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Physical activity and cardiovascular disease prevention in women: A review of the epidemiologic evidence
Nutrition, Metabolism & Cardiovascular Diseases (2010) 20, 467e473
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/nmcd
REVIEW
Physical activity and cardiovascular disease prevention in women: A review of the epidemiologic evidence S.S. Bassuk a, J.E. Manson a,b,* a b
Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, MA 02215, USA Harvard Medical School, USA
Received 1 June 2009; received in revised form 17 November 2009; accepted 23 December 2009
KEYWORDS Cardiovascular disease; Coronary heart disease; Exercise; Physical activity; Prevention; Stroke; Women
Abstract Epidemiologic studies suggest that as little as 30 minutes of moderate-intensity physical activity per day can lower the risk of developing cardiovascular disease in women. Sedentary individuals who become physically active even at older ages derive cardiovascular benefits. Physical activity appears to slow the initiation and progression of CVD through salutary effects not only on adiposity but also on insulin sensitivity, glycemic control, incident type 2 diabetes, blood pressure, lipids, endothelial function, hemostasis, and inflammatory defense systems. Public health initiatives that promote moderate increases in physical activity may offer the best balance between efficacy and feasibility to improve cardiovascular health in sedentary populations. ª 2010 Elsevier B.V. All rights reserved.
To lower risk for cardiovascular disease (CVD) and improve health, the U.S. Surgeon General, the American Heart Association (AHA), and the American College of Sports Medicine (ACSM) have long recommended that adults
* Corresponding author. Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, MA 02215, USA. Tel.: þ1 617 278 0871; fax: þ1 617 731 3843. E-mail addresses: [email protected] (S.S. Bassuk), [email protected] (J.E. Manson).
perform at least 30 minutes of moderate-intensity physical activity on most days of the week or, alternatively, vigorous-intensity physical activity for at least 20 minutes on three days of the week [1e3]. The U.S. Department of Health and Human Services recently issued a similar guidelinedat least 150 minutes per week of moderateintensity physical activity, or 75 minutes per week of vigorous-intensity physical activity [4]. However, only 28% of U.S. women and 31% of men exercise enough to meet these guidelines, and 41% of women and 39% of men engage in no leisure-time physical activity at all [5].
0939-4753/$ - see front matter ª 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2009.12.015
468
Cardiovascular benefits of walking: the evidence Exercise intensity is typically measured in kilocalories (kcal) burned per minute of activity or in metabolic equivalents (METs), defined as the ratio of the metabolic rate during exercise to the metabolic rate at rest. Moderate-intensity activities, such brisk walking, are those that burn 3.5 to 7 kcal per minute or, equivalently, those that expend 3 to 6 METs. Vigorous activities, such as running, are those that burn more than 7 kcal per minute or expend more than 6 METs. Findings from prospective observational studies published during the last decade strongly support the prescription of either vigorous or moderate-intensity physical activity for CVD prevention in sedentary women [6]. Among 73,000 postmenopausal participants aged 50 to 79 years in the Women’s Health Initiative Observational Study, walking briskly for at least 2.5 hours per week (e.g., a half-hour five times per week) was associated with a 30% reduction in cardiovascular events over a 3-year follow-up period [7]. After controlling for total exercise energy expenditure, brisk walking and more vigorous exercise were associated with similar risk reductions in cardiovascular events, and the results did not vary substantially by race, age, or baseline body mass index (Fig. 1). Prolonged sitting also predicted an increased risk of CVD, even after accounting for time spent in recreational exercise. Women who spent 16 or more hours per day sitting were 68% more likely to develop CVD than those who spent less than 4 hours per day sitting. Cardiovascular benefits of walkingdthe most common leisure activity among U.S. adultsdhave also been observed in many other studies of women. For example, among 72,000 healthy middle-aged female nurses followed for 8 years in the Nurses’ Health Study, three hours per week of brisk walking had the same protective effect as 1.5 hours per week of vigorous exercise [8]. Women reporting either type of exercise were 30 to 40% less likely to develop myocardial infarction than their sedentary counterparts. Among 39,000 healthy middle-aged female health professionals followed for 7 years in the Women’s Health Study, walking at least one hour per week predicted a 50% reduction in risk for coronary heart disease (CHD) in participants reporting no vigorous physical activity such as running or bicycling [9]. In a 30-year follow-up of 1564 middle-aged University of Pennsylvania alumnae, walking 10 or more blocks per day as compared with walking less than 4 blocks per day was associated with a 33% reduction in incident CVD [10]. In the Study of Osteoporotic Fractures, which followed 9704 women aged 65 years or older for 10 years, participants whose weekly walking energy expenditures averaged 300 or more kilocalories (about 1 hour of walking per week) were 34% less likely to die from a cardiovascular cause than were those with weekly walking energy expenditures of less than 70 kilocalories [11]. Cardiovascular benefits of walking and other moderateintensity activities have also been reported in males, although somewhat less strongly, perhaps because background activity levels in men are generally higher than those in women. Nevertheless, in the Health Professionals Follow-up Study, which followed 44,000 male health professionals aged 40 to 75 years for 12 years, one half-hour
S.S. Bassuk, J.E. Manson per day or more of brisk walking was associated with an 18% reduction in CHD incidence [12]. Also, among 253,000 women and men aged 50 to 71 years who were followed for an average of 5 years in the National Institutes of HealthAARP Diet and Health Study, engaging in physical activity of at least moderate intensity for more than 3 hours per week predicted a 29% decreased risk for cardiovascular mortality compared with no physical activity, while engaging in vigorous exercise for 20 minutes three or more times per week predicted a 33% reduction in risk [13]. Although sex-specific results were not presented for cardiovascular outcomes, the relation between physical activity and total mortality was similar for women and for men. Among those with little vigorous activity, women and men who engaged in recommended levels of moderatephysical activity were 35% and 40% less likely to die, respectively, than their inactive counterparts. Studies in men suggest that vigorous exercise is even more beneficial than moderate-intensity exercise for CVD risk reduction [12,14e16].
