Leisure Time, Occupational, and Commuting Physical Activity and the Risk of Stroke

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1 Leisure Time, Occupational, and Commuting Physical Activity and the Risk of Stroke Gang Hu, PhD; Cinzia Sarti, PhD; Pekka Jousilahti, PhD; Karri Silventoinen, PhD; Noël C. Barengo, MD; Jaakko Tuomilehto, PhD Background and Purpose The role of physical activity, especially that of occupational and commuting physical activity, in the prediction of stroke risk is not properly established. We assessed the relationship of different types of physical activity with total and type-specific stroke risk. Methods We prospectively followed Finnish subjects 25 to 64 years of age without a history of coronary heart disease, stroke, or cancer at baseline. Hazard ratios (HRs) for incident stroke were estimated for different levels of leisure time, occupational, and commuting physical activity. Results During a mean follow-up of 19.0 years, 2863 incident stroke events were ascertained. The multivariate-adjusted (age, sex, area, study year, body mass index, systolic blood pressure, cholesterol, education, smoking, alcohol consumption, diabetes, and other 2 types of physical activity) HRs associated with low, moderate, and high leisure time physical activity were 1.00, 0.86, and 0.74 (P trend 0.001) for total stroke, 1.00, 0.87, and 0.46 (P trend 0.011) for subarachnoid hemorrhage, 1.00, 0.77, and 0.63 (P trend 0.024) for intracerebral hemorrhage, and 1.00, 0.87, and 0.80 (P trend 0.001) for ischemic stroke, respectively. The multivariate-adjusted HRs associated with none, 1 to 29, and 30 minutes of active commuting were 1.00, 0.92, and 0.89 (P trend 0.043) for total stroke, and 1.00, 0.93, and 0.86 (P trend 0.028) for ischemic stroke, respectively. had a modest association with ischemic stroke in the multivariate analysis (P trend 0.046). Conclusion A high level of leisure time physical activity reduces the risk of all subtypes of stroke. Daily active commuting also reduces the risk of ischemic stroke. (Stroke. 2005;36: ) Key Words: exercise incidence stroke There is good evidence that regular physical activity reduces the risk for cardiovascular disease. 1 However, the protective effect of physical activity on stroke risk is less clear, and the results are inconsistent. Several studies have found an inverse association between regular physical activity and the risk of stroke, 2 7 whereas others have indicated a U-shaped association or no association In addition, it is not clear whether other types of physical activities, such as occupational and daily commuting physical activity on foot or by bicycle, are independently related to the risk of stroke. These studies have focused on total stroke risk, and few studies have assessed the association between physical activity and different subtypes of stroke. 3,7,11 A recent meta-analysis comprising 23 studies indicated that a high level of physical activity is associated with a reduced risk of total, ischemic, and hemorrhagic strokes. 13 The aim of this study is to assess whether leisure time, occupational, or commuting physical activity is independently associated with a reduced risk of total and different types of stroke. Methods Subjects Between 1972 and 1997, every 5 years, 6 independent population surveys were performed in 5 geographic areas of Finland among the population 25 to 64 years of age. The sampling methods have been described previously in detail. 14 The total sample size of the 6 surveys was The participation rate varied by year from 74% to 88%. 14 After excluding 2002 subjects with a history of coronary heart disease, stroke, or cancer at baseline, and 2335 with incomplete data on any required variables, the present analyses include men and women. These surveys were conducted according to the ethical rules of the National Public Health Institute, and the investigations were performed in accordance with the Declaration of Helsinki. Baseline Measurements A self-administered questionnaire was mailed to participants including questions about smoking, alcohol consumption, socioeconomic factors, medical history, and physical activity: leisure time, occupational, and commuting physical activity. Details have been presented previously, and these questions were similar to those used and validated in the Seven Countries Study. 