Adobe Flash Player is required to view this feature. If you are using an operating system that does not support Flash, we are working to bring you alternative formats. Original Article A Prospective Study of Walking as Compared with Vigorous Exercise in the Prevention of Coronary Heart Disease in Women JoAnn E. Manson, M.D., Dr.P.H., Frank B. Hu, M.D., Ph.D., Janet W. Rich-Edwards, Sc.D., Graham A.

Colditz, M.D., Dr.P.H., Meir J. Stampfer, M.D., Dr.P.H., Walter C. Willett, M.D., Dr.P.H., Frank E.

Speizer, M.D., and Charles H. Hennekens, M.D., Dr.P.H. N Engl J Med 1999; 341:650-658 DOI: 10.1056/NEJM10904. Methods We prospectively examined the associations between the score for total physical activity, walking, and vigorous exercise and the incidence of coronary events among 72,488 female nurses who were 40 to 65 years old in 1986. Participants were free of diagnosed cardiovascular disease or cancer at the time of entry and completed serial detailed questionnaires about physical activity. During eight years of follow-up, we documented 645 incident coronary events (nonfatal myocardial infarction or death from coronary disease). Results There was a strong, graded inverse association between physical activity and the risk of coronary events.

As compared with women in the lowest quintile group for energy expenditure (expressed as the metabolic-equivalent [MET] score), women in increasing quintile groups had age-adjusted relative risks of 0.77, 0.65, 0.54, and 0.46 for coronary events (P for trend. Figure 2 Age-Adjusted and Multivariate Relative Risks of Coronary Events (Nonfatal Myocardial Infarction or Death from Coronary Causes) According to Walking Pace.

These analyses excluded women who engaged in vigorous exercise. Multivariate relative risks have been adjusted for the variables in the full multivariate model, as listed in Tables 2 and 3, and for MET score for walking. Women who walked at an easy or casual pace served as the reference group. I bars indicate 95 percent confidence intervals.

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To convert miles per hour to kilometers per hour, multiply by 1.6. Figure 1 Multivariate Relative Risk of Coronary Events (Nonfatal Myocardial Infarction or Death from Coronary Causes) According to Quintile Group for Total Physical Activity within Subgroups Defined According to Smoking Status (Panel A), Body-Mass Index (Panel B), and Presence or Absence of a Parental History of Premature Myocardial Infarction (Panel C).

For each risk factor, the reference group is the category at highest risk. Relative risks have been adjusted for the variables in the full multivariate model (listed in Table 2). In epidemiologic studies, physical activity has been associated with a decrease in the risk of coronary heart disease, but data on women have been sparse.

Moreover, the specific role of walking, the most common form of exercise among women, has not been fully elucidated. The most recent federal guidelines from the Centers for Disease Control and Prevention and the American College of Sports Medicine, as well as the Surgeon General's report on physical activity and health, endorse at least 30 minutes of moderate-intensity physical activity on most, and preferably all, days of the week, whereas earlier guidelines recommended vigorous endurance exercise for at least 20 minutes three or more times per week. Although the current guidelines encourage a level of activity that is safe, achievable, and feasible for most Americans (60 percent of whom do not engage in regular physical activity), the potential benefits of moderate-intensity activity in preventing coronary heart disease remain unclear. We therefore assessed the comparative roles of walking and vigorous exercise in the prevention of coronary events in a large cohort of women enrolled in the prospective Nurses' Health Study. Detailed and repeated assessments of physical activity were performed to examine the degree to which total physical activity, walking time and pace, vigorous exercise, and change in activity level were associated with the incidence of coronary events in this cohort. Study Population The Nurses' Health Study was initiated in 1976, when 121,700 female registered nurses 30 to 55 years old who were residing in 11 large U.S.

States completed a mailed questionnaire on their medical history and lifestyle. Every two years, follow-up questionnaires have been sent to obtain updated information on potential risk factors and to identify newly diagnosed cases of coronary heart disease or other illnesses. For the primary analyses in the present study, the base-line data were those gathered in 1986, when detailed information on physical activity was first collected, and the duration of follow-up was eight years.