Physical activity and stroke Although data are less extensive and consistent than for CHD outcomes, prospective studies also report that physical activity is associated with a reduced incidence of stroke. A meta-analysis of 18 cohort studies with follow-up periods ranging from 5 to 26 years found that moderately active and highly active individuals were 17% and 25% less likely to have a stroke or die from stroke-related causes than were individuals with low activity [17]. On the basis of six ischemic and three hemorrhagic stroke studies in the meta-analysis, physical activity appears to protect against both types of stroke. Compared with low-activity individuals, moderately active persons had a 9% and 15% lower risk of ischemic and hemorrhagic stroke, respectively; the corresponding risk reductions for highly active persons were 21% and 34%. However, variation in how physical activity was measured and classified in the original studies did not allow a precise definition of ‘‘high,’’ ‘‘moderate,’’ and ‘‘low’’ activity. Moreover, sex-specific estimates were not provided, despite the fact that eight of the 18 studies included female participants. In the Nurses’ Health Study, there was a strong inverse gradient of risk with volume of physical activity [18], primarily due to the relation with ischemic rather than hemorrhagic stroke; the most active women experienced just half the risk for ischemic stroke as the least active women. More recently, a 19-year follow-up of nearly 48,000 Finnish adults aged 25e64 found that amounts of leisure-time, occupational, and commuting physical activity were each inversely related to the risk for stroke [19]. For example, participants who reported walking or cycling to work for 30 minutes or more per day were 11% less likely to develop stroke than their counterparts with no commuting physical activity. The strength of the associations was similar for women and men.
Never too late for CVD benefits Although most of the aforementioned studies did not investigate physical activity patterns across the lifespan,
Physical activity and cardiovascular disease prevention in women
469
Ethnicity
1.0 0.82
1.2
0.73 1.0
0.63
1.0
0.55
0.8
0.81
0.6
0.68
0.58
White (N=61,574) p, trend <0.001
0.48
0.4
Black (N=5,661) p, trend = 0.02
0.2
Age-Adjusted Relative Risk for Cardiovascular Disease
0.0
1 (Lowest)
2
3
5 (Highest)
4
Age
1.0 0.93 0.86 0.75
1.0
0.64
1.2 1.0
0.79 1.0
0.63 0.56
0.8
70-79 years (N=15,856) p, trend <0.001
0.50 0.68
0.6
0.63
60-69 years (N=32,127) p, trend <0.001
0.54 0.4
0.45
0.2 0.0
50-59 years (N=24,803) p, trend <0.001 1 (Low e s t)
2
3
4
5 (Highest)
Body Mass Index (BMI)
1.0 0.96 0.65
1.2 1.0
0.80
0.73
1.0
0.67
0.82
0.71
1.0
0.58
0.8
0.75
0.84
0.6
0.61
BMI 30+ (N=16,806) p, trend = 0.007
0.60 BMI 25-<30 (N=24,590) p, trend <0.001
0.4 0.2 0.0
1 (Low e s t)
2
3
4
5 (Highe s t)
BMI <25 (N=30,583) p, trend <0.001
Total METs Score Quintile
Figure 1 Age-adjusted relative risks for cardiovascular disease according to quintile of energy expenditure from recreational activities in subgroups defined by race, age, and body mass index. Quintile medians (ranges), in MET- hours per week, are as follows: quintile 1, 0 (0e2.4); quintile 2, 4.2 (2.5e7.2); quintile 3, 10.0 (7.3e13.4); quintile 4, 17.5 (13.5e23.3); quintile 5, 32.8 (23.4). Quintile 1 is the reference category. Adapted from: Manson JE et al., N Engl J Med 2002; 347:716e25. Copyright ª2002, Massachusetts Medical Society. All rights reserved.
470 other research indicates that previously sedentary individuals who become physically active in middle or late life derive cardiovascular benefits. A 10-year follow-up of two groups of initially inactive healthy women and men aged 55 to 75 years, one comprised of individuals who chose to participate in a supervised exercise program (30 to 45 minutes of walking three times per week) and the other of community controls, found that the exercise group experienced more favorable changes in systolic blood pressure, high-density lipoprotein and total cholesterol, triglycerides, insulin, waist circumference, and percent body fat, as well as fewer abnormal electrocardiogram findings on exercise treadmill testing [20]. Among initially sedentary participants in the Nurses’ Health Study, 6-year changes in activity level were significantly associated in dose-response fashion with CHD incidence during the subsequent 8 years [8]. Compared with women who remained sedentary, women with increasing quintiles of total physical activity energy expenditure were 15%, 21%. 33%, and 29% less likely to have a coronary event. In the Study of Osteoporotic Fractures, which assessed changes in physical activity over 6 years among 7553 women aged 65 years or older at baseline, women who increased their physical activity were 36% less likely to die from cardiovascular causes during the subsequent 7 years than were women who remained sedentary [11]. However, exercise must be current and habitual to confer cardiovascular protection; women who became inactive in later life had a similar risk of cardiovascular mortality as those who had remained inactive over the course of follow-up. From a public health perspective, knowing that ‘‘it’s never too late’’ may motivate older individuals to shed their sedentary lifestyle.
Short bouts of exercise Bouts of activity as short as 10 to 15 minutes have been shown to affect favorably the cardiovascular risk profile of otherwise sedentary persons [21e23]. One prospective study has examined the relation between brief bouts of exercise and clinical CVD. After controlling for total energy expenditure, exercise sessions lasting 15, 30, or 45 minutes offered equal protection against incident CVD in a cohort of 7307 middle-aged and elderly male Harvard alumni followed for 5 years [24]. Although there are no studies of this issue in women, it is not unreasonable to speculate that similar results would be observed. These findings may help motivate busy individuals to view exercise as a manageable part of their daily routine rather than as a time-consuming activity reserved for rare occasions.