23 In addition, physical activity has been successfully used previously, showing a high Received February 9, 2005; final revision received June 2, 2005; accepted June 19, From the Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland (G.H., C.S., P.J., J.T.); Department of Public Health, University of Helsinki, Finland (G.H., C.S., P.J., K.S., J.T.); Department of Public Health and General Practice, University of Kuopio, Finland (N.C.B.); and South Ostrobothnia Central Hospital, Seinäjoki, Finland (J.T.). Correspondence to Gang Hu, MD, PhD, Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166, FIN Helsinki, Finland. hu.gang@ktl.fi 2005 American Heart Association, Inc. Stroke is available at DOI: /01.STR c 1994

2 Hu et al Different Types of Physical Activity and Stroke Risk 1995 correlation with physical fitness, as measured by maximal oxygen uptake. 24 Self-reported leisure time physical activity was classified into 3 categories: (1) low (almost completely inactive, eg, reading, watching television, or doing some minor physical activity that was not of a moderate or high level), (2) moderate (some physical activity for 4 hours per week, eg, walking, cycling, light gardening, but excluding travel to work), and (3) high (vigorous physical activity for 3 hours per week, eg, running, jogging, swimming, heavy gardening, or regular exercise or competitive sports several times per week). Occupational physical activity was classified as: (1) light (physically very easy, sitting office work, eg, secretary), (2) moderate (standing and walking, eg, store assistant, light industrial worker), and (3) active (walking and lifting, or heavy manual labor, eg, industrial or farm work). The daily commuting return journey was categorized into 3 categories: (1) using motorized transportation or no work (0 minutes of walking or cycling), (2) walking or bicycling 1 to 29 minutes, and (3) walking or bicycling for 30 minutes. Measurements of height, weight, systolic blood pressure (SBP), and serum total cholesterol were made at baseline examination using a standardized protocol. 14 Prospective Follow-Up The study cohorts were followed until the end of 2003 through computerized register linkage by identification numbers. Mortality data were obtained from Statistics Finland and data on nonfatal events from the National Hospital Discharge Register. The Eighth, Ninth, and Tenth Revisions of the International Classification of Diseases (ICD) were used to identify subarachnoid hemorrhage (430 and I60), intracerebral hemorrhage (431 and I61 I62), intracerebral infarction (432 to 438 and I63 I66), and any stroke (430 to 438 and I60 I66) events. ICD-9 code 432 was classified as an intracerebral hemorrhage. Stroke events that occurred before the baseline survey were identified from the Hospital Discharge Register and excluded from the analyses. The validity of the diagnosis of acute stroke in Finland is good for hospital discharge register (agreement in 90%) and death register (agreement in 97%). 25 End points during follow-up were incident stroke events, defined as either the first nonfatal stroke event or stroke death without a preceding nonfatal event. Altogether, we identified cerebrovascular 2863 events (260 subarachnoid hemorrhage, 339 intracerebral hemorrhage, and 2264 ischemic) during a mean follow-up of 19.0 years. Statistical Analyses Independent samples t tests and 2 tests were used to compare the mean levels of continuous variables and the prevalence of categorical variables between subjects with and without incident stroke. We assessed correlations of any 2 types of physical activity through partial correlation coefficients and estimated the association of physical activity with stroke risk by Cox proportional hazard models. Physical activity categories were included in the models as dummy and categorical variables, and the significance of the trend over different categories of physical activity was tested in the same models by giving an ordinal numeric value for each dummy variable. The proportional hazards assumption in the Cox model was assessed with graphical methods and with models including time-by-covariate interactions (time-dependent, all types of physical activity). 