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I-Min Lee and Ralph S. Paffenbarger, JrPhysical Activity and Stroke Incidence: The Harvard Alumni Health Study

Print ISSN: 0039-2499. Online ISSN: 1524-4628Copyright 1998 American Heart Association, Inc. All rights reserved.is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231

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Physical Activity and Stroke IncidenceThe Harvard Alumni Health Study

I-Min Lee, MBBS, ScD; Ralph S. Paffenbarger, Jr, MD, DrPH

Background and PurposePhysiologically, it appears plausible for physical activity to decrease stroke risk; however,

epidemiological studies have produced mixed findings. Furthermore, few studies have examined specific kinds and

intensities of activities. The purpose of this study was to examine the association between physical activity, including

its various components (walking, climbing stairs, participation in sports and recreational activities), and stroke risk.

MethodsThis was a prospective cohort study of 11 130 Harvard University alumni (mean age, 58 years) without

cardiovascular disease and cancer at baseline. Men reported their walking, stair climbing, and participation in sports or

recreation on baseline questionnaires in 1977. Stroke occurrence was assessed with another questionnaire in 1988. Death

certificates were obtained for decedents through 1990 to determine strokes not previously reported (total strokes378).

We used Cox proportional hazards regression to estimate the relative risks and 95% CIs for stroke occurrence associated

with physical activity.

ResultsAfter adjustment for age, smoking, alcohol intake, and early parental death, the relative risks of stroke associated

with 1000, 1000 to 1999, 2000 to 2999, 3000 to 3999, and 4000 kcal/wk of energy expenditure at baseline were 1.00

(referent), 0.76 (95% CI, 0.59 to 0.98), 0.54 (0.38 to 0.76), 0.78 (0.53 to 1.15), and 0.82 (0.58 to 1.14), respectively;

P0.05 for linear trend. Walking 20 km/wk was associated with significantly lower risk, independent of other

physical activity components. Climbing stairs and activities of at least moderate intensity (4.5 METs, or multiples of

resting metabolic rate) each showed U-shaped relations to stroke risk, with the risk being significantly lower at the nadir

of the curve. Light intensity activities (4.5 METs), however, were unrelated to stroke risk.

ConclusionsPhysical activity is associated with decreased stroke risk in men. A decreased risk was observed at energy

expenditures of 1000 to 1999 kcal/wk, with further risk decrement seen at 2000 to 2999 kcal/wk but not beyond.

Confirmation of the U-shaped relation observed in these data requires similar observations in other populations.(Stroke.

1998;29:2049-2054.)

Key Words: epidemiology exercise risk factors stroke prevention

S troke ranks as the third leading cause of death in theUnited States, following coronary heart disease andcancer.1 Every year, 150 000 persons die from this disease,

while many more are disabled.1 It primarily afflicts older

individuals:130 000 of the 150 000 stroke deaths each year

occur among those aged 65 years.1 Currently, there is

limited treatment for most types of stroke. Thus, its preven-

tion is of public health importance. Two major causes of

stroke are atherosclerosis of intracranial or extracranial ves-

sels and high blood pressure.2 Therefore, in searching for

prevention strategies, physical activity is promising because it

has beneficial effects on the atherosclerotic process andreduces blood pressure.3,4 Several studies indeed show that

physical activity is associated with lower stroke risk517;

however, other studies do not support this hypothesis. 1824 In

fact, the Surgeon Generals report on physical activity and

health concluded that it is unclear whether physical activity

plays a protective role against stroke.25

To provide further information, we examined data from an

ongoing study of college alumni. Previous investigation

revealed that alumni who had been varsity athletes experi-

enced less than half the risk of subsequent stroke death. 5 In

this study we extend our observations regarding physical

activity and stroke incidence among these alumni later in life.

Subjects and Methods

ParticipantsThe Harvard Alumni Health Study is an ongoing study of thepredictors of chronic diseases among men matriculating as under-graduates at Harvard University between 1916 and 1950. We firstmailed a health questionnaire to surviving alumni in either 1962 or1966. After this initial survey, we periodically resurveyed all

Received April 7, 1998; final revision received July 13, 1998; accepted July 13, 1998.From the Department of Epidemiology, Harvard School of Public Health, Boston, Mass (I-M.L., R.S.P); Division of Preventive Medicine, Department

of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, Mass (I-M.L.); and Division of Epidemiology, Stanford UniversitySchool of Medicine, Stanford, Calif (R.S.P.).