S.S. Bassuk, J.E. Manson non-cardiovascular benefits, including the preservation of bone density and musculoskeletal function [25], which is particularly important for women, as they are more susceptible to osteoporotic fracture than are men. Yet only 17.5% of U.S. women engage in strength training at least twice per week [26], as recommended by current guidelines [25,27].
Cardiorespiratory fitness The above studies, in which self-reported physical activity served as the predictor variable, offer direct support for CVD prevention guidelines, which target physical activity, a behavior, rather than physical fitness, a physiologic parameter. In addition, several studies have shown cardiorespiratory fitness as assessed by maximal treadmill exercise test to be significantly inversely correlated with cardiovascular mortality in individuals without coronary symptoms at baseline. For example, among 2994 women aged 30 to 80 years followed for two decades in the Lipid Research Clinics Study, the risk for cardiovascular mortality decreased by 17% for every 1-MET increment in exercise capacity, after adjustment for multiple risk factors [28]. In an 8-year follow-up of 5636 women aged 35 years and older (the St James Women Take Heart Study), cardiac mortality declined by 22% for each 1-MET increase in exercise capacity, after adjustment for coronary risk profile [29]. A recent meta-analysis of data from 24 prospective cohorts with a total of 84,323 initially healthy participants (the majority were men) and 4485 CVD endpoints (many studies considered only cardiovascular mortality) found a significant 15% decline in cardiovascular risk for each 1-MET increase in exercise capacity [30]; the relation was similar in the 16 studies that included only men (risk reduction, 14%) and in the eight studies that included both sexes or only women (risk reduction, 16%). However, data on the relation between cardiorespiratory fitness and risk for nonfatal cardiovascular events in women are sparse. In modestly sized cohorts of relatively young women, researchers from the Aerobics Center Longitudinal Study [31] (5909 female participants, 82% of whom were younger than age 55) and Framingham Heart Study [32] (1612 female participants, average age of 45) reported suggestive but nonsignificant inverse relations between exercise capacity and incidence of (a) nonfatal CVD and (b) fatal plus nonfatal CHD, respectively, after adjustment for traditional coronary risk factors.
Protective mechanisms Weight control
Resistance exercise Although aerobic exercise has been the focus of most epidemiologic investigations of physical activity to date, there is growing recognition that resistance exercise may also reduce cardiovascular risk. In the Health Professionals Follow-up Study, men who trained with weights for at least 30 minutes per week were 23% less likely to develop CHD during an 8-year follow-up than men who did not train with weights [12]. Aerobic and resistance exercise also confer
Together with caloric intake, physical activity is a key determinant of energy balance and thus degree of adiposity. Obesity is an established cardiovascular risk factor; prospective studies in female populations indicate that an estimated 25% of CHD cases are attributable to excess weight and that each kilogram of weight gained during midlife increases CHD risk by 3% [33]. It is thus likely that one pathway by which physical activity attenuates cardiovascular risk is via regulation of body weight. Indeed,
Physical activity and cardiovascular disease prevention in women the Institute of Medicine highlighted the issue of weight control in its controversial 2002 recommendation espousing 60drather than 30dminutes per day of physical activity for weight maintenance and maximal health benefits [34]. From a public health perspective, this recommendation may not have made a clear enough distinction between the goal of weight control and the goal of disease risk reduction nor given enough attention to balancing efficacy and feasibility considerations [35,36]. Subsequently, while acknowledging that higher activity levels lead to greater cardiovascular risk reduction, the American Heart Association and American College of Sports Medicine reaffirmed the 30-minute guideline for prevention of CVD [2,3]. The latter organization recently reviewed the empirical literature on physical activity in relation to weight control and concluded that, in the absence of caloric restriction, 150e250 minutes per week of moderate-intensity activity appears to be effective for preventing weight gain but not for producing clinically significant weight loss, while more than 250 minutes per week of such activity appears to be necessary for clinically significant weight loss as well as for the prevention of weight gain following weight loss [37]. Although weight control is an important goal, focusing on it as the main reason for engaging in physical activity gives an incomplete assessment of exercise’s impact on cardiovascular health. With few exceptions, prospective observational studies find that inverse relations between physical activity and risk for CVD persist even after factoring out the effects of body mass index, suggesting that the cardiovascular benefits derived from physical activity are not solely attributable to weight regulation. Moreover, as shown in Fig. 2, data from the Nurses’ Health Study indicate that physical inactivity and obesity independently contribute to the development of CHD in initially healthy women [38]. Findings from other large cohorts are similar [39e41].
Other mechanisms Physical activity appears to slow the initiation and progression of CVD through beneficial effects not only on adiposity but also on insulin sensitivity, glycemic control,
471
Table 1 Proposed ‘‘Prescription’’.
elements
for
an
exercise
Take the stairs whenever possible. Purchase a pedometer and aim for 10,000 steps per day. Display ‘‘exercise prescription’’ in a visible place. If you drive to work or stores, park in a space far away from the door and walk. If you take public transportation, get off a stop early and walk. Walk on your lunch break. Try exercising with friends or a group. Add strength training for 20 minutes 2e3 times per week.
