Walking Compared with Vigorous Exercise for the Prevention of Cardiovascular Events in Women
JoAnn E. Manson, M.D., Dr.P.H., Philip Greenland, M.D., Andrea Z. LaCroix, Ph.D., Marcia L. Stefanick, Ph.D., Charles P. Mouton, M.D., Albert Oberman, M.D., M.P.H., Michael G. Perri, Ph.D., David S. Sheps, M.D., Mary B. Pettinger, M.S., and David S. Siscovick, M.D., M.P.H.
Background The role of walking, as compared with vigorous exercise,in the prevention of cardiovascular disease remains controversial.Data for women who are members of minority racial or ethnicgroups are particularly sparse.
Methods We prospectively examined the total physical-activityscore, walking, vigorous exercise, and hours spent sitting aspredictors of the incidence of coronary events and total cardiovascularevents among 73,743 postmenopausal women 50 to 79 years of agein the Women's Health Initiative Observational Study. At baseline, participants were free of diagnosed cardiovascular diseaseand cancer, and all participants completed detailed questionnairesabout physical activity. We documented 345 newly diagnosed casesof coronary heart disease and 1551 total cardiovascular events.
Results An increasing physical-activity score had a strong,graded, inverse association with the risk of both coronary eventsand total cardiovascular events. There were similar findings among white women and black women.Women in increasing quintilesof energy expenditure measured in metabolic equivalents (theMET score) had age-adjusted relative risks of coronary eventsof 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend,<0.001). In multivariate analyses, the inverse gradient betweenthe total MET score and the risk of cardiovascular events remainedstrong (adjusted relative risks for increasing quintiles, 1.00,0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001).Walking and vigorous exercise were associated with similar riskreductions, and the results did not vary substantially accordingto race, age, or body-mass index. A brisker walking pace andfewer hours spent sitting daily also predicted lower risk.
Conclusions These prospective data indicate that both walkingand vigorous exercise are associated with substantial reductionsin the incidence of cardiovascular events among postmenopausalwomen, irrespective of race or ethnic group, age, and body-massindex. Prolonged sitting predicts increased cardiovascular risk.
Physical activity has been associated with a reduced risk ofcardiovascular disease in epidemiologic studies,1,2 but datafor women and members of minority ethnic groups have been sparse.Moreover, the specific role of walking, the most common formof exercise among women,3 has been addressed only minimally.Federal guidelines from the Centers for Disease Control andPrevention and the American College of Sports Medicine,4 aswell as the Surgeon General's Report on Physical Activity andHealth,3 endorse at least 30 minutes of moderate-intensity physicalactivity on most, and preferably all, days of the week, in contrastto earlier guidelines that recommended vigorous endurance exercisefor at least 20 minutes three or more times per week.5 Althoughthe federal guidelines encourage a level of activity that issafe, accessible, and feasible for most Americans6(at least75 percent of whom have less than the recommended level of activity3),the potential benefits of moderate-intensity activity in preventingcardiovascular events remain uncertain. Moreover, the role oftime spent in sedentary behavior, such as sitting, in predictingrisk remains relatively unexplored.
We therefore compared the roles of walking and vigorous exercisein the prevention of coronary and cardiovascular events in alarge, ethnically diverse cohort of postmenopausal women. Usingdetailed assessments of physical activity, we examined the magnitudeof associations between each of the measures of physical activity(the total physical-activity score, the intensity of exercise[walking vs. vigorous exercise], and the hours spent sitting)and the incidence of cardiovascular events.