26 In general, all proportionality assumptions were appropriate across different types of stroke with different types of physical activity. The analyses were first performed adjusting for age, area, and study year, and further for education (tertiles), body mass index (BMI), SBP, total cholesterol, smoking (never, past, and current), alcohol consumption (yes/no), history of diabetes (yes/no), and the other 2 types of physical activity. Because the interactions between sex and each type of physical activity on stroke risk were not statistically significant, data for men and women were combined in some analyses. Results General characteristics of the study population at baseline are presented in Table 1. Age-, sex-, area-, and study year adjusted correlations were 0.19 for occupational and commuting physical activity (P 0.001), 0.03 for occupational and leisure time physical activity (P 0.001), and 0.07 for commuting and leisure time physical activity (P 0.001). Leisure Time Physical Activity and the Risk of Stroke Age-, area-, and study year adjusted hazard ratios (HRs) of stroke incidence associated with low, moderate, and high leisure time physical activity were 1.00, 0.80, and 0.59 (P trend 0.001) in men, 1.00, 0.82, and 0.67 (P trend 0.001) in women, and 1.00, 0.81, and 0.62 (P trend 0.001) in men and women combined (adjusted also for sex), respectively (Table 2). Further adjustment for other risk factors (education, BMI, SBP, cholesterol, smoking, alcohol consumption, and diabetes) and even for occupational and commuting physical activity affected the results only slightly (all P trend 0.05). Occupational Activity and the Risk of Stroke There was a nonsignificant inverse association between occupational activity and the stroke risk in men and women. In both sexes combined, the inverse association was significant after adjustment for age, sex, area, study year, and other risk factors (the HRs associated with light, moderate, and active occupational activity were 1.00, 0.90, and 0.87, respectively; P trend 0.007) but no longer after additional adjustment for leisure time and commuting physical activity (P trend 0.060). When moderate and active occupational activity were combined, the HR at moderate/active occupational activity versus light occupational activity was 0.91 (95% CI, 0.84 to 0.99; P 0.027) after adjustment for all confounding factors, including leisure time and commuting physical activity. Commuting Physical Activity and the Risk of Stroke Daily commuting physical activity on foot or by bicycle was modestly and inversely associated with the risk of stroke among men (P trend 0.047) and women (P trend 0.018) after adjustment for age, area, study year, and other risk factors. In both sexes combined, the inverse association remained modest after adjustment for sex, other risk factors, leisure time, and occupational physical activity (the HRs associated with none, 1 to 29, and 30 minutes of active commuting were 1.00, 0.92, and 0.89, respectively; P trend 0.043). All Three Types of Physical Activity and the Risk of Stroke In the multivariate analyses, we estimated joint effects of all 3 types of physical activity on stroke risk (Table 3). We dichotomized all 3 types of physical activity at low/light versus moderate to high/active levels for leisure time and occupational physical activity and for commuting physical activity (any versus none). Compared with the subjects who reported low levels of leisure time, occupational, and commuting physical activity, the participants who reported 2 or 3 types of moderate to high physical activity had a 21% to 31% decreased risk of stroke, and the participants who reported only 1 of 3 types of moderate to high physical activity had a 14% to 21% decreased risk of stroke. Physical Activity and the Risk of Stroke Subtypes After adjustment for age, sex, other risk factors, and occupational and commuting physical activity, the HRs associated with low, moderate, and high leisure time physical activity were 1.00, 0.87, and 0.46 (P trend 0.011) for subarachnoid hemorrhage, 1.00, 0.77, and 0.63 (P trend 0.024) for intrace-