Source: Manson JE et al., Arch Intern Med 2004; 164:249e58. Copyright ª2004, American Medical Association. All rights reserved.
type 2 diabetes incidence, blood pressure, lipids, endothelial function, hemostasis, and inflammatory defense systems [42]. In the Women’s Health Study, these factors explained 59% of the observed inverse relation between physical activity and incident CVD over an 11-year followup period [43]. Inflammatory/hemostatic risk factors (C-reactive protein, fibrinogen, and soluble intercellular adhesion molecule-1) made the largest contribution to lower risk (32.5%), followed by blood pressure (27.1%), traditional lipids (19.1%), the novel lipids lipoprotein(a) and apolipoproteins A1 and B-100 (15.5%), body mass index (10.1%), and hemoglobin A1c/diabetes (8.9%). Findings from observational studies and randomized trials indicate that regular moderate-intensity activity is as effective as more vigorous activity in reducing blood pressure and improving insulin sensitivity [42]. (A recent randomized trial in patients with type 2 diabetes found that a combination of aerobic and resistance exercise yielded greater improvement in glycemic control than did either type of exercise alone [44].) In contrast, strong dose-response associations between exercise intensity and blood lipidsdspecifically, triglycerides and high-density lipoprotein cholesteroldhave been reported [42].
Conclusion 3.4
3.3
3.5
2.5
Relative risk*
3 2.5
2.0
1.9
2 1.5
1.4 1.5
1
30+
1.3
25 - 29.9 x (k e
1.0
0.5
<25
0
<1
1-3.5
3.5+
Physical activity (hours/week)
B
ym od
s as
2
m g/
)
ind
Figure 2 Relative risk for coronary heart disease according to body mass index and physical activity level, Nurses’ Health Study, 1980e2000. *Relative risks are adjusted for age, smoking status, alcohol consumption, menopausal status, postmenopausal hormone use, aspirin use, and parental history of CHD. Data from: Li TY et al., Circulation 2006;113:499e506.
Epidemiologic studies suggest that as little as 30 minutes per day of brisk walking or other moderate-intensity physical activity can reduce the incidence of clinical cardiovascular events in women. In a sedentary society such as the United States, a key challenge to clinicians and policymakers is identifying strategies to facilitate sustained physical activity at a level sufficient to result in measurable improvements in health. Based on our review of available scientific data, we believe that the clinical and public health message regarding exercise for CVD prevention should remain ‘‘30 minutes per day of moderate activity is beneficial, although more is better, to a reasonable extent.’’ Although more than 2 in 3 adults do not exercise enough to meet the 30-minute guideline, only 1 in 3 persons in the U.S. who saw a physician in the prior year received physical activity counseling at their last visit, according to National
472 Health Interview Survey data [45]. However, a survey of primary-care physicians in Canada found that 70% reported routinely counseling patients about physical activity [46]. Although the prevalence of clinician counseling remains unclear, failure to counsel is often attributed to lack of time, training, and appropriate patient materials, yet such counseling need not be time intensive or intricate. Data from the multi-center Activity Counseling Trial suggest that clinicians can easily learn to incorporate 3 to 4 minutes of physical activity advice into routine office visits [47] and that counseling can help sedentary patients become more active [48]. A simple blueprint for physicians who are perplexed about how to incorporate brief counseling about physical activity into their daily practices was published in a recent commentary [49]. Lay publications to help sedentary women and older individuals increase their activity level are available online at no charge from the American Heart Association [50], the National Institute on Aging [51], the National Heart, Lung and Blood Institute [52], and the U.S. Department of Health and Human Services [4]. Possible elements for an exercise ‘‘prescription’’ for patients are listed in Table 1. Data from randomized trials suggest that ‘‘lifestyle activity’’ interventions, which encourage individuals to incorporate short bouts of physical activity into their daily life (e.g., taking walks during lunch breaks, doing yard work or gardening, and using the stairs instead of the elevator), can be more effective than formal exercise programs in boosting activity levels and improving fitness and cardiovascular risk profiles [53]. The use of self-monitoring strategies such as pedometers or exercise diaries also promotes daily activity. In a meta-analysis of data from 26 studies (including 8 randomized trials) in which 85% of the participants were women, pedometer use led to a significant 27% increase in physical activity as well as significant reductions in body mass index and blood pressure [54]. More research on the characteristics of other individualand community-based interventions, initiatives, and policies that promote healthful exercise behaviors are needed [55]. Given the high prevalence of sedentary behavior, a widespread effort to help patients achieve even modest increases in regular physical activity will likely favorably influence cardiovascular morbidity and mortality. As the eminent British epidemiologist Geoffrey Rose has observed [56], the overall disease burden in a given population generally undergoes a more dramatic reduction when a large segment of the population adopts small improvements in health behaviors than when a small segment of the population adopts large improvements.