Methods
Study Population
The study population consisted of 73,743 women who were enrolledin the Women's Health Initiative Observational Study, whichinvolved a national, multicenter cohort of postmenopausal womenwho were 50 to 79 years of age at entry. The Women's HealthInitiative is a prospective, ethnically and racially diverse,multicenter clinical trial and observational study designedto address the major causes of illness and death in postmenopausalwomen (see the Appendix for a list of study investigators).A total of 93,676 women were enrolled in the observational studyat 40 clinical centers between 1994 and 1998. Criteria for exclusionfrom the study included the presence of any medical conditionassociated with predicted survival of less than three years(e.g., class IV congestive heart failure, obstructive lung diseaserequiring supplemental oxygen, or severe chronic liver or kidneydisease), alcoholism, mental illness, or dementia. In addition,women were excluded from the present analyses if, at base line,they had a history of coronary heart disease, stroke, or cancer;were nonambulatory (unable to walk at least one block); or hadmissing data on the physical-activity questionnaire. After womenhad been excluded for these reasons, 73,743 women remained inthe analysis. Of these women, 61,574 were non-Hispanic white,5661 were non-Hispanic black, 2880 were Hispanic, 2288 wereAsian or Pacific Islander, and 1340 were American Indian orof other racial or ethnic background. Race was self-assigned.Details of the scientific rationale, design, eligibility requirements,and base-line characteristics of the cohort have been publishedelsewhere.7
Exposure Assessment
All women enrolled in the Observational Study were requiredto come for a clinic visit for base-line screening. At thisvisit, women completed self-administered questionnaires relatedto personal and family medical history, physical activity, smoking,diet, and other behavioral and lifestyle-related factors. Clinicalmeasurements including height, weight, waist and hip circumferences,and blood pressure were obtained by trained staff members. Allwomen provided written informed consent, and the study protocolwas approved by the institutional review board of each center.
Recreational physical activity was assessed by a detailed questionnaireon the frequency and duration of walking and of several othertypes of activity (strenuous, moderate, and mild). Walking wasassessed by a series of questions about the frequency of walksoutside the home for more than 10 minutes without stopping,the average duration of each walk, and the usual walking pace.Vigorous exercise was defined as that in which "you work upa sweat and your heart beats fast," and examples included aerobics,aerobic dancing, jogging, tennis, and swimming laps. Moderateexercise was defined as that which was "not exhausting," andexamples included biking outdoors, using an exercise machine(such as a stationary bicycle or a treadmill), calisthenics,easy swimming, and popular or folk dancing. Examples of mildexercise were slow dancing, bowling, and golf. Using a standardizedclassification of the energy expenditure associated with physicalactivities,8 we calculated a weekly energy-expenditure scorein metabolic equivalents (MET score) for walking and for totalphysical activity. Finally, participants were asked to estimatethe number of hours per day they spent engaged in sedentarybehavior, including time spent sitting as well as lying downor sleeping.
Reproducibility and Validation of the Physical-Activity Assessment
A sample of participants in the Observational Study (1092 women)was recruited into a reliability study to assess the reproducibilityof selected questionnaires, including the physical-activityassessment. The average time between base line and repeatedassessments was three months. The test–retest reliabilityfor recreational physical activity, including walking and strenuousactivity, was assessed (weighted kappas among all women rangedfrom 0.67 to 0.71).7 The intraclass correlation coefficientfor the primary summary variable (total energy expenditure inMET from all recreational physical activity) was 0.77. A similarphysical-activity questionnaire has been found to be correlatedwith physical-activity diaries (r=0.62) and with one-week recallof activity (r=0.79) in a cohort of female health professionals.9
Ascertainment of End Points
The primary end points for this study were newly diagnosed coronaryheart disease (nonfatal myocardial infarction or death fromcoronary causes) and total cardiovascular events (myocardialinfarction, death from coronary causes, coronary revascularization,angina, congestive heart failure, stroke, or carotid revascularization)that occurred after the return of the base-line questionnairebut before August 27, 2000. Newly diagnosed cardiovascular eventswere identified on the basis of annual mailed follow-up questionnaires(response rates have been above 95 percent), and permissionto review medical records was requested. Study physicians withno knowledge of the self-reported risk-factor status reviewedthe records. The diagnosis of nonfatal myocardial infarctionwas confirmed if data in the hospital record met standardizedcriteria of diagnostic electrocardiographic changes, elevatedcardiac-enzyme levels, or both.10 Treatment with coronary orcarotid revascularization was confirmed by documentation ofthe procedure in the medical record. The presence of anginawas confirmed by hospitalization and confirmatory evidence onangiography, diagnostic stress test, or diagnosis by a physicianand medical treatment. The occurrence of stroke was confirmedby documentation in the medical record of the rapid onset ofa neurologic deficit consistent with stroke and lasting at least24 hours or until death. The presence of congestive heart failurewas confirmed by hospitalization and diagnostic confirmatorytests.
