                

            Sport Index Model 2

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 1.26 (0.93-1.71)

             
                

            • Q3 = 0.95 (0.71-1.26)

             
                

            • Q4 = 0.77 (0.55-1.08)

             
                

            Trend p = 0.05

             

            Haapanen et al 1997 [77]

            To assess the association between PA and hypertension.

            • n = 732 men; 796 women

            10 year follow up (1980 baseline)

            Age adjusted incidence rates ofhypertension Total energy expenditure High as referent:

            Increased EE during LTPA and increased intensity of these activities were associated with reduced risk for incident hypertension (age adjusted) in men but not women.

            Finland

             

            • Sex: Men and women

            PA assessement: Questionnaire for EE (kcal/wk), divided into tertiles

              

            Prospective cohort

             

            • Age: 35-65 years

            Male

            Male:

             

            D & B score = 11

             

            • Characteristics: Free of hypertension at baseline. Excluded those unable to participate in regular PA due to poor health

               T1 = Low = 0-1100

            • T1 = 1.00 (referent)

             
               

               T2 = Medium = 1101-1900

            • T2 = 1.66

             
               

               T3 = High >1900

            • T3 = 1.73

             
                

            Trend p = 0.021

             
               

            Female

            Female:

             
               

               T1 = Low = 0-900

            • T1 = 1.00 (referent)

             
               

               T2 = Medium = 901-1500

            • T2 = 0.94

             
               

               T3 = High = >1500

            • T3 = 1.16

             
               

            Outcome measure: Incidence of hypertension through self reported diagnosis and death certificates

            Trend p = 0.648

             
               

            Cox proportional HR

              

            Paffenbarger et al 1983 [78]

            To examine the relationship of student and alumnus PA patterns and other characteristics with incident hypertension.

            • n = 14,998

            PA Assessment: Questionnaire for PA based on number of stairs ascended, blocks walked and hours per week of light and vigorous sports play, yard work etc.

            There was no significantly reduced risk for hypertension in men who climbed 50 plus stairs per day (compared to < 50 stairs); who walked 5 plus blocks per day (compared to < 5 blocks); or who played light sports (compared to those who did not).

            Contemporary vigorous exercise was inversely related to hypertension risk.

            USA

             

            • Sex: Men

               

            Prospective cohort

             

            • Age: 35-74 yr

            Outcome measure: Diagnosis of hypertension by physicians using criteria of SBP > 160 mmHg and/or DBP > 95 mmHg

            The 59% of men who did engage in vigorous sports were at 35% greater risk of hypertension than the 41% who did not.

             
                

            RR = 1.35

             
                

            Trend p = <0.001

             

            D & B score = 12

             

            • Characteristics: free of hypertension Harvard Alumni Study

            Multivariate estimates

            Alumni on the low side of the physical activity index (< 2000 kcal/wk) had a 30% increased risk of hypertension then those ≥ 2000 kcal/wk.

             
                

            RR = 1.30

             
                

            Trend p = 0.004

             

            Paffenbarger et al 1997 [79]

            To investigate the quantity and intensity of energy expenditure required to delay hypertension and prevent premature death.

            • n = 6,390

            PA Assessment: Questionnaire for weekly sports play, divided into tertiles

            RR (95% CI)

            Lack of vigorous sports play independently increased the risk of developing hypertension.

            USA

             

            • Sex: Men

            T1 = None

            • T1 = 1.00 (referent)

             

            Prospective cohort

             

            • Age: 45-84 yr

            T2 = Light Only (< 4.5 METs)

            • T2 = 1.04 (0.77-1.40)

             

            D & B score = 12

             

            • Characteristics: Free of hypertension, CHD, diabetes, COPD and potentially malignant cancer in 1977

            T3 = Moderately vigorous (≥ 4.5 METs)

            • T3 = 0.77 (0.62-0.96)

             
              

            • Harvard Alumni Study

            Outcome measure: Incident hypertension

            Trend p = 0.004

             

            Hu et al 2004 [81]

            To discover whether regular PA can reduce the risk of hypertension in normal weight and overweight men and women.

            • n = 8,302 men; 9,139 women

            11 year follow up

            Multivariate adjusted HR (95% CI), men

            Regular PA can reduce the risk of hypertension. The protective effect of PA was observed in both sexes regardless of level of obesity.

            Finland

             

            • Sex: Men and women

            PA assessement: Questionnaire for OPA, LTPA and commuting PA, divided into tertiles

            • T1 = 1.00 (referent)

             

            Prospective cohort

             

            Age: 25-64 yr

            T1 = Low

            • T2 = 0.63

             

            D & B score = 13

             

            Characteristics: Healthy and free of hypertension at baseline

            T2 = Medium

            • T3 = 0.59

             
               

            T3 = High

            Trend p = < 0.001

             
               

            Outcome Measure: Incidence of drug treated hypertension

            Multivariate adjusted HR (95% CI), women

             
               

            Cox proportional HR

            • T1 = 1.00

             
                

            • T2 = 0.82

             
                

            • T3 = 0.71

             
                

            Trend p = 0.005

             

            Gu et al 2007 [82]

            To determine the 8-year incidence of HTN and its risk factors among Chinese adults.

            • n = 10,525

            Baseline Examination in 1991 with 8 year follow up

            RR (95% CI), men

            Increasing PA has the potential to reduce incidence of hypertension.

            China

             

            • Sex: Men and women

            PA assessment: Questionnaire administered by trained staff, divided into groups

            • G1 = 1.00 (referent)

             

            Prospective cohort

             

            Age: ≥ 40 yr

            G1 = Low

            • G2 = 1.12 (0.86-1.46)

             

            D & B score = 13

             

            Characteristics: Healthy and free from hypertension at baseline.

            G2 = Medium

            • G3 = 1.27 (1.10-1.47)

             
               

            G3 = High

            RR (95% CI), women

             
               

            Outcome measure: HTN as defined at SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or current use of antihypertensive medication

            • G1 = 1.00 (referent)

             
               

            t-tests, chi squared tests, Cochran-Armitage modeling, Modified Poisson approach

            • G2 = 1.14 (0.98-1.34)

             
                

            • G3 = 1.22 (1.02-1.45)

             

            Hayashi et al 1999 [83]

            To investigate the association of the duration of the walk to work and LTPA with the risk for hypertension.

            • n = 6,017

            PA assessment: Questionnaire on health related behaviours and exercise Walk time to work

            RR (95% CI) Frequency walk time to work (minutes

            The duration of walk to work was associated with a decreased risk of hypertension even after adjustment.

            Japan

             

            • Sex: Men

            T1 = 0-10 min

            • T1 = 1.00 (referent)

            Regular PA (at least once weekly) was inversely related to the risk of incident hypertension

            Prospective cohort

             

            • Age: 35-60 yr

            T2 = 11-20 min

            • T2 = 0.65 (0.47-0.90)

             

            D & B score = 12

             

            • Characteristics: Free from HTN at baseline. All employees at gas company in Osaka Japan. All had sedentary jobs.

            T3 = ≥ 21 min

            • T3 = 0.72 (0.59-0.88)

             
               

            Outcome measure: Diagnosed with hypertension (as defined by a SBP ≥ 160 mmHg, a DBP ≥ 95 mmHg, or use of antihypertensive medication)

            Trend p = < 0.001

             
               

            Cox proportional HR

              

            Nakanishi et al 2005 [84]

            To examine the relationship of overall PA to the risk of developing hypertension in normotensive Japanese male office workers over a 7 year observation period.

            • n = 2,548

            7 year follow up

            Multivariate adjusted RR (95% CI) by PA level only

            The rate of rise in both SBP and DBP in each follow-up year decreased with higher EE and that the risk of developing hypertension decreased in a dose dependent manner with higher daily life activity level.

            Japan

             

            • Sex: Men

             

            Q1 = 1.00 (referent)

            Analysis stratified by the presence of or absence of a risk factor showed the negative association of daily life activity with the risk of developing hypertension for men at both low and high risk. This tendency was also observed among men in all 3 categories of normotension.