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[40]
[41]
[42]
[43]
[44]
[45] [46]
[47]
[48]
[49]
[50]
[51]
[52]
[53] [54]
[55]
[56]
473 cardiovascular disease in men and women in the Lipid Research Clinics study. Am J Epidemiol 2002;156:832e41. Vatten LJ, Nilsen TI, Romundstad PR, Droyvold WB, Holmen J. Adiposity and physical activity as predictors of cardiovascular mortality. Eur J Cardiovasc Prev Rehabil 2006;13:909e15. Weinstein AR, Sesso HD, Lee IM, Rexrode KM, Cook NR, Manson JE, et al. The joint effects of physical activity and body mass index on coronary heart disease risk in women. Arch Intern Med 2008;168:884e90. Bassuk SS, Manson JE. Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol 2005;99:1193e204. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 2007;116:2110e8. Sigal RJ, Kenny GP, Boule NG, Wells GA, Prud’homme D, Fortier M, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 2007;147:357e69. Wee CC, McCarthy EP, Davis RB, Phillips RS. Physician counseling about exercise. JAMA 1999;282:1583e8. Petrella RJ, Lattanzio CN, Overend TJ. Physical activity counseling and prescription among Canadian primary care physicians. Arch Intern Med 2007;167:1774e81. Albright CL, Cohen S, Gibbons L, Miller S, Marcus B, Sallis J, et al. Incorporating physical activity advice into primary care: physician-delivered advice within the Activity Counseling Trial. Am J Prev Med 2000;18:225e34. Writing Group for the Activity Counseling Trial Research Group. Effects of physical activity counseling in primary care: the Activity Counseling Trial: a randomized controlled trial. JAMA 2001;286:677e87. Manson JE, Skerrett PJ, Greenland P, VanItallie TB. The escalating pandemics of obesity and sedentary lifestyle. A call to action for clinicians. Arch Intern Med 2004;164:249e58. American Heart Association. Choose to move handbook. Dallas TX: American Heart Association. Available at: http://www. choosetomove.org/; 2004 [accessed 28.5.09]. National Institute on Aging. Exercise & physical activity: your everyday guide from the National Institute on Aging. Bethesda MD: National Institute on Aging. Available at: http://www.nia. nih.gov/HealthInformation/Publications/ExerciseGuide/; 2007 [accessed 28.5.09]. National Heart, Lung and Blood Institute. Your guide to physical activity and your heart. National Heart Lung and Blood Institute. NIH Publication #06-5714. Available at: http://www.nhlbi.nih.gov/health/public/heart/obesity/phy_ active.pdf; 2006 [accessed 28.5.09]. Pratt M. Benefits of lifestyle activity vs structured exercise. JAMA 1999;281:375e6. Bravata DM, Smith-Spangler C, Sundaram V, Gienger AL, Lin N, Lewis R, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA 2007;298: 2296e304. Task Force on Community Preventive Services. Recommendations to increase physical activity in communities. Am J Prev Med 2002;22:67e72. Rose G. The strategy of preventive medicine. New York: Oxford University Press; 1992.
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REVIEW
Physical activity and cardiovascular disease prevention in women: A review of the epidemiologic evidence S.S. Bassuk a, J.E. Manson a,b,* a b
Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, MA 02215, USA Harvard Medical School, USA
Received 1 June 2009; received in revised form 17 November 2009; accepted 23 December 2009
KEYWORDS Cardiovascular disease; Coronary heart disease; Exercise; Physical activity; Prevention; Stroke; Women
Abstract Epidemiologic studies suggest that as little as 30 minutes of moderate-intensity physical activity per day can lower the risk of developing cardiovascular disease in women. Sedentary individuals who become physically active even at older ages derive cardiovascular benefits. Physical activity appears to slow the initiation and progression of CVD through salutary effects not only on adiposity but also on insulin sensitivity, glycemic control, incident type 2 diabetes, blood pressure, lipids, endothelial function, hemostasis, and inflammatory defense systems. Public health initiatives that promote moderate increases in physical activity may offer the best balance between efficacy and feasibility to improve cardiovascular health in sedentary populations. ª 2010 Elsevier B.V. All rights reserved.
To lower risk for cardiovascular disease (CVD) and improve health, the U.S. Surgeon General, the American Heart Association (AHA), and the American College of Sports Medicine (ACSM) have long recommended that adults
* Corresponding author. Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, MA 02215, USA. Tel.: þ1 617 278 0871; fax: þ1 617 731 3843. E-mail addresses: [email protected] (S.S. Bassuk), [email protected] (J.E. Manson).
perform at least 30 minutes of moderate-intensity physical activity on most days of the week or, alternatively, vigorous-intensity physical activity for at least 20 minutes on three days of the week [1e3]. The U.S. Department of Health and Human Services recently issued a similar guidelinedat least 150 minutes per week of moderateintensity physical activity, or 75 minutes per week of vigorous-intensity physical activity [4]. However, only 28% of U.S. women and 31% of men exercise enough to meet these guidelines, and 41% of women and 39% of men engage in no leisure-time physical activity at all [5].
0939-4753/$ - see front matter ª 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2009.12.015
468
Cardiovascular benefits of walking: the evidence Exercise intensity is typically measured in kilocalories (kcal) burned per minute of activity or in metabolic equivalents (METs), defined as the ratio of the metabolic rate during exercise to the metabolic rate at rest. Moderate-intensity activities, such brisk walking, are those that burn 3.5 to 7 kcal per minute or, equivalently, those that expend 3 to 6 METs. Vigorous activities, such as running, are those that burn more than 7 kcal per minute or expend more than 6 METs. Findings from prospective observational studies published during the last decade strongly support the prescription of either vigorous or moderate-intensity physical activity for CVD prevention in sedentary women [6]. Among 73,000 postmenopausal participants aged 50 to 79 years in the Women’s Health Initiative Observational Study, walking briskly for at least 2.5 hours per week (e.g., a half-hour five times per week) was associated with a 30% reduction in cardiovascular events over a 3-year follow-up period [7]. After controlling for total exercise energy expenditure, brisk walking and more vigorous exercise were associated with similar risk reductions in cardiovascular events, and the results did not vary substantially by race, age, or baseline body mass index (Fig. 1). Prolonged sitting also predicted an increased risk of CVD, even after accounting for time spent in recreational exercise. Women who spent 16 or more hours per day sitting were 68% more likely to develop CVD than those who spent less than 4 hours per day sitting. Cardiovascular benefits of walkingdthe most common leisure activity among U.S. adultsdhave also been observed in many other studies of women. For example, among 72,000 healthy middle-aged female nurses followed for 8 years in the Nurses’ Health Study, three hours per week of brisk walking had the same protective effect as 1.5 hours per week of vigorous exercise [8]. Women reporting either type of exercise were 30 to 40% less likely to develop myocardial infarction than their sedentary counterparts. Among 39,000 healthy middle-aged female health professionals followed for 7 years in the Women’s Health Study, walking at least one hour per week predicted a 50% reduction in risk for coronary heart disease (CHD) in participants reporting no vigorous physical activity such as running or bicycling [9]. In a 30-year follow-up of 1564 middle-aged University of Pennsylvania alumnae, walking 10 or more blocks per day as compared with walking less than 4 blocks per day was associated with a 33% reduction in incident CVD [10]. In the Study of Osteoporotic Fractures, which followed 9704 women aged 65 years or older for 10 years, participants whose weekly walking energy expenditures averaged 300 or more kilocalories (about 1 hour of walking per week) were 34% less likely to die from a cardiovascular cause than were those with weekly walking energy expenditures of less than 70 kilocalories [11]. Cardiovascular benefits of walking and other moderateintensity activities have also been reported in males, although somewhat less strongly, perhaps because background activity levels in men are generally higher than those in women. Nevertheless, in the Health Professionals Follow-up Study, which followed 44,000 male health professionals aged 40 to 75 years for 12 years, one half-hour
S.S. Bassuk, J.E. Manson per day or more of brisk walking was associated with an 18% reduction in CHD incidence [12]. Also, among 253,000 women and men aged 50 to 71 years who were followed for an average of 5 years in the National Institutes of HealthAARP Diet and Health Study, engaging in physical activity of at least moderate intensity for more than 3 hours per week predicted a 29% decreased risk for cardiovascular mortality compared with no physical activity, while engaging in vigorous exercise for 20 minutes three or more times per week predicted a 33% reduction in risk [13]. Although sex-specific results were not presented for cardiovascular outcomes, the relation between physical activity and total mortality was similar for women and for men. Among those with little vigorous activity, women and men who engaged in recommended levels of moderatephysical activity were 35% and 40% less likely to die, respectively, than their inactive counterparts. Studies in men suggest that vigorous exercise is even more beneficial than moderate-intensity exercise for CVD risk reduction [12,14e16].