Fatal coronary disease was considered confirmed if there wasdocumentation in the hospital or autopsy records or if coronarydisease was listed as the cause of death on the death certificateand evidence of previous coronary disease was available. Fordeaths from other cardiovascular causes, a review of confirmatoryevidence by physician-adjudicators was required.
Statistical Analysis
Our primary analyses used the detailed physical-activity assessmentat base line. Person-time for each woman was calculated fromthe date of return of the base-line questionnaire to the dateof a confirmed cardiovascular event, death from any cause, orAugust 27, 2000, whichever came first. Age-adjusted relativerisks were computed as the incidence rate in a specific categoryof activity divided by the incidence rate in the lowest quintile,with adjustment for one-year age categories. We conducted testsof linear trend by treating the categories as a continuous variableand assigning the median score for each category.11 All testsof statistical significance were two-sided.
We used Cox proportional-hazards regression12 to adjust simultaneouslyfor potential confounding variables, including age, smokingstatus, body-mass index (the weight in kilograms divided bythe square of the height in meters), the ratio of the waistcircumference to the hip circumference, alcohol consumption,age at menopause, use of hormone-replacement therapy, parentalhistory of premature myocardial infarction (before 55 yearsof age in the father or before 65 years of age in the mother),race or ethnic group, education, family income, and severaldietary variables. Additional models controlled for historyor absence of history of hypertension, diabetes, and high cholesterollevels, as well as for functional status and a summary scorefor mental and emotional health.13 The total MET score, theMET score for walking, time spent in vigorous exercise, walkingpace, and hours spent sitting and lying down or sleeping wereanalyzed separately. Differences in the results for activityaccording to race (white women vs. black women), age, and body-massindex were assessed. Secondary analyses excluded data for thefirst year of follow-up in order to minimize potential biascaused by the presence of subclinical disease.
Results
During up to 5.9 years of follow-up (mean, 3.2 years; total,232,971 person-years), we documented 345 newly diagnosed casesof coronary disease (287 nonfatal myocardial infarctions and58 deaths from coronary causes), 309 strokes, and 1551 firstcardiovascular events among the 73,743 women 50 to 79 yearsof age who completed a detailed physical-activity questionnaire,were ambulatory, and were free of cardiovascular disease andcancer at base line. The base-line characteristics of the cohortand the distribution of physical-activity profiles and otherrisk factors have been described elsewhere.7
The total physical-activity score (in MET-hours per week) atbase line had a strong inverse relation with the risk of coronaryheart disease during the follow-up period (Table 1). In age-adjustedanalyses, the relative risk declined with increasing quintilesof the total MET score (1.00, 0.73, 0.69, 0.68, and 0.47, respectively;P for trend <0.001). Risk reductions for increasing categoriesof walking (P for trend = 0.004) were similar to those for increasingcategories of vigorous exercise (activities with MET scoresof 6 or higher; P for trend = 0.008) (Table 1).
Table 1. Relative Risks of Cardiovascular Disease According to Quintile of Total Physical-Activity Score and Categories of Walking and Vigorous Exercise.
Reductions in the risk of total cardiovascular events with increasingcategories of total MET scores, walking, and vigorous exercisewere similar to those for the risk of coronary disease (Table 1).Women who either walked or exercised vigorously at least2.5 hours per week had a risk reduction of approximately 30percent. Similar reductions in the risk of cardiovascular eventswith an increasing MET score were observed for white women andfor black women (for other racial and ethnic groups, the sampleswere not large enough to be analyzed separately), as well asfor women in different categories of age or body-mass index(Figure 1). The relative risk of cardiovascular disease in thehighest quintile of MET score as compared with the lowest quintilewas 0.55 (95 percent confidence interval, 0.47 to 0.65) amongwhite women and 0.48 (95 percent confidence interval, 0.25 to0.93) among black women. Moreover, increasing categories ofwalking were inversely associated with the risk of cardiovascularevents in each of these subgroups (Figure 2). Women who engagedin both walking and vigorous exercise had greater reductionsin cardiovascular risk than those who did either one alone (theage-adjusted relative risk for those in the highest categoryof each was 0.37 [95 percent confidence interval, 0.25 to 0.57])(Figure 3).