3 1996 Stroke September 2005 TABLE 1. General Characteristics of Study Subjects at Baseline According to the Stroke Outcome During the Follow-Up* Men Women Nonstroke Stroke Nonstroke Stroke (n ) (n 1497) P Value (n ) (n 1366) P Value Age, y BMI, kg/m SBP, mm Hg Total cholesterol, mg/dl Education, % Tertile Tertile Tertile Alcohol drinker, % Current smoker, % Diabetes, % Leisure time physical activity, % Low Moderate High , % Light Moderate Active Walking or cycling to/from work, % min/day min/day min/day *Characteristics are defined at baseline examination (see Methods); t test for continuous variables and 2 test for categorical variables. rebral hemorrhage, and 1.00, 0.87, and 0.80 (P trend 0.001) for ischemic stroke, respectively (Table 4). Modest associations between occupational activity and ischemic stroke (P trend 0.046) and between commuting physical activity and ischemic stroke (P trend 0.028) were found in the multivariate analyses. When we used nonfatal stroke events as outcome, these inverse associations between leisure time physical activity and each type of subarachnoid hemorrhagic, intracerebral hemorrhagic, and ischemic stroke, modest associations between occupational activity and ischemic stroke, and between commuting physical activity and ischemic stroke did not appreciably change (data not shown). Discussion A high level of leisure time physical activity reduced the risk for total and different subtypes of stroke incidence, including subarachnoid hemorrhagic, intracerebral hemorrhagic, and ischemic strokes. Moderate level of leisure time physical activity reduced the risk for intracerebral hemorrhagic and ischemic strokes. Daily commuting physical activity on foot or by bicycle reduced the risk of ischemic stroke. A simultaneous engagement in 2 or 3 types of physical activity showed a slightly stronger protective effect than having only 1 type of activity. The findings from the previous prospective studies on the association between leisure time physical activity and stroke risk are inconsistent. Some studies, 2 7 but not all, 9 12 have indicated a significant inverse association between leisure time physical activity and stroke risk. Moreover, studies on women are sparse, 4 7,12 and only 3 of them have found a significant inverse association between leisure time physical activity and stroke risk. 5 7 Small sample sizes and few stroke events, especially among women, may have contributed to the inconsistent observations. Our study with a large sample size and the largest number of stroke events during follow-up reported thus far provides strong evidence for the benefits of leisure time physical activity on the prevention of stroke in men and women. The incidence rates of total stroke were 3.56 per 1000 person years in men and 2.81 per 1000 person years in women in this population, which is higher than other populations. 7,10 Only 2 studies have assessed the association between occupational activity and stroke risk, and no significant association was found. 8,12 We showed that active occupational activity was modestly associated with a lower risk of total stroke incidence when both sexes were combined but neither in men nor in women separately. This indicates that the magnitude of the effect is not very large ( 10%) and thus requires a large sample size like in our study to be detected.

4 Hu et al Different Types of Physical Activity and Stroke Risk 1997 TABLE 2. HRs of Total Stroke According to the Levels of Leisure-Time, Occupational, and Commuting Physical Activity HRs (95% CI)* Cases, No. Person Years Model 1 Model 2 Model 3 Men Leisure time physical activity Low Moderate ( ) 0.83 ( ) 0.84 ( ) High ( ) 0.72 ( ) 0.72 ( ) P for trend Light Moderate ( ) 0.89 ( ) 0.93 ( ) Active ( ) 0.89 ( ) 0.90 ( ) P for trend Walking or cycling to/from work, min/day ( ) 0.91 ( ) 0.94 ( ) ( ) 0.85 ( ) 0.88 ( ) P for trend Women Leisure time physical activity Low Moderate ( ) 0.86 ( ) 0.87 ( ) High ( ) 0.75 ( ) 0.77 ( ) P for trend Light Moderate ( ) 0.90 ( ) 0.95 ( ) Active ( ) 0.86 ( ) 0.89 ( ) P for trend Walking or cycling to/from work, min/day ( ) 0.86 ( ) 0.88 ( ) ( ) 0.85 ( ) 0.87 ( ) P for trend Men and women combined Leisure time physical activity Low Moderate ( ) 0.85 ( ) 0.86 ( ) High ( ) 0.73 ( ) 0.74 ( ) P for trend Light Moderate ( ) 0.90 ( ) 0.94 ( ) Active ( ) 0.87 ( ) 0.89 ( ) P for trend Walking or cycling to/from work, min/day ( ) 0.89 ( ) 0.92 ( ) ( ) 0.85 ( ) 0.89 ( ) P for trend *Model 1, Adjusted for age, area, and study year; model 2, additionally adjusted for BMI, SBP, cholesterol, education, smoking, alcohol consumption, and diabetes; model 3, models 2 and also adjusted for other 2 types of physical activity. Also adjusted for sex.