Physical activity and stroke Although data are less extensive and consistent than for CHD outcomes, prospective studies also report that physical activity is associated with a reduced incidence of stroke. A meta-analysis of 18 cohort studies with follow-up periods ranging from 5 to 26 years found that moderately active and highly active individuals were 17% and 25% less likely to have a stroke or die from stroke-related causes than were individuals with low activity [17]. On the basis of six ischemic and three hemorrhagic stroke studies in the meta-analysis, physical activity appears to protect against both types of stroke. Compared with low-activity individuals, moderately active persons had a 9% and 15% lower risk of ischemic and hemorrhagic stroke, respectively; the corresponding risk reductions for highly active persons were 21% and 34%. However, variation in how physical activity was measured and classified in the original studies did not allow a precise definition of ‘‘high,’’ ‘‘moderate,’’ and ‘‘low’’ activity. Moreover, sex-specific estimates were not provided, despite the fact that eight of the 18 studies included female participants. In the Nurses’ Health Study, there was a strong inverse gradient of risk with volume of physical activity [18], primarily due to the relation with ischemic rather than hemorrhagic stroke; the most active women experienced just half the risk for ischemic stroke as the least active women. More recently, a 19-year follow-up of nearly 48,000 Finnish adults aged 25e64 found that amounts of leisure-time, occupational, and commuting physical activity were each inversely related to the risk for stroke [19]. For example, participants who reported walking or cycling to work for 30 minutes or more per day were 11% less likely to develop stroke than their counterparts with no commuting physical activity. The strength of the associations was similar for women and men.
Never too late for CVD benefits Although most of the aforementioned studies did not investigate physical activity patterns across the lifespan,
Physical activity and cardiovascular disease prevention in women
469
Ethnicity
1.0 0.82
1.2
0.73 1.0
0.63
1.0
0.55
0.8
0.81
0.6
0.68
0.58
White (N=61,574) p, trend <0.001
0.48
0.4
Black (N=5,661) p, trend = 0.02
0.2
Age-Adjusted Relative Risk for Cardiovascular Disease
0.0
1 (Lowest)
2
3
5 (Highest)
4
Age
1.0 0.93 0.86 0.75
1.0
0.64
1.2 1.0
0.79 1.0
0.63 0.56
0.8
70-79 years (N=15,856) p, trend <0.001
0.50 0.68
0.6
0.63
60-69 years (N=32,127) p, trend <0.001
0.54 0.4
0.45
0.2 0.0
50-59 years (N=24,803) p, trend <0.001 1 (Low e s t)
2
3
4
5 (Highest)
Body Mass Index (BMI)
1.0 0.96 0.65
1.2 1.0
0.80
0.73
1.0
0.67
0.82
0.71
1.0
0.58
0.8
0.75
0.84
0.6
0.61
BMI 30+ (N=16,806) p, trend = 0.007
0.60 BMI 25-<30 (N=24,590) p, trend <0.001
0.4 0.2 0.0
1 (Low e s t)
2
3
4
5 (Highe s t)
BMI <25 (N=30,583) p, trend <0.001
Total METs Score Quintile
Figure 1 Age-adjusted relative risks for cardiovascular disease according to quintile of energy expenditure from recreational activities in subgroups defined by race, age, and body mass index. Quintile medians (ranges), in MET- hours per week, are as follows: quintile 1, 0 (0e2.4); quintile 2, 4.2 (2.5e7.2); quintile 3, 10.0 (7.3e13.4); quintile 4, 17.5 (13.5e23.3); quintile 5, 32.8 (23.4). Quintile 1 is the reference category. Adapted from: Manson JE et al., N Engl J Med 2002; 347:716e25. Copyright ª2002, Massachusetts Medical Society. All rights reserved.