After women who reported a diagnosis of cardiovascular disease or cancer at base line were excluded, the population for analysis was made up of 72,488 women 40 to 65 years old in 1986. Assessment of Physical Activity Detailed information on physical activity was first collected in 1986 and was updated in 1988 and 1992. Participants were asked to report the average amount of time spent per week during the previous year in walking or hiking outdoors (including walking to work or while playing golf), jogging (at a speed slower than 10 minutes per mile [6 minutes per kilometer]), running (at 10 minutes per mile or faster), bicycling (including the use of a stationary bicycle), swimming laps, playing tennis or squash, or participating in calisthenics, aerobics, or aerobic dance; in addition, the women were asked to report the average number of flights of stairs they climbed each week. Women also reported their usual walking pace: easy or casual (.

Ascertainment of End Points The primary end points for this study were coronary events (defined as nonfatal myocardial infarction or death due to coronary disease) that occurred after the return of the 1986 questionnaire and before June 1994. We requested permission to review the medical records of women who reported a nonfatal myocardial infarction on a follow-up questionnaire. Study physicians who had no knowledge of the women's self-reported risk factors reviewed the records.

Nonfatal myocardial infarction was confirmed if data in the medical records met World Health Organization criteria for this condition — namely, symptoms and either diagnostic electrocardiographic changes or elevated cardiac-enzyme levels. Myocardial infarctions that required hospital admission and for which confirmatory information was obtained by interview or letter but for which no medical records were available were designated as probable infarctions (and constituted 17 percent of all reported nonfatal infarctions). We included all confirmed and probable cases of infarction in the analyses because the results were the same whether probable cases were included or excluded. Follow-up information for nonfatal infarction was obtained for more than 95 percent of the potential person-time of follow-up. Deaths were reported by family members or the Postal Service or were ascertained through state registries or the National Death Index. We estimate that follow-up for deaths was more than 98 percent complete. Fatal coronary disease (codes 410 through 414 of the International Classification of Diseases, 8th Revision ) was confirmed by review of the hospital or medical autopsy records or by review of the death certificate if coronary disease was the stated cause of death and evidence of previous coronary disease was available.

We designated deaths for which coronary disease was listed as the underlying cause on the death certificate, but for which no records were available, as due to presumed fatal coronary disease. These cases constituted 14.7 percent of all fatal coronary events. We also included sudden deaths (12.3 percent of all fatal coronary events). Analyses limited to confirmed cases yielded results similar to those in which confirmed and presumed cases of fatal coronary disease were combined. Statistical Analysis For primary analyses, we used the detailed assessment of physical activity performed in 1986 as the base line. Person-time for each participant was calculated from the date of her return of the 1986 questionnaire to the date of an incident coronary event, death from any cause, or June 1, 1994, whichever came first.

Data on women who had a coronary event or who died from any cause were censored with respect to subsequent analysis during follow-up. The relative risk of a coronary event was computed as the incidence of the event in each quintile group for MET score, divided by the incidence in the lowest quintile group, with adjustment for five-year age categories. Tests of linear trend for increasing quintiles of MET scores were performed by treating the score as a continuous variable and designating the median score for the category as its value.

To represent long-term levels of physical activity for individual women as accurately as possible and to reduce measurement error, we calculated cumulative averages of the MET scores from all the questionnaires available up to the start of each two-year follow-up interval. A similar method for analyzing repeated dietary measurements has been described in detail elsewhere. For secondary analyses, we used data gathered in 1980 as the base line.

We used the continuous values of hours of activity per week to compute the cumulative averages at the start of each interval and grouped the average hours per week of moderate or vigorous exercise into five categories (. Results The distribution at base line of several indicators of coronary risk varied according to quintile group for total physical-activity score (expressed as MET-hours per week) in this cohort ( Table 1 Distribution of Indicators of Coronary Risk According to Quintile Group for Total Physical-Activity Score at Base Line (1986). Women who were more physically active were less likely to be current smokers and, as expected, were leaner and had a lower prevalence of reported hypertension, diabetes, and hypercholesterolemia than less active women. More physically active women were also more likely to use postmenopausal hormone-replacement therapy, multivitamin and vitamin E supplements, and alcohol. In contrast, the activity level was not appreciably related to age, parental history of myocardial infarction, or dietary intake of fats or cholesterol. The eight years of follow-up, from 1986 to 1994, included 559,435 person-years.