            Prospective cohort

             

            • Age: 35-59 yr

            PA assessment: 1-day activity record and reported the type and frequency on a weekly basis of LTPA, divided into quartiles (kcal/kg/d)

            Q2 = 0.84 (0.72-0.98)

             

            D & B score = 12

             

            • Characteristics Healthy at baseline. No hypertension or CHD. All office workers for a Japanese company

            • Q1 = <33.3

            • Q3 = 0.75 (0.63-0.88)

             
               

            • Q2 = 33.3-36.9

            • Q4 = 0.54 (0.45-0.64)

             
               

            • Q3 = 37.0-40.3

            Trend p = < 0.001

             
               

            • Q4 = 40.4

            Multivariate adjusted RR (95% CI) by PA level, low normal BP

             
               

            3 categories of normotensive BP Low Normal: SBP < 120, DBP < 80 Normal: SBP 120-130, DBP 80- 85 High Normal: SBP 130-139 DBP 85-89

            • Q1 = 1.00 (referent)

             
               

            3 categories of normotensive BP Low Normal: SBP < 120, DBP < 80 Normal: SBP 120-130, DBP 80- 85 High Normal: SBP 130-139 DBP 85-89

            • Q2 = 0.70 (0.47-1.05)

             
               

            Cox proportional hazard model

            • Q3 = 0.55 (0.37-0.83)

             
                

            • Q4 = 0.43 (0.28-0.65)

             
                

            Trend p = <0.001

             
                

            Multivariate adjusted RR (95% CI) by PA level, normal

             
                

            BP

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 0.89 (0.68-1.16)

             
                

            • Q3 = 0.69 (0.52-0.91)

             
                

            • Q4 = 0.50 (0.37-0.68)

             
                

            Trend p = <0.001

             
                

            Multivariate adjusted RR (95% CI) by PA level, high normal BP

             
                

            • Q1 = 1.00 (referent)

             
                

            • Q2 = 0.86 (0.69-1.07)

             
                

            • Q3 = 0.88 (0.69-1.11)

             
                

            • Q4 = 0.60 (0.46-0.78)

             
                

            Trend p = 0.001

             

            Foy et al 2006 [85]

            To examine whether insulin resistance is associated with the effect of vigorous or moderate PA on baseline BP.

            • n = 1,599

            Baseline examination in 1992-1993

            Unadjusted OR (95% CI)

            Participants who meet or exceed current caloric expenditure recommendations for VPA demonstrate significantly less hypertension than do sedentary or underactive individuals.

            USA

             

            • Sex: Men and women

            PA assessment: VPA over the past year was determined via a 1-year recall of physical activity (kcal/d), divided into 3 groups

            • T1 = 1.00 (referent)

             

            Cross sectional

             

            • Age: 40-69 yr

            • T1 = O

            • T2 = 0.69 (0.53-0.88)

             

            D & B score = 12

             

            • Characteristics: Community dwelling adults

            • T2 = 1-149 kcal/day

            • T3 = 0.57 (0.45-0.74)

             
              

            • Insulin Resistance Atherosclerosis Study

            • T3 = >150 kcal/day

            • Trend p = < 0.001

             
                

            Adjusted OR (95% CI)

             
                

            • T1 = 1.00 (referent)

             
                

            • T2 = 0.82 (0.62-1.09)

             
                

            • T3 = 0.73 (0.55-0.98)

             
                

            Trend p = 0.004

             

            Folsom et al 1990 [270]

            To examine the relationship between fat distribution and the 2-yr incidence of hypertension and stroke.

            • n = 41,837

            Baseline mailed survey in 1986: Pa assessment: Questionnaire for LTPA

            • 978 cases

            High PA reduced the risk of hypertension only before adjusting for other factors.

            USA

             

            • Sex: Women

            T1 = Low

            Age Adjusted RR (95% CI)

             

            Prospective cohort

             

            • Age: 55-69 years (yr)

            T2 = Medium

            • T1 = 1.00 (referent)

             

            D & B score = 12

             

            • Characteristics: All free of HTN at baseline

            T3 = High

            • T2 = 0.9 (0.7-1.1)

             
               

            Mantel-Haenszel method

            • T3 = 0.7 (0.6-0.9)

             
               

            Multiple logistic regression

              

            Levenstein et al 2001 [271]

            To examine the effects of a variety of psychosocial factors on the development of HTN in men and women in the general population.

            • n = 1,031 men, 1,326 women

            Questionnaires in 1965 and 1974, cohort followed until 1994

            LTPA predictor of hypertension OR (95% CI)

            Risk of HTN was reduced with increases in LTPA in women.

            USA

             

            • Sex: Men and women

            PA assessment: LTPA rated on a scale of 0-16 points and analysed as a continuous variable

            • All Subjects: 0.94 (0.91-0.97)

             

            Prospective cohort

             

            • Characteristics: Free of hypertension at baseline

            Outcome measure: Incidence of hypertension (defined as those who are taking antihypertensive medications)

            • Women: 0.90 (0.87-0.94)

             

            D & B score = 13

             

            • Alameda cohort study

            Logistic regression analysis

            • Men: 0.98 (0.94-1.02)

             

            D & B score, Downs and Black quality score; YR, years; PF, physical fitness; BMI, body mass index; MET, metabolic equivalent; PA, physical activity; MI, myocardial infarction; G, groups; Q, quartile or quintile; 95% CI, confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure; EE, energy expenditure; kcal/wk, kilocalories per week; T, tertile; RR, risk ratio; HR, hazard ratio; CHD, coronary heart disease; COPD, chronic obstructive pulmonary disease; OPA, occupational physical activity; LTPA, leisure-time physical activity; BP, blood pressure; kcal/day, kilocalories per day.

            All studies reviewed demonstrated positive effects of physical activity on the risk for hypertension. Of these studies all (7; 58%) revealed an inverse and graded relationship between hypertension and at least one measure of physical activity or fitness. Across all studies, when comparing the most active/fit group versus the least active/fit group we found an average RR of 0.68 (median = 0.70, range 0.37 to 0.90). Therefore, we observed that physical activity/fitness was associated with an average risk reduction of 32% for hypertension. It should be noted that the study [75] demonstrating the largest risk reduction (63%) evaluated cardiorespiratory fitness directly during a maximal treadmill test. This supports research (as discussed previously) which indicates that physical fitness is a better predictor of chronic disease than physical activity [6, 18, 19, 32, 33]. Taken as a whole, the level of evidence can be classified as Level 3A. The quality of studies was generally good with a mean Downs and Black score of 11 (median = 11, range = 10-12).

            Five studies showed variable results (i.e., no clearly defined dose-response) while generally supporting the inverse relationship between physical activity/fitness and hypertension [7680]. The variability in the response appears to be the result of different activity/fitness classifications and/or differing subject populations. For instance, some studies revealed that the dose-response relationships differed between genders and/or ethnicities [76, 77]. Pereira et al. [76] revealed a 30% reduction in the risk for hypertension in the most active white men. There were graded dose-response relationships between indices of both leisure and sport activities in the white men.

            However, there was a lack of association between physical activity and hypertension in white women and African American men and women. Similarly, Haapenen et al. [77] revealed a stronger association in men than in women. However, it should be noted clearly that other studies included in this systematic review evaluated women demonstrating a graded response [81]. Moreover, several studies were conducted with non-Caucasian populations and demonstrated a dose-dependent benefit [8285]. In fact, data was obtained from varied regions of the world including USA (7), Japan (2), China (1), and Finland (1). Therefore, there is evidence to suggest that the protective effects of physical activity with respect to hypertension are transferable to women and non-Caucasian populations. However, further research is clearly warranted that examines the relationship between physical activity and hypertension in persons of different ethnicities. Moreover, further research is needed to determine the effects of impact of socio-economic status on the observed relationships.

            Some studies have indicated that vigorous activity is required to reduce the risk for hypertension. For instance, Paffenbarger [78] revealed that Harvard Alumni who did not engage in vigorous sports play were at a 35% higher risk for developing hypertension. However, there was no difference in the risk for hypertension in men who climbed >50 stairs per day, walked more than 5 city blocks daily, or engaged in light sports only. Similarly, the Paffenbarger and Lee [79] study revealed that moderately vigorous sports play was associated with a lower risk for hypertension, but physical activity (kcal/wk), walking distance (km/wk) and the amount of stairs climbed (floors/wk) were not significant predictors of the risk for hypertension. Collectively, this research group concluded that these findings highlighted the importance of the intensity of effort.