This is report No. LXI in a series on chronic disease in former college students.Correspondence to I-Min Lee, MBBS, ScD, Brigham and Womens Hospital, 900 Commonwealth Ave E, Boston, MA 02215. E-mail

[email protected]

Reprint requests to I-Min Lee, MBBS, ScD, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115. 1998 American Heart Association, Inc.

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surviving alumni in the relevant classes to update information onhealth habits and medical history.

For this study we were interested in information from a mailsurvey in 1977. Potentially eligible subjects were 17 835 alumni whoreturned a questionnaire then. We excluded men reporting physician-diagnosed cardiovascular disease or cancer (n2863) to avoidpotential bias from men who recently may have changed theiractivity level because of these diseases. We further excluded men

with missing data on the variables of interest: physical activity,cigarette smoking, alcohol consumption, and ages of parental death(n673). Of the remaining 14 299 men, we successfully followed11 130 (ie, they returned another questionnaire in 1988 or wereknown to have died by 1990; details below), or 78%. These 11 130men formed the study group.

Assessment of Physical Activity and OtherPredictors of StrokeWe asked alumni on the 1977 questionnaire (baseline) to estimate thenumber of blocks walked daily and the number of flights of stairsclimbed daily and to list all sports or recreation in which they hadactively participated during the past year.26 For each sport orrecreation listed, we asked for details regarding frequency (weeksper year) and duration (time per week when active). This assessment

of physical activity has been shown to be reliable and valid. 2733

We analyzed physical activity in 3 different ways. First, weexamined the relation between total energy expended on physicalactivity at baseline and stroke incidence. We estimated total energyexpenditure thus: walking 1 block daily rated 56 kcal/wk; climbing1 flight of stairs daily required 28 kcal/wk. To each sport orrecreation, we assigned a multiple of resting metabolic rate (METscore).34 Since resting metabolic rate is 1 kcal/kg body wt per hour,we estimated the average weekly energy expenditure for that activityby multiplying its MET score by body weight and hours per year ofparticipation, then dividing by 52.35 We summed kilocalories perweek from walking, stair climbing, and sports or recreation toestimate total energy expenditure. We then defined 5 categories:1000 (31.0% of men), 1000 to 1999 (28.7%), 2000 to 2999(18.2%), 3000 to 3999 (10.2%), and 4000 kcal/wk (11.9%).

Second, to understand the effects of specific components ofphysical activity, we examined separately walking, stair climbing,and sports or recreation. We categorized men into approximatefourths of distance walked (1 block0.13 km): 5 (31.8% of men),5 to 10 (21.3%), 10 to 20 (26.2%), and 20 km/wk (20.7%).Similarly, we grouped men into approximate fourths of flightsclimbed (2 flights1 story): 10 (22.9% of men), 10 to 20(21.2%), 20 to 35 (20.8%), and 35 stories/wk (35.1%). Becauseof interest in whether nonvigorous and vigorous activities haveequivalent benefits,36 we calculated separately energy expenditurefrom nonvigorous (6 METs) and vigorous (6 METs) sports orrecreation.35 (Examples of vigorous activities reported by alumniinclude jogging or running, swimming laps, playing tennis, andshoveling snow.) For nonvigorous energy expenditure, we defined 5categories: none (51.1% of men), 1 to 250 (13.8%), 250 to 600(11.7%), 600 to 1400 (12.0%), and 1400 kcal/wk (11.4%). Forvigorous energy expenditure, we did likewise (41.0%, 16.9%,12.1%, 14.7%, and 15.3%, respectively). These cut points werechosen so that among those who did report some sport or recreation,men would be approximately evenly distributed among the remain-ing 4 categories of energy expenditure. Furthermore, the choice ofidentical cut points would enable direct comparison of stroke ratesbetween, for example, men who expended 250 to 600 kcal/wk innonvigorous activities and those who expended the same amount ofenergy but in vigorous activities.