During this follow-up period we documented 645 coronary events (475 nonfatal myocardial infarctions and 170 deaths from coronary disease) among the 72,488 women who in 1986 were 40 to 65 years old, had neither cardiovascular disease nor cancer, and completed a detailed physical-activity questionnaire. The total physical-activity score (expressed as MET-hours per week) in 1986 was strongly inversely related to the risk of coronary events during the eight-year follow-up ( Table 2 Relative Risk of Coronary Events According to Quintile Group for Total Physical-Activity Score. In age-adjusted analyses from 1986 to 1994 (in which MET scores, first computed in 1986, were calculated as cumulative updated averages in 1988 and 1992), the risk of coronary events decreased monotonically with increasing quintiles for MET score (relative risks, 0.77, 0.65, 0.54, and 0.46 as compared with the risk in the lowest quintile group; P for trend. Discussion These prospective data from a large cohort of women indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of coronary events.

We observed that in this cohort, the magnitudes of risk reduction associated with brisk walking and vigorous exercise were similar when total energy expenditures were similar. These findings lend further support to current federal exercise guidelines, which endorse moderate-intensity exercise for at least 30 minutes on most (preferably all) days of the week.

Our results suggest that such a regimen (e.g., brisk walking for three or more hours per week) could reduce the risk of coronary events in women by 30 to 40 percent. Increasing walking time or combining walking with vigorous exercise appears to be associated with even greater risk reductions.

Given the high prevalence in the United States of a sedentary lifestyle (78 percent of adults engage in less physical activity than currently recommended), we estimate, on the basis of our multivariate relative-risk analyses, that one third of coronary events among middle-aged women in the United States are attributable to physical inactivity. The strengths of the current study include the prospective design, the large size of the cohort, the long-term follow-up, repeated measures of physical activity, and the uniform and strict criteria for coronary events. Women with diagnosed cardiovascular disease or cancer at base line were excluded from the analyses. These exclusions and the prospective design minimized any influence that underlying disease may have had on physical-activity levels and decreased the potential for biased reporting of activity. Moreover, in our secondary analyses, the first two years of follow-up were excluded in order to minimize bias related to subclinical disease. The repeated measures of physical activity enabled us to calculate more stable, cumulative, and updated classifications of activity status as well as to assess the role of changes in activity level over time. Other advantages include the level of detail of information gathered about walking time and pace on the survey first administered in 1986, the high rate of participation during follow-up, and the collection of information about a large number of potential confounders, including cigarette smoking, body-mass index, family history of myocardial infarction, postmenopausal hormone use, alcohol consumption, diet, and other coronary risk factors.

The substantial reduction in the risk of coronary events among women who increased their activity level, as compared with women who remained sedentary, and the strong dose–response gradient observed in each analysis lend credence to the interpretation that there is a causal relation between physical activity and a reduced risk of coronary events and that the risk may be modified through increased activity, even when it is begun in later adulthood. Because our multivariate analyses controlled for several factors that could be considered intermediate biologic variables (such as body-mass index and a history of hypertension, hypercholesterolemia, or diabetes), the analyses provide a conservative estimate of the relation between physical activity and coronary disease. In analyses that excluded these biologic intermediates, the inverse association between physical activity and coronary events was strengthened ( ).

Limitations of the current study must also be considered. Physical activity was assessed by a self-administered questionnaire and, despite the use of repeated measures, there was undoubtedly some misclassification. However, in a validation study, conducted in a separate cohort of nurses, the correlations between physical activity as reported on the questionnaire and as recorded in four one-week diaries or recalled after one week were reasonably high (r=0.62 and r=0.79, respectively). Random misclassifications would be expected to lead to underestimation of the true association and to bias the estimate of risk toward unity; therefore, misclassification cannot explain the strong inverse associations in our cohort between physical-activity level and the incidence of coronary events. Nevertheless, despite the control for many potential confounding variables in our multivariate analyses, residual confounding by lifestyle factors cannot be excluded. In this regard, it should be noted ( ) that the more active women had more favorable risk profiles. Finally, our study population, consisting of registered nurses, is not representative of the general population.