Figure 1. Age-Adjusted Relative Risks of Cardiovascular Disease According to Quintile of Total MET Score in Subgroups Defined by Race, Age, and Body-Mass Index (BMI).
The reference category is the lowest quintile of MET score.
Figure 2. Age-Adjusted Relative Risks of Cardiovascular Disease According to Energy Expenditure from Walking (MET-Hr/Wk) in Subgroups Defined by Race, Age, and Body-Mass Index (BMI).
The reference category is the lowest category of energy expenditure from walking.
Figure 3. Joint Association of Walking and Vigorous Exercise with the Age-Adjusted Relative Risk of Cardiovascular Disease.
RR denotes relative risk.
In multivariate analyses, after simultaneous control for age,race or ethnic group, smoking status, body-mass index, waist-to-hipratio, socioeconomic status, several dietary factors, and othercovariates, physical activity remained a powerful predictorof the subsequent risk of cardiovascular events (Table 1). Forincreasing quintiles of the total MET score, the relative riskswere 1.00, 0.89, 0.81, 0.78, and 0.72, respectively (P for trend<0.001). Increasing categories of walking were associatedwith similar reductions in risk (relative risks, 1.00, 0.91,0.82, 0.75, and 0.68, respectively; P for trend <0.001),which were also similar to the risk reductions with vigorousexercise (Table 1) and remained unchanged after simultaneousinclusion of walking and vigorous exercise in the model. Theseresults were not substantially altered after further controlfor biologic variables that could be considered to be in thecausal pathway, such as hypertension, hypercholesterolemia,and diabetes, and for the summary score for mental and emotionalhealth13 (the relative risks of cardiovascular events with increasingtotal MET scores were 1.00, 0.92, 0.87, 0.83, and 0.77, respectively;P for trend = 0.008). When we excluded data from the first yearof follow-up (to minimize potential bias caused by the influenceof subclinical disease on the activity level), the results werenot materially altered (the multivariate relative risk of cardiovasculardisease for women in the highest quintile of total MET scorewas 0.76 [95 percent confidence interval, 0.61 to 0.96; P fortrend = 0.02]).
Figure 4. Multivariate Relative Risk of Cardiovascular Disease and Relative Risk Adjusted for Age and Walking Time, According to Walking Pace.
Multivariate relative risks were adjusted for age, time spent walking, smoking status (0, 1 to 14, 15 to 24, or 25 cigarettes per day), race or ethnic group, level of education, annual family income, body-mass index, waist-to-hip ratio, level of alcohol intake, parental history of premature myocardial infarction, age at menopause, use or nonuse of hormone-replacement therapy, percentage of calories from saturated fat, number of servings of fruit and vegetables per day, and dietary fiber intake. To convert values for distance to kilometers, multiply by 1.6.
Finally, we assessed the relation between hours spent sitting,as well as hours spent lying down or sleeping, and the riskof cardiovascular events. After we accounted for age and recreationalenergy expenditure (total MET score), the relative risk of cardiovasculardisease was 1.38 (95 percent confidence interval, 1.01 to 1.87)among women who spent 12 to 15 hours per day lying down or sleepingand 1.68 (95 percent confidence interval, 1.07 to 2.64) amongwomen who spent at least 16 hours per day sitting, as comparedwith those who spent less than 4 hours per day. Other durationsof sitting or lying down were not significantly associated withcardiovascular risk.