With the growing recognition that it is difficult to persuade the manysedentary individuals25 to take up vigorous activities, research interestlately has focused on moderate intensity physical activity.37 Therefore,we analyzed physical activity in a third way. We calculated the energyexpended on sports or recreation separately for light activities (4.5METs) and for activities of at least moderate intensity (4.5 METs).

(Examples of moderate activities reported by alumni include dancing,bicycling, snorkeling, and digging or filling in garden.) We used the

same cut points as before in analyses. For light energy expenditure, mendistributed themselves thus: none, 63.9%; 1 to 250, 10.3%; 250 to600, 8.2%; 600 to 1400, 8.7%; and 1400 kcal/wk, 8.9%. Forenergy expended on activities of 4.5 METs, the distribution was36.4%, 15.8%, 12.7%, 16.7%, and 18.4%, respectively.

On the 1977 questionnaire, we also asked about cigarette smoking(categorized in analyses as nonsmoker, smoker of 20, or 20cigarettes per day), alcohol consumption (50, 50 to 199, or 200

g/wk), ages of parental death (neither, 1, or both parents died beforeage 65 years), weight and height (combined as body mass index;22.5, 22.5 to 23.5, 23.5 to 24.5, 24.5 to 26.0, or 26.0kg/m2), physician-diagnosed hypertension (no, yes, or unknown),and diabetes mellitus (no, yes, or unknown).

Ascertainment of Stroke OccurrenceIn 1988 we sent another health survey to surviving alumni. Included onthe 1988 survey was a question on whether a physician had everdiagnosed stroke and if so, the year of first diagnosis. Men who did notprovide this information were considered lost to follow-up and excludedfrom study. Self-reported, physician-diagnosed chronic diseases amongalumni were believed to be valid.3840 We used death certificates toascertain additional strokes (underlying or contributing cause of death)not reported on the 1988 questionnaire. We traced deaths occurring

through 1990 using information from the alumni office to obtain deathcertificates. Mortality follow-up in this cohort is 99% complete.38

Statistical AnalysesWe used proportional hazards regression to analyze time to firststroke occurrence (ascertained from the 1988 questionnaire or deathcertificate) or censoring (1988 questionnaire return or death, which-ever occurred later).41 There was no evidence that proportionalhazards assumptions were violated. For strokes ascertained fromdeath certificates alone, we took the date of diagnosis to be the dateof death. Since this could create a potential bias, we first examinedthe association between physical activity and stroke risk, excludingalumni with strokes determined from death certificates. We countedonly cases of stroke ascertained from the 1988 questionnaire inwhich date of diagnosis was known. The findings from these

analyses were similar to those from analyses in which all strokes (ie,determined from the 1988 questionnaire or death certificate) wereincluded. Therefore, we present our findings only from analyses thatcombined strokes ascertained from both sources.

We first modeled rate ratios (relative risks) of stroke as a functionof total energy expenditure and age. We then proceeded to adjustadditionally for other predictors of stroke in these data: cigarettesmoking, alcohol consumption, and early parental death. Sinceage-adjusted and multivariate analyses yielded similar findings, onlyresults from the latter are presented. We calculated 95% CIs forestimated relative risks and used 2-tailed tests of significance.

In secondary analyses, we examined the association between totalenergy expenditure and stroke risk separately for 2 time periods(chosen so that there would be approximately the same number ofevents in each period): 1977 to 1984 and 1985 to 1990, and for 3 age

groups:

65, 65 to 74, and

75 years at study entry. We alsoseparately analyzed a subgroup of men at lower risk of stroke: menwho did not smoke, consumed 200 g/wk of alcohol, and whoseparents did not die before age 65 years.

When analyzing the components of physical activity, we includedindicator terms for categories of walking, stair climbing, nonvigorous(6 METs) energy expenditure, and vigorous (6 METs) energyexpenditure in multivariate models. To assess the effects of light activityand activity of at least moderate intensity, we conducted parallelanalyses with energy expenditure dichotomized at 4.5 instead of 6.0METs. Finally, we investigated the effects of walking and stair climbingamong only men reporting no sports or recreation in 1977.