5 1998 Stroke September 2005 TABLE 3. HRs of Total Stroke According to Combined Levels of Leisure Time, Occupational, and Commuting Physical Activity* HRs (95% CI) Low Leisure-Time Physical Activity Moderate or High Leisure-Time Physical Activity No Active Commuting Walking or Cycling to/from Work 1 min/day No Active Commuting Walking or Cycling to/from Work 1 min/day Light occupational activity ( ) 0.81 ( ) 0.69 ( ) Moderate or active occupational activity 0.86 ( ) 0.79 ( ) 0.69 ( ) 0.69 ( ) *Adjusted for age, sex, area, study year, BMI, SBP, cholesterol, education, smoking, alcohol consumption, and diabetes. Occupational physical activity also modestly reduced the risk of ischemic stroke when both sexes were combined. We found that daily commuting activity on foot or by bicycle may reduce total stroke risk. This is an important finding because daily active commuting is a major source of total physical activity in some populations, it can be implemented virtually everywhere, and is inexpensive. For instance, in urban China, 90% of people walk or cycle to work daily. 27 In our study, 40% of the Finnish subjects reported walking or cycling to work daily. Several studies have shown that regular active commuting is related to lower levels of cardiovascular risk factors 15,28 and reduces mortality among diabetic patients. 18 Few studies have examined the association between physical activity and the risk of different subtypes of stroke, and the results are inconsistent. 3,7,11 In the Honolulu Study, 3 active men experienced a lower risk of subarachnoid hemorrhagic or intracerebral hemorrhagic stroke compared with inactive men, but no significant association of physical activity on thromboembolic stroke risk was found. In the Physicians Health Study, 11 an inverse association of leisure time physical activity on hemorrhagic stroke risk disappeared after adjustment for other confounding factors, and no significant association with ischemic stroke was present. In the Nurses Health Study, 7 regular leisure time physical activity was associated with a reduced risk of ischemic stroke only but not with subarachnoid hemorrhagic or intracerebral hemorrhagic stroke. These studies usually have a relatively small number of hemorrhagic stroke cases. The present study is, to our knowledge, the first that has found an inverse association of leisure time physical activity on the risk of each type of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. A recent meta-analysis comprising 6 ischemic and 3 hemorrhagic stroke studies indicated that highly active individuals had a reduced risk of ischemic and hemorrhagic strokes than low-active individuals, 13 in keeping with our results. However, it did not separately analyze subarachnoid hemorrhagic stroke and intracerebral hemorrhagic stroke. 13 Interestingly, only leisure time physical activity protected from subarachnoid hemorrhagic. often includes isotonic bouts of activity that are known to trigger the rupture of aneurysms and the onset of subarachnoid hemorrhagic stroke. TABLE 4. HRs of Different Subtypes of Stroke According to the Level of Leisure Time, Occupational, and Commuting Physical Activity* Cases, No. Subarachnoid Hemorrhagic Stroke Intracerebral Hemorrhagic Stroke Ischemic Stroke Person Years HRs (95% CI) Cases, No. Person Years HRs (95% CI) Cases, No. Person Years HRs (95% CI) Leisure time physical activity Low Moderate ( ) ( ) ( ) High ( ) ( ) ( ) P for trend Light Moderate ( ) ( ) ( ) Active ( ) ( ) ( ) P for trend Walking or cycling to/from work, min/day ( ) ( ) ( ) ( ) ( ) ( ) P for trend *Adjusted for age, sex, area, study year, BMI, SBP, cholesterol, education, smoking, alcohol consumption, diabetes, and other 2 types of physical activity.