            However, it should be noted that many of the studies in our systematic review observed the protective effect with moderate intensity physical activities. Findings from randomized controlled trials have also provided strong evidence that moderate intensity aerobic exercise is sufficient to reduce blood pressure and the risk for hypertension, particularly in at risk individuals [86, 87]. The American College of Sports Medicine [88] recently advocated that to prevent hypertension, individuals should exercise on most, and preferably all, days of the week at a moderate intensity, for 30 min or more per day (continuous or accumulated). They also recommended supplementing endurance type activities with resistance exercise. This is supported by research indicating that moderate intensity resistance training can reduce blood pressure [89]. Collectively, this research and our current summary of the dose-response literature indicates that physical activity levels that are of a moderate to vigorous intensity are sufficient to lead to marked reductions in the risk for hypertension.

            Implications

            The impact of hypertension on North American society is enormous. In the US, 31% of non-institutionalized adults over the ages of 20 are currently thought to have hypertension [90]. In Canada, approximately 20% of adults report a diagnosis of hypertension including over 4 million Canadians [9193]. It has been estimated that a 55 yr old Canadian with normal blood pressure has a greater than 90% chance of developing hypertension before the age of 80 yr [92]. The primary prevention of hypertension is of paramount importance to the attenuation of the risks and costs associated with hypertension and related comorbidities.

            There is clear evidence that routine physical activity and/or increased physical fitness reduce greatly the risk for hypertension in both normotensive and hypertensive individuals [18, 19]. Extensive research has been conducted in the area including numerous prospective trials and various randomized controlled trials. Numerous reviews of the literature (of epidemiological and randomized controlled trials) have supported an inverse relationship between physical activity/fitness and in the incidence of hypertension [20, 87, 89, 94102]. In a recent systematic review of the prospective literature, Katzmarzyk and Janssen (2004) calculated that physically inactive individuals were at a 30% higher risk for hypertension (RR = 1.30 (95% CI = 1.16-1.46)) with a population attributable risk of 13.8% in Canada [20]. Acute bouts of exercise have also been shown to lead to transient changes in blood pressure that are potentially of health benefit [98]. For instance, blood pressure is often reduced after a single exercise session for 12-22 hr [88, 103].

            It is clear that routine physical activity is effective in both the primary and secondary prevention of hypertension. However, the optimal dosage of physical activity/exercise remains somewhat unclear. Our review of the literature examined critically the relationship between multiple levels of physical activity/fitness and the incidence of hypertension (in individuals without diagnosed hypertension). As identified above this evidence was compelling supporting the protective effects of habitual physical activity in the primary prevention of hypertension.

            Recommendation #4

            For a reduced risk for hypertension, it is recommended that individuals should participate in 30 min or more of moderate to vigorous exercise on most days of the week. [Level 3, Grade A]

            Primary Prevention of Colon and Breast Cancer

            Colon Cancer

            In our systematic search of the colon cancer literature, a total of 252 citations were identified during the electronic database search (Figure 7). Of these citations, 83 were identified in MEDLINE, 44 in EMBASE, 25 in Cochrane, and 100 in the CINAHL/SportDiscus/PsychInfo search. A total of 15 duplicates were found, leaving a total of 237 unique citations. A total of 164 articles were excluded after screening, leaving a total of 73 articles for full review. From these articles 47 were excluded after full-text review leaving 26 articles for inclusion, and an additional 7 articles were added from the authors' personal files. The reasons for exclusion included non-experimental/weak design (n = 8), reviews, summaries, meta-analyses (n = 13), editorial/comment (n = 3), not dealing specifically with colon cancer (n = 4), did not contain three levels of physical activity or not possible to determine dose-response relationship (n = 9), and other (n = 10). Therefore, a total of 33 articles were included in the systematic review of the literature regarding the relationship between physical activity and the primary prevention of colon cancer.
            http://static-content.springer.com/image/art%3A10.1186%2F1479-5868-7-39/MediaObjects/12966_2009_Article_345_Fig7_HTML.jpg
            Figure 7

            Results of the Literature Search for Colon Cancer.

            These studies involved a total of 1,433,103 participants; averaging 43,427 participants per study (range 142-413,044). There were a total of 17,959 reported cases of colon cancer (ranging per study from 93-1,993). The total length of study follow-up for the prospective cohort studies averaged 10.7 yr (ranging from 4-26 yr). The articles were published over a 23 yr period ranging from 1985 to 2008. These studies involved large samples of men and women from regions throughout the world.

            A dose-dependency of this relationship was present in the majority of the studies. When comparing the most active/fit group versus the least active/fit group we found a mean risk reduction of 30% (median = 32%) across all studies. The most compelling literature was that which evaluated the relationship between moderate-to-vigorous leisure time physical activity. Based on the literature reviewed and the volume of activity assessed it would appear that Canada's guidelines for physical activity are sufficient to lower the risk for the development of colon cancer in asymptomatic adults. The level of evidence would be considered to be Level 2A. The studies were generally of a higher quality with a mean Downs and Black score of 13 (median = 14, range = 11-15).

            It should be noted that there was considerable variability in the findings and conclusions of the studies (Table 15). As discussed later, the literature was further confounded by the fact that the relative risks associated with physical activity were often controlled (through multivariate analyses) for various potential confounding factors, which may actually inappropriately decrease the level of risk reduction associated with physical activity [31]. Moreover, similar to other chronic conditions this literature was limited greatly by the lack of consistent physical activity assessment and description. In many instances, it was difficult to determine the actual absolute volume and/or intensity of activity for each category of comparison. However, despite these limitations the results of these studies (taken as a whole) indicate that both occupation- and leisure time-related physical activity are inversely related to the risk of colon cancer.
            Table 15

            Studies examining the relationship between physical activity and colon cancer.

            Publication Country Study Design Quality Score

            Objective

            Population

            Methods

            Outcome

            Comments and Conclusions

            Hou et al 2004 [272]

            To examine the effect of various forms of PA on colon cancer risk, with particular attention to commuting PA.

            • n = 931 case, 1,552 control

            PA assessment: Interview for the following variables

               • Number of cases: 931

            Regular frequent PA over a long period of time reduces risk of CC.

            China

             

            • Sex: Men and women

             

            Multivariate OR (95% CI) by OPA, men

             
                

               • G1 = 1.00 (referent)

             

            Case control

             

            • Age: 30-74 yr

            OPA (kJ/min)

               • G2 = 1.23 (0.93-1.64)

             

            D & B score = 14

             

            • Characteristics: Case: diagnosed with CC. controls: selected randomly from residents of urban Shanghai.

            G1 = <8

               • G3 = 0.81 (0.59-1.19)

             
               

            G2 = 8-12

            p = 0.10

             
               

            G3 = >12

              
               

            Commuting PA (MET hr/wk)

            Multivariate OR (95% CI) by OPA, women

             
               

            G1 = <48.3

               • G1 = 1.00 (referent)

             
               

            G2 = 48.3-94.3

               • G2 = 0.96 (0.69-1.16)

             
               

            G3 = >94.3

               • G3 = 0.64 (0.39-1.02)

             
                

            p = 0.009

             
               

            LTPA (MET hr/wk)

            Multivariate OR (95% CI) Commuting PA, men

             
               

            G1 = < 9.2

               • G1 = 1.00 (referent)

             
               

            G2 = 9.2-13.6

               • G2 = 1.11 (0.31-1.23)

             
               

            G3 = >13.6

               • G3 = 0.52 (0.27-0.87)

             
               

            Outcome Measure: incident CC

            p<0.001

             
               

            Multiple logistic regression

            Multivariate OR (95% CI) Commuting PA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.87 (0.42-1.52)

             
                

               • G3 = 0.56 (0.21-0.91)

             
                

            p = 0.007

             
                

            Multivariate OR (95% CI) LTPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.17 (0.13-1.95)

             
                

               • G3 = 0.72 (0.41-1.07)

             
                

            p = 0.06

             
                

            Multivariate OR (95% CI) LTPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.03 (0.41-1.59)

             
                

               • G3 = 0.84 (0.13-2.25)

             
                

            p = 0.15

             

            Boutron-Ruault et al 2001 [273]

            To determine which step of the adenoma-carcinoma pathway was influenced by OPA and recreational PA.

            • n = 480

            PA assessment: Questionnaire and classified into 3 groups

            Number of cases: 171

            A sedentary lifestyle was associated with a high risk of CC.