ResultsAt study entry, alumni were aged 58 years on average (range,

43 to 88 years) (Table 1). Their prevalence of smoking,16.9%, was much lower than in the general population of that

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era (36.5% among US white men, 1979).1 With regard to

body weight, again, alumni possessed a healthier profile,

being of lower body mass index than the general population

of that time.42 Table 1 also describes the distributions of

alcohol consumption, early parental death, and physician-

diagnosed hypertension and diabetes mellitus among

subjects.

Between 1977 and 1990, 378 strokes occurred in 119 880

person-years. For total energy expenditure of1000, 1000 to

1999, 2000 to 2999, 3000 to 3999, and 4000 kcal/wk, the

relative risks of stroke, adjusted for age, smoking, alcohol

intake, and early parental death, were 1.00 (referent), 0.76

(95% CI, 0.59 to 0.98), 0.54 (0.38 to 0.76), 0.78 (0.53 to

1.15), and 0.82 (0.58 to 1.14), respectively;P0.05 for linear

trend (Figure ). When we added a quadratic term for energy

expenditure to examine how well the data fitted a U-shaped

curve, this was significant at P0.004. In assessing the roles

that body mass index, hypertension, and diabetes mellitus

might play in mediating the inverse association between

physical activity and stroke risk, we conducted an analysis

that additionally adjusted for these 3 variables. Relative risks

were slightly attenuated from before: 1.00, 0.79, 0.56, 0.81,and 0.85, respectively; P0.09 for linear trend.

In secondary analyses, we examined separately 2 time

intervals: 1977 to 1984 (176 strokes) and 1985 to 1990 (202

strokes). Relative risks of stroke for the 5 categories of total

energy expenditure during the earlier period were 1.00

(referent), 0.65, 0.55, 0.76, and 0.86, respectively; for the

later period, they were 1.00, 0.86, 0.53, 0.80, and 0.78,

respectively. We also investigated separately men aged 65

(n8344), 65 to 74 (n2259), and 75 years (n527) atstudy entry; 149, 164, and 65 strokes, respectively, occurred.

Among men aged 65 years, the relative risks for the 5

categories of total energy expenditure were 1.00 (referent),

0.75, 0.54, 1.02, and 0.87, respectively. For men aged 65 to

74 years, corresponding relative risks were 1.00, 0.72, 0.52,

0.44, and 0.68, respectively. Among men aged 75 years,

they were 1.00, 0.89, 0.60, 1.10, and 1.28, respectively. These

findings were adjusted for differences in age, smoking,

alcohol consumption, and early parental death.

Next, we analyzed a subgroup of alumni at lower risk for

stroke (men who did not smoke, consumed 200 g/wk of

alcohol, and whose parents did not die before age 65;

n4164; 111 strokes). After adjustment for age and alcohol

intake, the relative risks of stroke for the 5 categories of total

energy expenditure were 1.00 (referent), 0.74, 0.56, 0.63, and

0.84, respectively.

We proceeded to explore the associations between specific

components of physical activity and stroke incidence (Table

2). With walking, attaining a distance of 20 km/wk was

associated with reduced risk. With stair climbing, activities at

6 METs, or activities at 6 METs, we observed a U-shaped

relation of stroke rates to each physical activity component,

similar to that seen for total energy expenditure. However, the

quadratic terms here were not significant (P0.12,P0.22,

andP0.06, respectively). Noteworthy was the similarity ofage-adjusted incidence rates for each level of energy expen-

Relative risks of stroke among Harvard alumni, 1977 to 1990,

according to energy expenditure estimated in kilocalories perweek from blocks walked, stairs climbed, and sports or recre-ational activities performed in 1977. Relative risks are adjustedfor age, cigarette smoking, alcohol consumption, and earlyparental death. Vertical bars indicate 95% CIs.

TABLE 1. Baseline Characteristics of Harvard Alumni in 1977

Characteristic

Mean age, years (SD) 58.0 (8.95)

Cigarette habit, %

Nonsmoker 83.1

Smoker, 120 cigarettes per day 8.5

Smoker, 20 cigarettes per day 8.4

Alcohol consumption, %

50 g/wk 27.2

50200 g/wk 37.1

200 g/wk 35.7

Early (65 years) parental death, %

Neither parent died early 65.8

1 parent died early 29.8

Both parents died early 4.4

Body mass index (kg/m2), %

22.5 23.0

22.523.5 14.4

23.524.5 19.1

24.526.0 20.4

26.0 23.1

Physician-diagnosed hypertension, % 20.1

Physician-diagnosed diabetes mellitus, % 3.9

Energy expenditure (kcal/wk),* %

1000 31.0

10001999 28.7

20002999 18.2

30003999 10.2

4000 11.9

*Estimated from blocks walked, stairs climbed, and sports or recreational

activities performed.