470 other research indicates that previously sedentary individuals who become physically active in middle or late life derive cardiovascular benefits. A 10-year follow-up of two groups of initially inactive healthy women and men aged 55 to 75 years, one comprised of individuals who chose to participate in a supervised exercise program (30 to 45 minutes of walking three times per week) and the other of community controls, found that the exercise group experienced more favorable changes in systolic blood pressure, high-density lipoprotein and total cholesterol, triglycerides, insulin, waist circumference, and percent body fat, as well as fewer abnormal electrocardiogram findings on exercise treadmill testing [20]. Among initially sedentary participants in the Nurses’ Health Study, 6-year changes in activity level were significantly associated in dose-response fashion with CHD incidence during the subsequent 8 years [8]. Compared with women who remained sedentary, women with increasing quintiles of total physical activity energy expenditure were 15%, 21%. 33%, and 29% less likely to have a coronary event. In the Study of Osteoporotic Fractures, which assessed changes in physical activity over 6 years among 7553 women aged 65 years or older at baseline, women who increased their physical activity were 36% less likely to die from cardiovascular causes during the subsequent 7 years than were women who remained sedentary [11]. However, exercise must be current and habitual to confer cardiovascular protection; women who became inactive in later life had a similar risk of cardiovascular mortality as those who had remained inactive over the course of follow-up. From a public health perspective, knowing that ‘‘it’s never too late’’ may motivate older individuals to shed their sedentary lifestyle.
Short bouts of exercise Bouts of activity as short as 10 to 15 minutes have been shown to affect favorably the cardiovascular risk profile of otherwise sedentary persons [21e23]. One prospective study has examined the relation between brief bouts of exercise and clinical CVD. After controlling for total energy expenditure, exercise sessions lasting 15, 30, or 45 minutes offered equal protection against incident CVD in a cohort of 7307 middle-aged and elderly male Harvard alumni followed for 5 years [24]. Although there are no studies of this issue in women, it is not unreasonable to speculate that similar results would be observed. These findings may help motivate busy individuals to view exercise as a manageable part of their daily routine rather than as a time-consuming activity reserved for rare occasions.
S.S. Bassuk, J.E. Manson non-cardiovascular benefits, including the preservation of bone density and musculoskeletal function [25], which is particularly important for women, as they are more susceptible to osteoporotic fracture than are men. Yet only 17.5% of U.S. women engage in strength training at least twice per week [26], as recommended by current guidelines [25,27].
Cardiorespiratory fitness The above studies, in which self-reported physical activity served as the predictor variable, offer direct support for CVD prevention guidelines, which target physical activity, a behavior, rather than physical fitness, a physiologic parameter. In addition, several studies have shown cardiorespiratory fitness as assessed by maximal treadmill exercise test to be significantly inversely correlated with cardiovascular mortality in individuals without coronary symptoms at baseline. For example, among 2994 women aged 30 to 80 years followed for two decades in the Lipid Research Clinics Study, the risk for cardiovascular mortality decreased by 17% for every 1-MET increment in exercise capacity, after adjustment for multiple risk factors [28]. In an 8-year follow-up of 5636 women aged 35 years and older (the St James Women Take Heart Study), cardiac mortality declined by 22% for each 1-MET increase in exercise capacity, after adjustment for coronary risk profile [29]. A recent meta-analysis of data from 24 prospective cohorts with a total of 84,323 initially healthy participants (the majority were men) and 4485 CVD endpoints (many studies considered only cardiovascular mortality) found a significant 15% decline in cardiovascular risk for each 1-MET increase in exercise capacity [30]; the relation was similar in the 16 studies that included only men (risk reduction, 14%) and in the eight studies that included both sexes or only women (risk reduction, 16%). However, data on the relation between cardiorespiratory fitness and risk for nonfatal cardiovascular events in women are sparse. In modestly sized cohorts of relatively young women, researchers from the Aerobics Center Longitudinal Study [31] (5909 female participants, 82% of whom were younger than age 55) and Framingham Heart Study [32] (1612 female participants, average age of 45) reported suggestive but nonsignificant inverse relations between exercise capacity and incidence of (a) nonfatal CVD and (b) fatal plus nonfatal CHD, respectively, after adjustment for traditional coronary risk factors.
Protective mechanisms Weight control
Resistance exercise Although aerobic exercise has been the focus of most epidemiologic investigations of physical activity to date, there is growing recognition that resistance exercise may also reduce cardiovascular risk. In the Health Professionals Follow-up Study, men who trained with weights for at least 30 minutes per week were 23% less likely to develop CHD during an 8-year follow-up than men who did not train with weights [12]. Aerobic and resistance exercise also confer
Together with caloric intake, physical activity is a key determinant of energy balance and thus degree of adiposity. Obesity is an established cardiovascular risk factor; prospective studies in female populations indicate that an estimated 25% of CHD cases are attributable to excess weight and that each kilogram of weight gained during midlife increases CHD risk by 3% [33]. It is thus likely that one pathway by which physical activity attenuates cardiovascular risk is via regulation of body weight. Indeed,
Physical activity and cardiovascular disease prevention in women the Institute of Medicine highlighted the issue of weight control in its controversial 2002 recommendation espousing 60drather than 30dminutes per day of physical activity for weight maintenance and maximal health benefits [34]. From a public health perspective, this recommendation may not have made a clear enough distinction between the goal of weight control and the goal of disease risk reduction nor given enough attention to balancing efficacy and feasibility considerations [35,36]. Subsequently, while acknowledging that higher activity levels lead to greater cardiovascular risk reduction, the American Heart Association and American College of Sports Medicine reaffirmed the 30-minute guideline for prevention of CVD [2,3]. The latter organization recently reviewed the empirical literature on physical activity in relation to weight control and concluded that, in the absence of caloric restriction, 150e250 minutes per week of moderate-intensity activity appears to be effective for preventing weight gain but not for producing clinically significant weight loss, while more than 250 minutes per week of such activity appears to be necessary for clinically significant weight loss as well as for the prevention of weight gain following weight loss [37]. Although weight control is an important goal, focusing on it as the main reason for engaging in physical activity gives an incomplete assessment of exercise’s impact on cardiovascular health. With few exceptions, prospective observational studies find that inverse relations between physical activity and risk for CVD persist even after factoring out the effects of body mass index, suggesting that the cardiovascular benefits derived from physical activity are not solely attributable to weight regulation. Moreover, as shown in Fig. 2, data from the Nurses’ Health Study indicate that physical inactivity and obesity independently contribute to the development of CHD in initially healthy women [38]. Findings from other large cohorts are similar [39e41].