            France

             

            • Sex: Men and women

            G1 = Low

            Age and gender adjusted OR (95% CI), OPA

             

            Case control

             

            • Age: 30-79 years

            G2 = Medium

            • G1 = 1.00 (referent)

             

            D & B score = 13

             

            • Characteristics: Cases had 1stdiagnosis of colorectal adenoma, controls were polyp free.

            G3 = High

            • G2 = 1.3 (0.8-2.0)

             
                

            • G3 = 0.5 (0.3-0.9)

             
                

            p = 0.005

             
               

            Outcome Measure: Incident CC

              
               

            Multiple logistic regression

            Age and gender adjusted OR (95% CI), LTPA

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.7 (0.4-1.1)

             
                

            • G3 = 0.3 (0.2-0.5)

             
                

            p = <0.0001

             
                

            Age and gender adjusted OR (95% CI), Global PA

             
                

            • G1 = 1.00 (referent)

             
                

            • G2 = 0.8 (0.5-1.2)

             
                

            • G3 = 0.3 (0.2-0.6)

             
                

            p = 0.0003

             

            Brownson et al 1991 [274]

            To investigate the risks of 16 cancer types in relation to OPA.

            • n = 17,147

            PA assessment: Medical records and classified into 3 groups:

            Number of cases: 1,838

            OPA is inversely related to risk of CC.

              

            • Sex: Men

             

            Multivariate OR (95% CI)

             

            USA

             

            • Age: ≥ 20 yr

            OPA

            G1 = 1.00 (referent)

             
              

            • Characteristics: White, working

            G1 = Low - Activity required <20% of time

            G2 = 1.2 (1.0-1.5)

             

            Case controll

              

            G2 = Moderate - Activity required 20-80% of time

            G3 = 1.1 (1.0-1.3)

             

            D & B score = 15

              

            G3 = High - Activity required >80% of time

            p = 0.05

             
               

            Outcome Measure: CC

              
               

            Maximum likelihood estimates

              

            Calton et al 2006 [275]

            To examine the relationship between PA and colon cancer risk in women.

            • n = 31,783

            11 year follow up

            Number of cases: 243

            Results do not support the hypothesis that PA is related to a lower incidence of CC in women.

            USA

             

            • Sex: Women

            PA Assessment: Questionnaire / Phone interviews for the following variables, divided into 4 or 5 groups

              

            Prospective cohort

             

            • Age: 61.1 yr

             

            Multivariate RR (95% CI), TPA

             

            D & B score = 12

             

            • Characteristics: Free from cancer at baseline

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.45 (0.98-2.15)

             
                

               • G3 = 1.16 (0.77-1.75)

             
                

               • G4 = 1.27 (0.84-1.91)

             
                

               • G5 = 1.15 (0.76-1.75)

             
                

            p = 0.77

             
               

            TPA (MET h/d)

              
               

            G1 = 34.0-48.5

            Multivariate RR (95% CI), MPA

             
               

            G2 = 48.51-54.3

               • G1 = 1.00 (referent)

             
               

            G3 = 54.31-59.0

               • G2 = 1.23 (0.82-1.83)

             
               

            G4 = 59.1-64.9

               • G3 = 1.47 (0.99-2.21)

             
               

            G5 = 65.0-98.1

               • G4 = 0.94 (0.61-1.46)

             
                

               • G5 = 1.07 (0.70-1.62)

             
               

            MPA (h/d)

            p = 0.80

             
               

            G1 = 0-3.0

              
               

            G2 = 3.01-5.0

              
               

            G3 = 5.01-6.70

            Multivariate RR (95% CI), VPA

             
               

            G4 = 6.71-8.14

               • Q1 = 1.00 (referent)

             
               

            G5 = 8.15-18.0

               • Q2 = 1.19 (0.85-1.66)

             
                

               • Q3 = 0.87 (0.59-1.29)

             
               

            VPA (h/d)

               • Q4 = 1.10 (0.78-1.55)

             
               

            Q1 = 0

            p = 0.80

             
               

            Q2 = 0.1-1.0

              
               

            Q3 = 1.1-2.0

              
               

            Q4 = 2.1-14.0

              
               

            Outcome Measure: Incidence of CC

              
               

            Cox proportional HR

              

            Chao et al 2004 [276]

            To examine how the characteristics of recreational PA affect its association with colon cancer incidence among older.

            • n = 151,174 (70,403 men; 80,771 women)

            7 year follow up

            Number of cases: 940

            Increased amounts of time spent in recreational PA is associated with substantially lower risk of CC.

            USA

             

            • Sex: Men and women

            PA assessment: Questionnaire for the following variables

            Multivariate RR (95% CI) by recreational PA, men

             

            Prospective cohort

             

            • Age: mean 63 yr

             

               • G1 = 1.00 (referent)

             

            D & B score = 12

             

            • Cancer prevention study II Nutrition Cohort

             

               • G2 = 0.91 (0.69-1.19)

             
               

            Recreational PA (h/wk)

               • G3 = 0.72 (0.52-1.01)

             
               

            G1 = None

               • G4 = 0.86 (0.64-1.15)

             
               

            G2 = <2

               • G5 = 0.77 (0.54-1.08)

             
               

            G3 = 2-3

               • G6 = 0.58 (0.39- 0.87)

             
               

            G4 = 4-6

            p = 0.007

             
               

            G5 = 7

              
               

            G6 = ≥ 8

            Multivariate RR (95% CI) by recreational PA, women

             
               

            Recreational (MET h/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = None

               • G2 = 1.01 (0.70-1.44)

             
               

            G2 = <7, 7-13

               • G3 = 1.01 (0.68-1.49)

             
               

            G3 = 14-23

               • G4 = 0.97 (0.66-1.43)

             
               

            G4 = 24-29

               • G5 = 1.03 (0.65-1.65)

             
               

            G5 = ≥ 30

               • G6 = 0.65 (0.39-1.11)

             
                

            p = 0.14

             
               

            Walking (h/wk)

              
               

            Q1 = None

              
               

            Q2 = <4

            Multivariate RR (95% CI) by recreational PA, men and women

             
               

            Q3 = 4-6

               • G1 = 1.00 (referent)

             
               

            Q4 = ≥ 7

               • G2 = 0.94 (0.75-1.16)

             
                

               • G3 = 0.83 (0.65-1.07)

             
               

            Walking plus other

               • G4 = 0.89 (0.71-1.12)

             
               

            activities (h/wk)

               • G5 = 0.85 (0.64-1.12)

             
               

            Q1 = None

               • G6 = 0.60 (0.44-0.83)

             
               

            Q2 = <4

            p = 0.002

             
               

            Q3 = 4-6

              
               

            Q4 = ≥ 7

            Multivariate RR (95% CI) by MET h/wk men

             
               

            Outcome Measure: Incidence of CC

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.90 (0.68-1.18)

             
               

            Cox proportional HR

               • G3 = 0.83 (0.59-1.16)

             
                

               • G4 = 0.75 (0.55-1.01)

             
                

               • G5 = 0.86 (0.63-1.19)

             
                

               • G6 = 0.60 (0.41-0.87)

             
                

            p = 0.005

             
                

            Multivariate RR (95% CI) by MET h/wk women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.02 (0.71-1.46)

             
                

               • G3 = 0.98 (0.65-1.47)

             
                

               • G4 = 1.0 (0.68-1.47)

             
                

               • G5 = 0.94 (0.60-1.48)

             
                

               • G6 = 0.77 (0.48-1.24)

             
                

            p = 0.15

             
                

            Multivariate RR (95% CI) by MET h/wk men and women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.93 (0.75-1.16)

             
                

               • G3 = 0.88 (0.68-1.13)

             
                

               • G4 = 0.84 (0.66-1.06)

             
                

               • G5 = 0.89 (0.68-1.15)

             
                

               • G6 = 0.65 (0.49-0.87)

             
                

            p = 0.002

             
                

            Multivariate RR (95% CI) by walking, Men

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.87 (0.66-1.15)

             
                

               • Q3 = 0.83 (0.60-1.16)

             
                

               • Q4 = 0.88 (0.61-1.25)

             
                

            p = 0.34

             
                

            Multivariate RR (95% CI) by walking, women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.00 (0.70-1.44)

             
                

               • Q3 = 1.08 (0.71-1.63)

             
                

               • Q4 = 1.18 (0.71-1.95)

             
                

            p = 0.41

             
                

            Multivariate RR (95% CI) by walking plus other activities, men

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.73 (0.53-1.02)

             
                

               • Q3 = 0.85 (0.58-1.24)

             
                

               • Q4 = 0.53 (0.36-0.78)

             
                

            p = 0.02

             
                

            Multivariate RR (95% CI) by walking plus other activities, women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.99 (0.67-1.47)

             
                

               • Q3 = 0.72 (0.43-1.19)

             
                

               • Q4 = 0.59 (0.36-0.98)

             
                

            p = 0.07

             

            Colbert et al 2001 [277]

            To examine the association between OPA and LTPA and colon cancer in male smokers.