Lee and Paffenbarger October 1998 2051


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diture at 6 METs and the corresponding level of energy

expenditure at 6 METs (eg, for 250 to 600 kcal/wk, 24.0

and 22.9 per 10 000, respectively).When we analyzed energy expenditure for sports or recre-

ation using a 4.5 instead of a 6.0 MET cut point, we observed

that activities of4.5 METs were unrelated to stroke risk

(Table 3). For activities of4.5 METs, a U-shaped relation

was seen with a significant quadratic term (P0.04).

Finally, we investigated another subgroup: men reporting

no sports or recreation in 1977 (n2892; 148 strokes). The

event rate was higher in this than the larger group (data not

shown). The results in this subgroup were similar to those

based on the larger group; however, the findings in this

smaller group were no longer significant. The relative risks of

stroke associated with walking 5, 5 to 10, 10 to 20, and20 km/wk in this subgroup were 1.00 (referent), 1.15, 0.77,

and 0.73, respectively;P0.09 for linear trend. For climbing

10, 10 to 20, 20 to 35, and 35 stories/wk, they were

1.00 (referent), 1.00, 0.60, and 0.94, respectively;P

0.50 forlinear trend.

DiscussionIn these prospective data, physical activity was associated

with decreased risk of stroke in men. With higher levels of

energy expenditure up to 3000 kcal/wk, risk declined

steadily; beyond this, however, the association weakened. We

observed similar findings even in older individuals. What

kinds of activities were beneficial? The data indicated that

walking 20 km/wk was associated with significantly lower

risk, independent of other physical activity components.

Climbing stairs and activities of at least moderate intensity

(4.5 METs) each showed U-shaped relations to stroke risk,with the risk being significantly lower at the nadir of the

curve. Light-intensity activities (4.5 METs), however, were

unrelated to stroke risk. Furthermore, men who participated

in recreational activities experienced lower stroke rates than

those who only walked or climbed stairs but did not engage

in recreational activities.

It is unclear why stroke incidence rates exhibited a

U-shaped relation to physical activity in this study group.

Two of 3 randomized trials specifically testing exercise of

different intensities suggest that higher-intensity physical

activity is less effective in decreasing blood pressure than

lower intensity activity.43,44

This could plausibly explain ourobservations. We did, however, explore whether the

TABLE 2. Incidence Rates* and Relative Risks of Stroke

Among Harvard Alumni, 19771990, According to Different

Components of Physical Activity in 1977

Physical Activity

Component

No. of

Events

Incidence

Rate

(per

10 000)

Multivariate Relative

Risk (95% CI)

Distance walked, km/wk

5 128 34.5 1.00 (referent)

510 81 34.1 1.06 (0.801.40)

1020 105 32.9 1.01 (0.771.31)

20 64 23.6 0.71 (0.520.96)

P0.05 for linear trend

Stairs climbed, stories/wk

10 116 34.8 1.00 (referent)

1020 78 33.3 0.95 (0.711.27)

2035 59 25.0 0.71 (0.520.98)

35 125 31.6 0.97 (0.741.25)


Activities at 6 METs, kcal/wk

None 221 34.3 1.00 (referent)

1250 41 30.7 0.90 (0.641.26)

250600 30 24.0 0.69 (0.471.01)

6001400 40 29.1 0.86 (0.611.21)

1400 46 29.2 0.86 (0.631.19)


Activities at 6 METs, kcal/wk


1250 55 30.6 0.90 (0.671.22)

250600 27 22.9 0.67 (0.451.02)

6001400 35 27.0 0.82 (0.561.18)

1400 44 33.9 1.03 (0.731.44)


METs indicates multiples of resting metabolic rate.

*Age-adjusted.