Strengths of the present study include the prospective design,the large size, the racial and ethnic diversity of the cohort,the detailed assessment of physical activity as well as sedentarybehavior, and the uniform and strict criteria for the coronaryand cardiovascular end points. Women with diagnosed cardiovasculardisease or cancer at base line and those who were nonambulatory(unable to walk at least one block) were excluded from the analyses.These exclusions and the prospective design minimized any influenceof preexisting disease on the level of physical activity. Moreover,we performed secondary analyses excluding data from the firstyear of follow-up in order to minimize bias related to the presenceof subclinical disease. The strong dose–response gradientobserved between the physical-activity level and the reducedrisk of cardiovascular disease and the consistency of the findingsacross strata of age, race, and body-mass index lend furthercredence to a causal interpretation. Other strengths of thestudy include the high follow-up rate and the detailed informationabout potential confounding variables.
Some limitations of our study also deserve attention. Physicalactivity was assessed by questionnaire, and some misclassificationof exposure was inevitable. Nondifferential misclassificationof exposure, however, would be expected to bias the risk estimatetoward unity; thus, it cannot explain the strong inverse associationsobserved between the level of physical activity and the incidenceof cardiovascular events. Despite the fact that we controlledfor a large number of potentially confounding variables in ourmultivariate analyses, residual confounding by lifestyle-relatedfactors cannot be excluded. Finally, our study population ofvolunteers in the Women's Health Initiative, although of morediverse racial and ethnic background and socioeconomic statusthan most previously studied cohorts, is not an entirely representativecross-section of women in the United States.
More than 40 epidemiologic studies have addressed the relationbetween exercise and cardiovascular disease,1,2 but only onethird of published studies have included women,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28and few of these have specifically addressed the role of walking.14,15,16,17,18,19In previous studies, results for women have been generally similarto those for men, indicating that risk among both sexes is reducedby 30 to 50 percent with regular physical activity. Recent reportsfrom several large-scale cohort studies involving women14,15,20have suggested that moderate and vigorous exercise have similarcardiovascular benefits, but these cohorts were predominantlywhite. Moreover, to our knowledge, no previous large-scale studyhas addressed the relation between walking and cardiovascularevents in black women or the role of sitting after accountingfor recreational energy expenditure in women. The evidence thatmoderate-intensity activity is associated with a similar magnitudeof reduction in cardiovascular risk among white women and blackwomen, among younger and older postmenopausal women, and acrossthe spectrum of adiposity is important for the targeting ofthese diverse groups with health-promotion activities. The cardiovascularbenefits of walking29 and even moderate levels of physical fitness27,30also appear to apply to men.
An important role for both moderate and vigorous exercise inreducing cardiovascular risk is also biologically plausible.Increasing intensity or duration of exercise has a graded relationto improvements in lipid levels3,31 and insulin sensitivity.32Moderate-intensity activity may produce reductions in diastolicblood pressure similar to those achieved with vigorous exerciseand may produce even greater reductions in systolic blood pressure.3Moderate exercise coupled with modification of the diet ledto a reduced risk of type 2 diabetes among subjects with impairedglucose tolerance.33,34 Moreover, equivalent energy expenditurewith moderate or vigorous exercise leads to similar reductionsin adipose mass.3 Finally, physical activity of any intensityhas been linked to improvement in emotional well-being.3
Supported by the National Heart, Lung, and Blood Institute anda research contract (N01-WH-3-2109) from the National Institutesof Health.
We are indebted to the participants, investigators, and staffof the Women's Health Initiative for their outstanding dedicationand commitment and to Philomena Quinn for her expert assistance.
Source Information
From the Division of Preventive Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston (J.E.M.); the Department of Preventive Medicine, Northwestern University Medical School, Chicago (P.G.); the Fred Hutchinson Cancer Research Center (A.Z.L., M.B.P.) and the Departments of Medicine and Epidemiology (D.S.S.), University of Washington, Seattle; Stanford Center for Research in Disease Prevention, Stanford, Calif. (M.L.S.); the University of Texas Health Science Center, San Antonio (C.P.M.); the Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham (A.O.); and the Department of Clinical and Health Psychology (M.G.P.) and Division of Cardiology (D.S.S.), University of Florida, Gainesville.