            • n = 29,133

            12 year follow-up

            Number of cases: 152

            OPA is protective against CC in a dose-response manner.

            USA

             

            • Sex: Men

               

            Prospective cohort

             

            • Age: 50-69 yr

            PA assessment: Interview for OPA and LTPA

            Multivariate RR (95% CI) by OPA

             

            D & B score = 13

             

            • Characteristics: Smokers

             

               • G1 = 0.61 (0.39-0.98)

             
              

            • Alpha- Tocopherol, Beta-Carotene Cancer Prevention Study

             

               • G2 = 1.00 (referent)

             
                

               • G3 = 0.60 (0.34-1.04)

             
               

            OPA

               • G4 = 0.45 (0.26-0.78)

             
               

            G1 = Non-worker

            p = 0.003

             
               

            G2 = Sedentary

              
               

            G3 = Light

            Multivariate RR (95% CI), by LTPA

             
               

            G4 = Moderate

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.82 (0.59-1.13)

             
               

            LTPA

              
               

            G1 = Sedentary

              
               

            G2 = Active

              
               

            Outcome Measure: incident CC

              
               

            Cox proportional HR

              

            Dosemeci et al 1993 [278]

            To examine associations between PA and cancer sites among workers in Turkey.

            • n = 6,236 (3,486 cases in men and 379 cases in women; 2,127 control men and 244 control women)

            PA assessment: Stanford Occupational Classification code system.

            Number of cases: 93

            Occupational EE is inversely related to risk of CC.

            Turkey

             

            • 93 cases for CC

             

            Multivariate OR (95% CI) by total occupational EE

             

            Case control

             

            • Sex: Men and women

             

               • G1 = 1.6 (0.9-2.8)

             
              

            • Age: not indicated

            Total Occupational EE (kj/min)

               • G2 = 1.1 (0.6-2.0)

             

            D & B score = 13

             

            • Characteristics: All hospitalized Cases: Diagnosed with CC. Controls: included subjects diagnosed as non-cancers and cancers which there is no suggestion of an association with PA.

            G1 = <8

               • G3 = 1.0 (referent)

             
               

            G2 = 8-12

            p = 0.04

             
               

            G3 = >12

            When adjusted for socioeconomic status p = 0.03

             
               

            Sitting time at work (h/d) Levels:

            Multivariate OR (95% CI) by sitting time at work

             
               

            G1 = <2

               • G1 = 1.00 (referent)

             
               

            G2 = 2-6

               • G2 = 1.5 (0.9-2.5)

             
               

            G3 = >6

               • G3 = 1.5 (0.8-3.0)

             
                

            p = 0.03

             
               

            Outcome Measure: Incident CC

            When adjusted for socioeconomic status p = 0.03

             
               

            Maximum likelihood estimates

              

            Friedenreich et al 2006 [279]

            To investigate the role of PA in the development of colon cancer.

            • n = 413,044

            4 year follow-up

            Multivariate RR (95% CI), TPA

            Inverse association between PA and risk of CC, particularly for right sided tumours.

              

            • Sex: Men and women

            PA assessment: modified Baecke Questionnaire

               • Q1 = 1.00 (referent)

             

            UK

             

            • Age: 35-70 yr

             

               • Q2 = 0.92 (0.76-1.12)

             
              

            • Characteristics: Free of cancer at baseline

             

               • Q3 = 0.86 (0.70-1.04)

             

            Prospective cohort

             

            • European Prospective Investigation into Nutrition and Cancer. (EPIC)

            TPA

               • Q4 = 0.78 (0.59-1.03)

             
               

            Q1 = Inactive

            p = 0.04

             

            D & B score = 14

              

            Q2 = Moderately inactive

            Multivariate RR (95% CI), TPA and right sided CC

             
               

            Q3 = Moderately active

               • Q1 = 1.00 (referent)

             
               

            Q4 = Active

               • Q2 = 1.79 (0.59-1.06)

             
               

            Household PA (MET-h/wk)

               • Q3 = 0.64 (0.47-0.86)

             
               

            Q1 = <19.5

               • Q4 = 0.65 (0.43-1.00)

             
               

            Q2 = 19.5-39.6

            p = 0.004

             
               

            Q3 = 39.6-73.9

              
               

            Q4 = ≥ 73.9

            Multivariate RR (95% CI), household PA and right sided CC

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.97 (0.75-1.27)

             
               

            Outcome Measure: Incident CC

               • Q3 = 0.84 (0.64-1.12)

             
                

               • Q4 = 0.74 (0.54-1.02)

             
                

            p = 0.05

             
               

            Cox proportional HR

              

            Giovannucci et al 1995 [280]

            To examine the association between PA and colon cancer.

            • n = 47,723

            6 year follow-up

            Multivariate RR (95% CI)

            A moderate level of PA was related to a substantially lower risk of CC in this cohort of middle age to elderly men.

              

            • Sex: Men

             

               • G1 = 1.00 (referent)

             
              

            • Age: 40-75 yr

            PA assessment: Questionnaire

               • G2 = 0.73 (0.48-1.10)

             

            USA

             

            • Characteristics: Health professionals

             

               • G3 = 0.94 (0.63-1.39)

             
                

               • G4 = 0.78 (0.51-1.20)

             

            Prospective cohort

             

            • Health Professionals Follow-up Study

            Outcome Measure: Incidence of colon cancer

               • G5 = 0.53 (0.32-0.88)

             
                

            p = 0.03

             

            D & B score = 12

                 
               

            Mantel-Haeszel estimator and logistic regression

              

            Isomura et al 2006 [281]

            To examine the relationship of OPA, LTPA, commuting, housework and shopping with colorectal cancer risk.

            • n = 1545 (778 cases, 767 controls)

            PA assessment: Questionnaire and interview for the following variables

               • Number of cases: 778

            Adds to the evidence that PA confers decreased risk of CC, especially of distal CC in both men and women.

            Japan

             

            • Sex: Men and women

             

            Multivariate OR (95% CI) for all CC by OPA, men

             
                

               • G1 = 1.00 (referent)

             

            Case control

             

            • Age: 20-74 yr

            OPA, men

               • G2 = 0.9 (0.6-1.4)

             
              

            • Characteristics: Free from cancer at baseline

            G1 = Sedentary

               • G3 = 0.7 (0.4-1.0)

             

            D & B score = 12

              

            G2 = Moderate

            p = 0.06

             
             

            .