6 Hu et al Different Types of Physical Activity and Stroke Risk 1999 The protective effect of physical activity may partly mediate through its effect on other risk factors of stroke. 29 Physical activity has a favorable effect on blood pressure, lipid profile, insulin sensitivity, body weight, blood coagulation, and fibrinolysis 10,15,17,28,30,31 and also reduces the risk of hypertension and diabetes. 15,17,19 In our study, the inverse associations between physical activity and stroke risk remained significant also after controlling for the major cardiovascular risk factors. There are several strengths and limitations in our study. Our study is population based, comprising a large number of men and women from a homogeneous population. The mean followup, 19.0 years, was long enough that the largest number of stroke events were ascertained without loss of follow-up. Not only leisure time physical activity but also occupational and commuting physical activities were included in the analysis. Moreover, the subtypes of stroke were also analyzed. A limitation of our study was the self-report of physical activity. Using a questionnaire to assess habitual physical activity is always crude and imprecise. We do not have data on possible changes in physical activity during follow-up. Misclassification, particularly over-reporting the amount of physical activity at baseline and changes in the activity during follow-up, probably lead to an underestimation of the association between physical activity and the outcome. We cannot completely exclude either the effects of residual confounding attributable to the measurement error in the assessment of confounding factors or some unmeasured dietary factors. In conclusion, our study demonstrates that a higher level of leisure time physical activity reduces total and different subtypes of stroke risk. Commuting physical activity is inversely associated with ischemic stroke but not for subarachnoid and intracerebral hemorrhagic strokes. Acknowledgments This study was supported by grants from the Finnish Academy (46558, , and ), the Ministry of Education, and the Finnish Foundation for Cardiovascular Research. References 1. Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C, Buchner D, Ettinger W, Heath GW, King AC, Kiska A, Leon AS, Marcus BH, Morris J, Paffenbarger RS, Patrick K, Pollock ML, Rippe JM, Sallis J, Wilmore JH. Physical activity and public health. A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. J Am Med Assoc. 1995;273: Wannamethee G, Shaper AG. Physical activity and stroke in British middle aged men. BMJ. 1992;304: Abbott RD, Rodriguez BL, Burchfiel CM, Curb JD. Physical activity in older middle-aged men and reduced risk of stroke: the Honolulu Heart Program. Am J Epidemiol. 1994;139: Kiely DK, Wolf PA, Cupples LA, Beiser AS, Kannel WB. Physical activity and stroke risk: the Framingham Study. Am J Epidemiol. 1994;140: Gillum RF, Mussolino ME, Ingram DD. Physical activity and stroke incidence in women and men: the NHANES I epidemiologic follow-up study. Am J Epidemiol. 1996;143: Ellekjaer H, Holmen J, Ellekjaer E, Vatten L. Physical activity and stroke mortality in women: ten-year follow-up of the Nord-Trondelag Health Survey, Stroke. 2000;31: Hu FB, Stampfer MJ, Colditz GA, Ascherio A, Rexrode KM, Willett WC, Manson JE. Physical activity and risk of stroke in women. JAmMed Assoc. 2000;283: Menotti A, Keys A, Blackburn H, Aravanis C, Dontas A, Fidanza F, Giampaoli S, Karvonen M, Kromhout D, Nedeljkovic S, et al. Twenty-year stroke mortality and prediction in twelve cohorts of the Seven Countries Study. Int J Epidemiol. 1990;19: Lindsted KD, Tonstad S, Kuzma JW. Self-report of physical activity and patterns of mortality in Seventh-Day Adventist men. J Clin Epidemiol. 1991;44: Lee IM, Paffenbarger RS Jr. Physical activity and stroke incidence: the Harvard Alumni Health Study. Stroke. 