The relative homogeneity of the cohort in educational attainment and socioeconomic status may actually serve to enhance the internal validity of this study; confounding by these factors has posed an important problem in many previous studies of physical activity and coronary disease. More than 40 epidemiologic studies have addressed the relation between exercise and coronary disease, but few have included women and presented data on women separately. In those that did, results in women were generally similar to those in men, indicating that risk reductions were 30 to 50 percent in both sexes with regular physical activity. Most of these studies were small, however, and did not collect detailed information about walking or report repeated measures of activity. The evidence that moderate-intensity activity is associated with a reduction in the risk of coronary disease, however, has been mounting. In a recent report from the Iowa Women's Health Study, both moderate activity and vigorous activity were inversely related to overall mortality and mortality due to cardiovascular causes, although walking was not assessed separately. In two recent studies among elderly women and men, walking at least four hours per week was associated with substantial reductions in cardiovascular risk.

Even moderate levels of physical fitness (assessed by treadmill testing) have been associated with substantial reductions in mortality due to cardiovascular events and in total mortality. It is unlikely that genetic and constitutional differences in fitness levels and in the ability to exercise explain these findings: in a study of nearly 16,000 men and women in the Finnish Twin Cohort, leisure-time physical activity was associated with reduced mortality, even after the analyses had accounted for genetic, familial, and behavioral factors. It is also biologically plausible that both moderate exercise and vigorous exercise have an important role in reducing coronary risk. Increasing the intensity or duration of exercise has a graded relation to improvements in lipid concentrations and insulin sensitivity. Randomized trials of the effects of different intensities of exercise on blood pressure suggest that moderate- and vigorous-intensity activity may confer similar reductions in diastolic blood pressure and that moderate-intensity activity may confer even greater reductions in systolic blood pressure than vigorous-intensity exercise.

In the Insulin Resistance Atherosclerosis Study, both vigorous and nonvigorous levels of physical activity were directly associated with insulin sensitivity. Moreover, equivalent expenditures of energy in moderate or vigorous exercise will lead to similar reductions in adipose mass. A recent study indicated that moderate-intensity exercise reduces the secretion of atherogenic cytokines. Finally, physical activity of all intensities has been linked to improvement in emotional well-being and reduction in anxiety and stress. In conclusion, these prospective data from a study of a large cohort of women indicate that both walking and vigorous exercise are associated with substantial reductions in the risk of coronary events.

We observed a strong, graded inverse relation between energy expenditure in either walking or vigorous activity and the incidence of coronary disease. Among women who either walked briskly at least 3 hours per week or exercised vigorously for 1.5 hours per week, the risk was reduced by 30 to 40 percent. These findings lend support to current federal guidelines that endorse moderate-intensity exercise, which is safe, achievable, and feasible for the majority of the population. Although vigorous exercise should not be discouraged for those who choose a higher intensity of activity, our results indicate that enormous public health benefits would accrue from the adoption of regular moderate-intensity exercise by those who are currently sedentary. Source Information From the Channing Laboratory (J.E.M., G.A.C., M.J.S., W.C.W., F.E.S.) and the Division of Preventive Medicine (J.E.M., C.H.H.), Department of Medicine, Harvard Medical School and Brigham and Women's Hospital; the Departments of Nutrition (F.B.H., M.J.S., W.C.W.) and Epidemiology (J.E.M., G.A.C., M.J.S., W.C.W., C.H.H.), Harvard School of Public Health; and the Department of Ambulatory Care and Prevention, Harvard Medical School (J.W.R.-E., C.H.H.) — all in Boston. Address reprint requests to Dr. Manson at Brigham and Women's Hospital, 181 Longwood Ave., Boston, MA 02115,.

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