Other mechanisms Physical activity appears to slow the initiation and progression of CVD through beneficial effects not only on adiposity but also on insulin sensitivity, glycemic control,
471
Table 1 Proposed ‘‘Prescription’’.
elements
for
an
exercise
Take the stairs whenever possible. Purchase a pedometer and aim for 10,000 steps per day. Display ‘‘exercise prescription’’ in a visible place. If you drive to work or stores, park in a space far away from the door and walk. If you take public transportation, get off a stop early and walk. Walk on your lunch break. Try exercising with friends or a group. Add strength training for 20 minutes 2e3 times per week.
Source: Manson JE et al., Arch Intern Med 2004; 164:249e58. Copyright ª2004, American Medical Association. All rights reserved.
type 2 diabetes incidence, blood pressure, lipids, endothelial function, hemostasis, and inflammatory defense systems [42]. In the Women’s Health Study, these factors explained 59% of the observed inverse relation between physical activity and incident CVD over an 11-year followup period [43]. Inflammatory/hemostatic risk factors (C-reactive protein, fibrinogen, and soluble intercellular adhesion molecule-1) made the largest contribution to lower risk (32.5%), followed by blood pressure (27.1%), traditional lipids (19.1%), the novel lipids lipoprotein(a) and apolipoproteins A1 and B-100 (15.5%), body mass index (10.1%), and hemoglobin A1c/diabetes (8.9%). Findings from observational studies and randomized trials indicate that regular moderate-intensity activity is as effective as more vigorous activity in reducing blood pressure and improving insulin sensitivity [42]. (A recent randomized trial in patients with type 2 diabetes found that a combination of aerobic and resistance exercise yielded greater improvement in glycemic control than did either type of exercise alone [44].) In contrast, strong dose-response associations between exercise intensity and blood lipidsdspecifically, triglycerides and high-density lipoprotein cholesteroldhave been reported [42].
Conclusion 3.4
3.3
3.5
2.5
Relative risk*
3 2.5
2.0
1.9
2 1.5
1.4 1.5
1
30+
1.3
25 - 29.9 x (k e
1.0
0.5
<25
0
<1
1-3.5
3.5+
Physical activity (hours/week)
B
ym od
s as
2
m g/
)
ind
Figure 2 Relative risk for coronary heart disease according to body mass index and physical activity level, Nurses’ Health Study, 1980e2000. *Relative risks are adjusted for age, smoking status, alcohol consumption, menopausal status, postmenopausal hormone use, aspirin use, and parental history of CHD. Data from: Li TY et al., Circulation 2006;113:499e506.
Epidemiologic studies suggest that as little as 30 minutes per day of brisk walking or other moderate-intensity physical activity can reduce the incidence of clinical cardiovascular events in women. In a sedentary society such as the United States, a key challenge to clinicians and policymakers is identifying strategies to facilitate sustained physical activity at a level sufficient to result in measurable improvements in health. Based on our review of available scientific data, we believe that the clinical and public health message regarding exercise for CVD prevention should remain ‘‘30 minutes per day of moderate activity is beneficial, although more is better, to a reasonable extent.’’ Although more than 2 in 3 adults do not exercise enough to meet the 30-minute guideline, only 1 in 3 persons in the U.S. who saw a physician in the prior year received physical activity counseling at their last visit, according to National
472 Health Interview Survey data [45]. However, a survey of primary-care physicians in Canada found that 70% reported routinely counseling patients about physical activity [46]. Although the prevalence of clinician counseling remains unclear, failure to counsel is often attributed to lack of time, training, and appropriate patient materials, yet such counseling need not be time intensive or intricate. Data from the multi-center Activity Counseling Trial suggest that clinicians can easily learn to incorporate 3 to 4 minutes of physical activity advice into routine office visits [47] and that counseling can help sedentary patients become more active [48]. A simple blueprint for physicians who are perplexed about how to incorporate brief counseling about physical activity into their daily practices was published in a recent commentary [49]. Lay publications to help sedentary women and older individuals increase their activity level are available online at no charge from the American Heart Association [50], the National Institute on Aging [51], the National Heart, Lung and Blood Institute [52], and the U.S. Department of Health and Human Services [4]. Possible elements for an exercise ‘‘prescription’’ for patients are listed in Table 1. Data from randomized trials suggest that ‘‘lifestyle activity’’ interventions, which encourage individuals to incorporate short bouts of physical activity into their daily life (e.g., taking walks during lunch breaks, doing yard work or gardening, and using the stairs instead of the elevator), can be more effective than formal exercise programs in boosting activity levels and improving fitness and cardiovascular risk profiles [53]. The use of self-monitoring strategies such as pedometers or exercise diaries also promotes daily activity. In a meta-analysis of data from 26 studies (including 8 randomized trials) in which 85% of the participants were women, pedometer use led to a significant 27% increase in physical activity as well as significant reductions in body mass index and blood pressure [54]. More research on the characteristics of other individualand community-based interventions, initiatives, and policies that promote healthful exercise behaviors are needed [55]. Given the high prevalence of sedentary behavior, a widespread effort to help patients achieve even modest increases in regular physical activity will likely favorably influence cardiovascular morbidity and mortality. As the eminent British epidemiologist Geoffrey Rose has observed [56], the overall disease burden in a given population generally undergoes a more dramatic reduction when a large segment of the population adopts small improvements in health behaviors than when a small segment of the population adopts large improvements.
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