1998;29: Lee IM, Hennekens CH, Berger K, Buring JE, Manson JE. Exercise and risk of stroke in male physicians. Stroke. 1999;30: Evenson KR, Rosamond WD, Cai J, Toole JF, Hutchinson RG, Shahar E, Folsom AR. Physical activity and ischemic stroke risk: the Atherosclerosis Risk in Communities Study. Stroke. 1999;30: Lee CD, Folsom AR, Blair SN. Physical activity and stroke risk: a meta-analysis. Stroke. 2003;34: Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P, Puska P. Cardiovascular risk factor changes in Finland, Int J Epidemiol. 2000;29: Hu G, Qiao Q, Silventoinen K, Eriksson JG, Jousilahti P, Lindstrom J, Valle TT, Nissinen A, Tuomilehto J. Occupational, commuting, and leisure-time physical activity in relation to risk for type 2 diabetes in middle-aged Finnish men and women. Diabetologia. 2003;46: Barengo NC, Hu G, Lakka TA, Pekkarinen H, Nissinen A, Tuomilehto J. Low physical activity as a predictor for total and cardiovascular disease mortality in middle-aged men and women in Finland. Eur Heart J. 2004;25: Hu G, Barengo NC, Tuomilehto J, Lakka TA, Nissinen A, Jousilahti P. Relationship of physical activity and body mass index to the risk of hypertension: a prospective study in Finland. Hypertension. 2004;43: Hu G, Eriksson J, Barengo NC, Lakka TA, Valle TT, Nissinen A, Jousilahti P, Tuomilehto J. Occupational, commuting, and leisure-time physical activity in relation to total and cardiovascular mortality among Finnish subjects with type 2 diabetes. Circulation. 2004;110: Hu G, Lindstrom J, Valle TT, Eriksson JG, Jousilahti P, Silventoinen K, Qiao Q, Tuomilehto J. Physical activity, body mass index, and risk of type 2 diabetes in patients with normal or impaired glucose regulation. Arch Intern Med. 2004;164: Hu G, Tuomilehto J, Silventoinen K, Barengo N, Jousilahti P. Joint effects of physical activity, body mass index, waist circumference and waist-to-hip ratio with the risk of cardiovascular disease among middle-aged Finnish men and women. Eur Heart J. 2004;25: Barengo NC, Hu G, Kastarinen M, Lakka TA, Pekkarinen H, Nissinen A, Tuomilehto J. Low physical activity as a predictor for antihypertensive drug treatment in year-old populations in Eastern and South- Western Finland. J Hypertens. 2005;23: Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care. 2005;28: Keys A. Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease. Cambridge, Mass: Harvard University Press; Albanes D, Conway JM, Taylor PR, Moe PW, Judd J. Validation and comparison of eight physical activity questionnaires. Epidemiology. 1990;1: Leppälä JM, Virtamo J, Heinonen OP. Validation of stroke diagnosis in the National Hospital Discharge Register and the Register of Causes of Death in Finland. Eur J Epidemiol. 1999;15: Cox DR. Regression models and life tables (with discussion). J R Stat Soc Ser B Stat Soc. 1972;34: Hu G, Pekkarinen H, Hanninen O, Yu Z, Tian H, Guo Z, Nissinen A. Physical activity during leisure and commuting in Tianjin, China. Bull World Health Organ. 2002;80: Hu G, Pekkarinen H, Hanninen O, Yu Z, Guo Z, Tian H. Commuting, leisure-time physical activity, and cardiovascular risk factors in China. Med Sci Sports Exercise. 2002;34: Gorelick PB, Sacco RL, Smith DB, Alberts M, Mustone-Alexander L, Rader D, Ross JL, Raps E, Ozer MN, Brass LM, Malone ME, Goldberg S, Booss J, Hanley DF, Toole JF, Greengold NL, Rhew DC. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. J Am Med Assoc. 1999; 281: Gris JC, Schved JF, Feugeas O, Aguilar-Martinez P, Arnaud A, Sanchez N, Sarlat C. Impact of smoking, physical training and weight reduction on FVII, PAI-1 and hemostatic markers in sedentary men. Thromb Haemost. 1990;64: Mayer-Davis EJ, D Agostino R Jr, Karter AJ, Haffner SM, Rewers MJ, Saad M, Bergman RN. Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. J Am Med Assoc. 1998;279:

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