             

            G3 = Hard

              
              

            • Fukuoka colorectal cancer study

             

            Multivariate OR (95% CI) for proximal

             
               

            OPA, women

            CC by OPA, men

             
               

            G1 = Sedentary

               • G1 = 1.00 (referent)

             
               

            G2 = Active

               • G2 = 1.2 (0.6-2.2)

             
                

               • G3 = 0.7 (0.4-1.4)

             
               

            Total non-OPA, men (MET-h/wk)

            p = 0.45

             
               

            G1 = 0.0

            Multivariate OR (95% CI) for distal CC by OPA, men

             
               

            G2 = 0.1-15.9

               • G1 = 1.00 (referent)

             
               

            G3 = 16.0

               • G2 = 0.8 (0.4-1.4)

             
                

               • G3 = 0.6 (0.4-1.0)

             
                

            p = 0.047

             
               

            Total non-OPA women (MET hr/wk)

              
               

            G1 = 0.0

              
               

            G2 = 0.1-15.9

              
               

            G3 = 16.0

            Multivariate OR (95% CI) for all CC by non-OPA, men

             
               

            Moderate or hard non-OPA, men (MET hr/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = 0.0

               • G2 = 0.9 (0.6-1.4)

             
               

            G2 = 0.1-14.9

               • G3 = 0.8 (0.5-1.2)

             
               

            G3 = ≥15.0

            p = 0.22

             
                

            Multivariate OR (95% CI) for proximal CC by non-OPA, men

             
               

            Moderate or hard non-OPA, women (MET hr/wk)

               • G1 = 1.00 (referent)

             
               

            G1 = 0.0

               • G2 = 1.2 (0.6-2.1)

             
               

            G2 = 0.1-14.9

               • G3 = 0.9 (0.5-1.7)

             
               

            G3 = 15.0

            p = 0.69

             
               

            Outcome Measure: Incident CC

            Multivariate OR (95% CI) for distal CC by non-OPA, men

             
                

               • G1 = 1.00 (referent)

             
               

            Multiple logistic regression analysis

               • G2 = 0.8 (0.5-1.3)

             
                

               • G3 = 0.7 (0.4-1.1)

             
                

            p = 0.19

             
                

            Multivariate OR (95% CI) for all CC by non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.9 (0.5-1.5)

             
                

               • G3 = 0.8 (0.5-1.4)

             
                

            p = 0.45

             
                

            Multivariate OR (95% CI) for proximal CC by non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.5 (0.7-3.3)

             
                

               • G3 = 1.6 (0.7-3.6)

             
                

            p = 0.41

             
                

            Multivariate OR (95% CI) for distal CC by non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.7 (0.4-1.3)

             
                

               • G3 = 0.6 (0.3-1.1)

             
                

            p = 0.12

             
                

            Multivariate OR (95% CI) for all CC by moderate or hard non-OPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.8 (0.6-1.2)

             
                

               • G3 = 0.8 (0.5-1.1)

             
                

            p = 0.24

             
                

            Multivariate OR (95% CI) for proximal CC by moderate or hard non-OPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.1 (0.6-2.1)

             
                

               • G3 = 1.0 (0.6-1.8)

             
                

            p = 0.99

             
                

            Multivariate OR (95% CI) for distal CC by moderate or hard non-OPA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.7 (0.4-1.1)

             
                

               • G3 = 0.7 (0.4-1.0)

             
                

            p = 0.12

             
                

            Multivariate OR (95% CI) for all CC by moderate or hard non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.0 (0.6-1.6),

             
                

               • G3 = 0.8 (0.5-1.4)

             
                

            p = 0.35

             
                

            Multivariate OR (95% CI) for proximal CC by moderate or hard non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.3 (0.6-2.5)

             
                

               • G3 = 1.3 (0.6-2.7)

             
                

            p = 0.59

             
                

            Multivariate OR (95% CI) for distal CC by moderate or hard non-OPA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.8 (0.5-1.5)

             
                

               • G3 = 0.5 (0.3-1.1)

             
                

            p = 0.41

             

            Johnsen at el 2006 [282]

            To investigate the effects of OPA on colon cancer incidence.

            • n = 54,478 (28,356 men, 26,122 women)

            7.6 year follow-up

               • Number of cases: 140 women, 157 men

            No support for the hypothesis that OPA measured by MET-score may be associated with a lower risk of CC.

              

            • Sex: Men and women

            PA assessment: Questionnaire for OPA by MET score, 4 groups

               • Number of dropouts: <0.8%

             

            Denmark

             

            • Age: 50-64 yr

             

            Multivariate RR (95% CI), men

             

            Prospective cohort

             

            • Characteristics: Free of Cancer at baseline

            Q1 = Sitting

               • Q1 = 1.00 (referent)

             
              

            • Diet, Cancer and Health Study

            Q2 = Standing

               • Q2 = 1.11 (0.69-1.77)

             
               

            Q3 = Manual

               • Q3 = 1.17 (0.77-1.79)

             

            D & B score = 13

              

            Q4 = Not working

               • Q4 = 0.95 (0.58-1.55)

             
               

            Outcome Measure: Incidence of colon cancer

            Multivariate RR (95% CI), women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.15 (0.68-1.93)

             
                

               • Q3 = 1.34 (0.83-2.16)

             
               

            Cox proportional HR

               • Q4 = 0.96 (0.60-1.53)

             

            Larsen et al 2006 [283]

            To examine the relationship between PA and colorectal cancer.

            • n = 6,961

            PA assessment: Questionnaire (scored from 2-12), divided into quartiles:

            Number of cases: 108

            Inactivity was not a significant risk factor for advanced colonic neoplasia.

              

            • Sex: Men and women

             

            RR (95% CI)

             

            Norway

             

            • Age: 50-64

             

               • Q1 = 1.00 (referent)

             
              

            • Characteristics: No history of colorectal surgery, radiotherapy, cardiopulmonary disease, anticoagulant therapy, coronary episode.

            Q1 = 2-4

               • Q2 = 0.61 (0.32-1.16)

             

            Cross-sectional evaluation within a randomized controlled trial

              

            Q2 = 5

               • Q3 = 0.75 (0.45-1.26)

             
               

            Q3 = 6

               • Q4 = 0.56 (0.34-0.92)

             
               

            Q4 = 7-12

            p = 0.04

             
               

            Outcome Measure: Positive test for colonic neoplasia

            Multivariate RR (95% CI)

             

            D & B score = 13

               

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.64 (0.33-1.25)

             
                

               • Q3 = 0.82 (0.47-1.43)

             
               

            Multivariate logistic regression analysis

               • Q4 = 0.67 (0.39-1.16)

             
                

            p = 0.23

             

            Larsson et al 2006 [284]

            To investigate the association between PA and colorectal cancer.

            • n = 45,906

            7.1 year follow-up

            Number of cases: 309 (133 proximal, 138 distal)

            Results support a role of PA in reducing the risk of CC.

              

            • Sex: Men

               
              

            • Age: 45-79 yr

            PA assessment: Questionnaire for the following variables

              

            Sweden

             

            • Characteristics: Free of cancer at baseline

             

            Multivariate HR (95% CI) by LTPA

             
                

               • Q1 = 1.00 (referent)

             

            Prospective cohort

               

               • Q2 = 0.66 (0.43-1.02)

             
               

            LTPA (min/day)

               • Q3 = 0.68 (0.46-1.01)

             
               

            Q1 = <10

               • Q4 = 0.56 (0.37-0.83)

             

            D & B score = 14

              

            Q2 = 10-29

            p = 0.01

             
               

            Q3 = 30-59

              
               

            Q4 = ≥ 60

            Multivariate HR (95% CI) by home/housework PA

             
               

            Home/housework PA (h/day)

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.75 (0.58-0.97)

             
               

            Q1 = none

               • Q3 = 0.75 (0.58-0.97)

             
               

            Q2 = <1

               • Q4 = 0.68 (0.48-0.96)

             
               

            Q3 = 1-2

            p = 0.01

             
               

            Q4 = ≥ 3

              
               

            Incidence of Proximal CC(h/day)

            Multivariate HR (95% CI) for distal CC by LTPA

             
               

            G1 = <1

               • Q1 = 1.00 (referent)

             
               

            G2 = 1-2

              
               

            G3 = ≥ 3

               • Q2 = 0.51 (0.28-0.93)

             
                

               • Q3 = 0.50 (0.29-0.87)

             
                

               • Q4 = 0.40 (0.22-0.70)

             
                

            p = 0.01

             
               

            Outcome Measure: Incident CC

              
                

            Multivariate HR (95% CI) for proximal CC by home/housework PA

             
               

            Cox proportional HR

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.78 (0.53-1.14)

             
                

               • G3 = 0.50 (0.29-0.89)

             
                

            p = 0.02

             

            Lee and Paffenbarger 1994 [285]

            To predict cancer risk using prospective assessments of PA.

            • n = 17,607

            26 year follow-up

            • Number of cases: 280

            Found a trend, of borderline statistical significance toward decreasing CC risk with increasing PA.