Address reprint requests to Dr. Manson at the Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston, MA 02215, or at jmanson{at}rics.bwh.harvard.edu.
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Appendix
The following persons are members of the Women's Health InitiativeStudy Group. Program office: J.E. Rossouw, L. Pottern, S. Ludlam,J. McGowan, N. Morris (National Heart, Lung, and Blood Institute,Bethesda, Md.). Clinical coordinating center: R. Prentice, G.Anderson, A. LaCroix, R. Patterson, A. McTiernan (Fred HutchinsonCancer Research Center, Seattle); S. Shumaker, P. Rautaharju(Bowman Gray School of Medicine, Winston-Salem, N.C.); E. Stein(Medical Research Labs, Highland Heights, Ky.); S. Cummings(University of California at San Francisco, San Francisco);J. Himes (University of Minnesota, Minneapolis); S. Heckbert(University of Washington, Seattle). Clinical centers: S. Wassertheil-Smoller(Albert Einstein College of Medicine, Bronx, N.Y.); J. Hays(Baylor College of Medicine, Houston); J. Manson (Brigham andWomen's Hospital and Harvard Medical School, Boston); A.R. Assaf(Brown University, Providence, R.I.); L. Phillips (Emory University,Atlanta); S. Beresford (Fred Hutchinson Cancer Research Center,Seattle); J. Hsia (George Washington University Medical Center,Washington, D.C.); C. Ritenbaugh (Kaiser Permanente Center forHealth Research, Portland, Oreg.); B. Caan (Kaiser PermanenteDivision of Research, Oakland, Calif.); J. Morley Kotchen (MedicalCollege of Wisconsin, Milwaukee); B.V. Howard (Medstar ResearchInstitute, Washington, D.C.); L. Van Horn (Northwestern University,Chicago and Evanston, Ill.); H. Black (Rush–Presbyterian–St.Luke's Medical Center, Chicago); M.L. Stefanick (Stanford Centerfor Research in Disease Prevention, Stanford University, Stanford,Calif.); D. Lane (State University of New York at Stony Brook,Stony Brook); R. Jackson (Ohio State University, Columbus);C.B. Lewis (University of Alabama at Birmingham, Birmingham);T. Bassford (University of Arizona, Tucson and Phoenix); M.Trevisan (State University of New York at Buffalo, Buffalo);J. Robbins (University of California at Davis, Sacramento);A. Hubbell (University of California at Irvine, Orange); H.Judd (University of California at Los Angeles, Los Angeles);R.D. Langer (University of California at San Diego, LaJollaand Chula Vista); M. Gass (University of Cincinnati, Cincinnati);M. Limacher (University of Florida, Gainesville and Jacksonville);D. Curb (University of Hawaii, Honolulu); R. Wallace (Universityof Iowa, Iowa City and Davenport); J. Ockene (University ofMassachusetts, Worcester); N. Lasser (University of Medicineand Dentistry of New Jersey, Newark); M.J. O'Sullivan (Universityof Miami, Miami); K. Margolis (University of Minnesota, Minneapolis);R. Brunner (University of Nevada, Reno); G. Heiss (Universityof North Carolina, Chapel Hill); L. Kuller (University of Pittsburgh,Pittsburgh); K.C. Johnson (University of Tennessee, Memphis);R. Schenken (University of Texas Health Science Center, SanAntonio); C. Allen (University of Wisconsin, Madison); G. Burke(Wake Forest University School of Medicine, Winston-Salem, N.C.);S. Hendrix (Wayne State University School of Medicine and HutzelHospital, Detroit).
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Previous
25 cigarettes per day), race or ethnic group, level of education, annual family income, body-mass index, waist-to-hip ratio, level of alcohol intake, parental history of premature myocardial infarction, age at menopause, use or nonuse of hormone-replacement therapy, percentage of calories from saturated fat, number of servings of fruit and vegetables per day, and dietary fiber intake. To convert values for distance to kilometers, multiply by 1.6.