              

            • Sex: Men

             

            • Number of dropouts: 14%

             
              

            • Age: 30-79 yr

            PA assessment: Questionnaire for PA level (kcal/wk)

              

            USA

             

            • Characteristics: Healthy at baseline

             

            Multivariate RR (95% CI), Model A: PA in 1962/1966 and updated in 1977

             
              

            • Harvard College Alumni

             

               • G1 = 1.00 (referent)

             

            Prospective cohort

              

            G1 = <1000

               • G2 = 1.07 (0.81-1.42)

             
               

            G2 = 1000-2499

               • G3 = 1.08 (0.81-1.46)

             
               

            G3 = ≥ 2500

            p = 0.58

             

            D & B score = 13

                 
               

            Outcome Measure: Incidence of fatal and non fatal CC

            Multivariate RR (95% CI), Model B: PA in both 1962/1966 and 1977

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.75 (0.42-1.35)

             
               

            Cox proportional HR

               • G3 = 0.94 (0.54-1.64)

             
                

            p = 0.76

             

            Lee et al 1997 [286]

            To investigate whether PA alters the risk of developing CC in men.

            • n = 20,614

            10.9 year follow-up

            Number of cases: 217

            Data does not support the hypothesis that PA is related inversely to risk of developing CC.

              

            • Sex: Men

               
              

            • Age: 40-84 yrs

            PA assessment: Questionnaire for the following variables

            Multivariate RR (95% CI), frequency of

             

            USA

             

            • Characteristics: Physicians, free of cancer at baseline

             

            PA at baseline

             
                

               • G1 = 1.00 (referent)

             

            Prospective cohort

               

               • G2 = 1.1 (0.7-1.7)

             
               

            Frequency of PA at baseline (times/week)

               • G3 = 1.2 (0.8-1.6)

             
              

            Physicians Health Study

             

               • G4 = 1.1 (0.7-1.6)

             

            D & B score = 15

              

            G1 = <1

            p = 0.6

             
               

            G2 = 1

              
               

            G3 = 2-4

            RR (95% CI), frequency of PA at baseline and 36 months

             
               

            G4 = 5+

              
                

               • G1 = 1.00 (referent)

             
               

            Frequency of PA at baseline and 36 months

               • G2 = 1.2 (0.5-2.7)

             
               

            G1 = 1/<1

               • G3 = 1.4 (0.9-2.3)

             
               

            G2 = <1/1+

               • G4 = 1.3 (0.9-2.0)

             
               

            G3 = 1+/< 1

              
               

            G4 = 1+/1+

              
               

            Outcome Measure: Incidence of fatal and non-fatal CC

              
               

            Cox proportional HR

              

            Lee et al 2007 [287]

            To examine the association between PA and the risk of developing CRC in Japanese men and women.

            • n = 65,022

            6 year follow-up

            Number of cases: 154 proximal CC, 166 distal CC

            PA may prevent CC among Japanese men.

              

            • Sex: Men and women

               

            Japan

             

            • Age: 40-69 yr

             

            Multivariate RR (95% CI) for CC men

             
              

            • Characteristics

            PA assessment: Questionnaire for PA level (median MET hr/d)

               • Q1 = 1.00 (referent)

             

            Prospective cohort

             

            • Ethnicity: Japanese

            Q1 = 28.25

               • Q2 = 0.87 (0.61-1.26)

             
               

            Q2 = 33.25

               • Q3 = 0.62 (0.41-0.95)

             
               

            Q3 = 35.25

               • Q4 = 0.58 (0.39-0.87)

             

            D & B score = 13

              

            Q4 = 43.75

            p = 0.006

             
               

            Outcome Measure: Incidence of CC

            Multivariate RR (95% CI) for proximal CC men

             
               

            Cox proportional HR

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.89 (0.52-1.51)

             
                

               • Q3 = 0.44 (0.22-0.86)

             
                

               • Q4 = 0.29 (0.14-0.60)

             
                

            p < 0.001

             
                

            Multivariate RR (95% CI) for distal CC Men

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 0.92 (0.54-1.54)

             
                

               • Q3 = 0.75 (0.42-1.33)

             
                

               • Q4 = 0.89 (0.53-1.51)

             
                

            p = 0.685

             
                

            PA level and incidence of CC women

             
                

            Total CC

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.03 (0.65-1.64)

             
                

               • Q3 = 0.91 (0.57-1.47)

             
                

               • Q4 = 0.89 (0.54-1.49)

             
                

            p = 0.610

             
                

            Proximal CC women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.14 (0.61-2.12)

             
                

               • Q3 = 1.01 (0.53-1.89)

             
                

               • Q4 = 0.55 (0.24-1.26)

             
                

            p = 0.151

             
                

            Distal CC women

             
                

               • Q1 = 1.00 (referent)

             
                

               • Q2 = 1.09 (0.52-2.29)

             
                

               • Q3 = 0.77 (0.34-1.74)

             
                

               • Q4 = 1.37 (0.66-2.85)

             
                

            p = 0.401

             

            Longnecker et al 1995 [288]

            To examine the relationship between OPA and vigorous LTPA and the risk of cancer of the right colon and rectum.

            • n = 242 rectal cancer and 703 controls

            PA assessment: Interview for vigorous LTPA and OPA (coded and self-reported), divided into groups:

            Number of cases: 163

            The amount of time spent at vigorous LTPA was associated with a decreased risk of cancer of the right colon.

              

            • Sex: Men

             

            RR (95% CI) by vigorous LTPA

             

            USA

             

            • Age: ≥ 31 yr

             

               • G1 = 1.00 (referent)

             
              

            • Characteristics: Case: Diagnosed with adenocarcinoma of the right colon or rectum. Controls: Both community and hospital. No history of large bowel cancer.

             

               • G2 = 0.73 (0.23-2.29)

             

            Case control

               

               • G3 = 0.47 (0.16-1.36)

             
               

            Vigorous LTPA (h/wk)

               • G4 = 0.60 (0.35-1.00)

             

            D & B score = 14

              

            G1 = 0

            p = 0.03

             
               

            G2 = ≤ 0.5

              
               

            G3 = 1

            Multivariate OR (95% CI) by vigorous

             
               

            G4 = >1

            LTPA

             
                

               • G1 = 1.00 (referent)

             
               

            Coded lifetime OPA

               • G2 = 0.81 (0.26-2.54)

             
               

            G1 = Sedentary

               • G3 = 0.36 (0.11-1.14)

             
               

            G2 = light work

               • G4 = 0.57 (0.33-0.97)

             
               

            G3 = moderate

            p = 0.06

             
               

            G4 = heavy

              
               

            Self reported lifetime

            Multivariate OR (95% CI) by coded lifetime OPA

             
               

            OPA

              
               

            G1 = Sedentary

               • G1 = 1.00 (referent)

             
               

            G2 = light work

               • G2 = 0.79 (0.39-1.61)

             
               

            G3 = more than light work

               • G3 = 0.79 (0.36-1.74)

             
                

               • G4 = 0.99 (0.30-3.22)

             
                

            p = 0.42

             
               

            Outcome Measure: Diagnosed with CC

              
                

            Multivariate OR (95% CI) by self reported lifetime OPA

             
               

            Conditional Logistic Regression

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.85 (0.41-1.76)

             
                

               • G3 = 0.68 (0.31-1.52)

             
                

            p = 0.15

             

            Mai et al 2007 [289]

            To examine in detail the relationship between recreational PA and invasive CC among women.

            • n = 120,147

            7 year follow-up

            Number of cases: 395

            Modest inverse association between recreational PA and CC.

              

            • Sex: Women

               
              

            • Age: 22-84 yr

            PA assessment: Questionnaire

            RR (95% CI) by MPA over past 3 years

             

            USA

             

            • Characteristics: no prior history of CC

             

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.95 (0.72-1.24)

             

            Prospective cohort

              

            MPA over past 3 yrs (h/wk/yr)

               • G3 = 0.78 (0.62-0.97)

             
              

            • California Teachers Study

             

            p = 0.02

             
               

            G1 = 0-0.50

              

            D & B score = 15

              

            G2 = 0.51-1.99

            RR (95% CI) by strenuous + moderate (lifetime) PA:

             
               

            G3 = ≥ 2.00

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.79 (0.56-1.11)

             
               

            Strenuous + Moderate (lifetime) PA (h/wk/yr)

               • G3 = 0.64 (0.44-0.93)

             
                

            p = 0.04

             
               

            G1 = 0.0-0.50

              
               

            G2 = 0.51-3.99

              
               

            G3 = ≥ 4.00

              
               

            Outcome Measure: Incidence of invasive adenocarcinoma of the colon

              
               

            Cox proportional HR

              

            Martinez et al 1997 [290]

            To examine whether LTPA could significantly influence the risk of CC in women.

            • n = 89,448

            6 year follow-up

            Number of cases: 212

            Significant inverse association between LTPA and incidence of CC in women.

              

            • Sex: Women

               
              

            • Age: 30-55 yr

            PA assessment: Questionnaire for LTPA

            Multivariate RR (95% CI) for all CC

             

            USA

             

            • Characteristics: Nurses, free from cancer at baseline

             

               • G1 = 1.00 (referent)

             
               

            G1 = <2

               • G2 = 0.71 (0.44-1.15)

             

            Prospective

              

            G2 = 2-4

               • G3 = 0.78 (0.50-1.20)

             

            cohort

              

            G3 = 5-10

               • G4 = 0.67 (0.42-1.07)

             
               

            G4 = 11-21

               • G5 = 0.54 (0.33-0.90)

             

            D & B score = 14

              

            G5 = >21

            p = 0.03

             
               

            Outcome Measure: Incidence of CC

            Multivariate RR (95% CI) for distal CC

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.92 (0.48-1.79)

             
               

            Mantel-Haenszel Estimator and logistic regression models

               • G3 = 0.81 (0.43-1.55)

             
                

               • G4 = 0.71 (0.36-1.41)

             
                

               • G5 = 0.31 (0.12-0.77)

             
                

            p = 0.01

             
                

            Multivariate RR (95% CI) for proximal

             
                

            CC

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.54 (0.23-1.22)

             
                

               • G3 = 0.79 (0.40-1.56)

             
                

               • G4 = 0.62 (0.30-1.32)

             
                

               • G5 = 0.77 (0.38-1.58)

             
                

            p = 0.67

             

            Nilsen et al 2008 [291]

            To study the separate associations of recreational PA with the incidence of, and mortality from cancer in the ascending, transverse, descending and sigmoid segments of the colon.

            • n = 59,369

            17 year follow-up

            Number of cases: 736

            Strong inverse associations between recreational PA and risk of cancer morbidity and mortality of the transverse and sigmoid colon but no association for cancer in the ascending and descending colon.

              

            • Sex: Men and women

            PA assessment: Questionnaire for frequency and duration of recreational PA

            HR (95% CI) by frequency of recreational PA, men

             

            Norway

             

            • Age: not indicated

             

               • G1 = 1.00 (referent)

             

            Prospective cohort

             

            • Characteristics: Free from cancer at baseline

             

               • G2 = 0.84 (0.60-1.19)

             
              

            • Nord-Trondelag Health Study

             

               • G3 = 0.82 (0.58-1.17)

             
                

               • G4 = 0.81 (0.57-1.15)

             

            D & B score = 14

              

            Frequency of Recreational PA (times per week)

               • G5 = 0.77 (0.54-1.09)

             
               

            G1 = none

            p = 0.18

             
               

            G2 = <1

            HR (95% CI) by frequency of

             
               

            G3 = 1

            recreational PA, women

             
               

            G4 = 2-3

               • G1 = 1.00 (referent)

             
               

            G5 = ≥ 4

               • G2 = 0.91 (0.66-1.25)

             
                

               • G3 = 0.79 (0.57-1.09)

             
               

            Duration of recreational PA (min per exercise)

               • G4 = 0.66 (0.47-0.92)

             
                

               • G5 = 0.99 (0.72-1.36)

             
               

            G1 = none

            p = 0.35

             
               

            G2 = <15

              
               

            G3 = 15-30

            HR (95% CI) by duration of recreational

             
               

            G4 = 31-60

            PA, men

             
               

            G5 = >60

               • G1 = 1.00 (referent)

             
                

               • G2 = 1.07 (0.71-1.60)

             
               

            Intensity of recreational PA

               • G3 = 0.80 (0.57-1.12)

             
                

               • G4 = 0.68 (0.48-0.97)

             
               

            G1 = none

               • G5 = 0.74 (0.50-1.08)

             
               

            G2 = Low

            p = 0.02

             
               

            G3 = Moderate/High

            HR (95% CI) by duration of recreational PA, women

             
               

            Summary score for recreational PA

               • G1 = 1.00 (referent)

             
               

            G1 = None

               • G2 = 0.85 (0.59-1.23)

             
               

            G2 = Low

               • G3 = 0.81 (0.60-1.09)

             
               

            G3 = High

               • G4 = 0.73 (0.53-1.01)

             
               

            By subsite-specific (transverse colon, decending colon, sigmoid colon) CC

               • G5 = 0.84 (0.53-1.34)

             
                

            p = 0.10

             
                

            HR (95% CI) by intensity of recreational PA, men

             
               

            Levels of REC PA:

              
               

            G1 = None

               • G1 = 1.00 (referent)

             
               

            G2 = < 1 x/wk

               • G2 = 0.83 (0.62-1.12)

             
               

            G3 = low score

               • G3 = 0.74 (0.52-1.06)

             
               

            G4 = high score

            p = 0.11

             
               

            Outcome Measure: incidence of fatal and non fatal CC

            HR (95% CI) by intensity of recreational PA, women

             
               

            Cox proportional HR

              
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.77 (0.59-1.01)

             
                

               • G3 = 0.89 (0.60-1.32)

             
                

            p = 0.33

             
                

            HR (95% CI) by summary score for recreational PA, men

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.85 (0.62-1.16)

             
                

               • G3 = 0.69 (0.48-0.98)

             
                

            p = 0.06

             
                

            HR (95% CI) by summary score for recreational PA, women

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.86 (0.64-1.01)

             
                

               • G3 = 0.72 (0.53-0.98)

             
                

            p = 0.03

             
                

            HR (95% CI) by total CC and recreational PA, incidence

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.88 (0.70-1.12)

             
                

               • G3 = 0.87 (0.70-*1.08)

             
                

               • G4 = 0.73 (0.58-0.92)

             
                

            p = 0.009

             
                

            HR (95% CI) by subsite specific CC and recreational PA, death

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.87 (0.64-1.18)

             
                

               • G3 = 0.79 (0.59-1.04)

             
                

               • G4 = 0.56 (0.41-0.78)

             
                

            p <0.001

             
                

            HR (95% CI) for transverse CC incidence and recreational PA

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.75 (0.44-1.28)

             
                

               • G3 = 0.66 (0.41-1.08)

             
                

               • G4 = 0.44 (0.25-0.78)

             
                

            p = 0.004

             
                

            HR (95% CI) for transverse CC death and recreational PA

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.73 (0.36-1.49)

             
                

               • G3 = 0.40 (0.19-0.82)

             
                

               • G4 = 0.33 (0.14-0.76)

             
                

            p = 0.002

             
                

            HR (95% CI) for sigmoid CC incidence and recreational PA

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.88 (0.59-1.32)

             
                

               • G3 = 0.68 (0.46-1.01)

             
                

               • G4 = 0.48 (0.31-0.75)

             
                

            p <0.001

             
                

            HR (95% CI) for sigmoid CC death and recreational PA

             
                

               • G1 = 1.00 (referent)

             
                

               • G2 = 0.78 (0.45-1.35)

             
                

               • G3 = 0.51 (0.30-0.87)

             
                

               • G4 = 0.29 (0.15-0.56)

             
                

            p <0.001

             

            Schnohr et al 2005 [292]

            To assess the association between LTPA and incidence of cancer in the general population.

            • n = 28,259 (15,043 men,13,216 women)

            14 year follow-up

               • Number of cases: 215 men, 108 women

            For the most active men, VPA was associated with a non-significant lower risk of CC.

            Denmark

              

            PA assessment: Questionnaire for LTPA

            Multivariate RR (95% CI), men

             
              

            • Sex: Men and women

            G1 = Low

               • G1 = 1.00 (referent)

             

            Prospective cohort

              

            G2 = Moderate

               • G2 = 1.08 (0.74-1.57)

             
              

            • Age: 20-93 yr

            G3 = Vigorous

               • G3 = 0.72 (0.47-1.11)

             

            D & B score = 13

             

            • Characteristics: Free from cancer at baseline

            Outcome Measure: Incidence of CC

            p =0.06

             
                

            Multivariate RR (95% CI), women

             
              

            • Copenhagen Heart Study, The Copenhagen County Centre of Preventive Medicine and the Copenhagen M