Adjusted for age (single years), cigarette smoking (nonsmoker, smoker of

20, or 20 cigarettes per day), alcohol consumption (50, 50199, or

200 g/wk), early parental death (neither, 1, or both parents died before age

65), and the other 3 components of physical activity.

TABLE 3. Incidence Rates* and Relative Risks of Stroke

Among Harvard Alumni, 19771990, According to Activities of

4.5 METs in 1977

Physical Activity

Component

No. of

Events

Incidence

Rate

(per

10 000)

Multivariate Relative

Risk (95% CI)

Activities at 4.5 METs, kcal/wk


1250 33 30.2 0.92 (0.641.34)

250600 28 28.2 0.83 (0.561.23)

6001400 30 27.7 0.87 (0.591.27)

1400 39 29.1 0.89 (0.631.25)


Activities at 4.5 METs, kcal/wk


1250 56 32.0 0.88 (0.651.19)

250600 27 21.6 0.60 (0.400.90)

6001400 40 25.7 0.72 (0.511.03)

1400 49 31.3 0.89 (0.641.23)


METs indicates multiples of resting metabolic rate.

*Age-adjusted.

Adjusted for age (single years), cigarette smoking (nonsmoker, smoker of

20, or 20 cigarettes per day), alcohol consumption (50, 50199, or

200 g/wk), early parental death (neither, 1, or both parents died before age

65), walking, and stair climbing, as well as activities of the other intensity.



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U-shaped association might be artifactual. For example, as

alumni aged, perhaps those most active scaled down their

activities, while the less active maintained theirs. We ob-

served some evidence for this: of alumni falling in the least

active category in 1977, 69% remained in the 2 least active

categories in 1988, while 57% of alumni in the most active

category in 1977 remained in the 2 most active categories in1988. This might attenuate relative risks among the most

active, the phenomenon becoming more pronounced as

alumni aged. However, we observed U-shaped associations

during early and late follow-up and among younger and older

men. Thus, physical activity misclassification may not totally

account for the U-shaped association.

Next, we wondered whether men at higher risk for stroke

exercised more assiduously to ameliorate their risk. Although

we did adjust for potential confounders, residual confounding

might still exist. We therefore examined separately men at

lower risk (nonsmokers who drank200 g/wk of alcohol and

whose parents did not die early). Findings were little

changed; thus, residual confounding is less likely to havecaused the U-shaped relation.

Finally, we examined the association between physical

activity and coronary heart disease. The consensus is that

coronary heart disease risk declines steadily with increasing

activity25; thus, if the observed U-shaped curve for stroke

resulted from bias in the design or analysis of the present

study, a U-shaped curve also might be observed for coronary

heart disease in this study group. Among alumni, 1433

developed coronary heart disease (ascertained in similar

fashion as for strokes) during follow-up. After adjustment for

the same potential confounders, the relative risks of this

disease associated with the 5 categories of total energy

expenditure were 1.00 (referent), 0.84, 0.74, 0.83, and 0.71,respectively, with a highly significant linear trend

(P0.0001). Therefore, the U-shaped association between

stroke rates and physical activity is less likely to be an artifact

of the data. Confirmation of this finding requires similar

observations in other populations.

Several investigators have examined dose-response in the

relation between physical activity and stroke.6,810,1317,20,23

Two studies also observed U-shaped relations between stroke

rates and physical activity. In these 2 studies, investigators

categorized physical activity into 3 levels among Italian

railroad workers20 and Seventh-Day Adventist men.23 In 2

other studies in which physical activity was divided into 3

levels, stroke risk decreased at the second level but did not

decline with further activity.14,15 Of the remaining 7 studies

that assessed dose response, stroke risk declined steadily with

increasing activity.6,810,13,16,17 These differences may have

reflected the nature of the different populations studied;

furthermore, physical activity assessments in the various

studies are not directly comparable.

Strengths of the present study include a well-characterized

study group, with detailed and valid physical activity assess-

ment at baseline. The latter enabled investigation of specific

kinds of physical activity, providing useful information for

formulating public health recommendations.

However, several limitations exist. We successfully fol-lowed only 78% of eligible men. Mortality follow-up in this

study group is known to be virtually complete38; hence, those

lost to follow-up were most likely alive as of 1990. Because

they did not return a questionnaire in 1988 (or did so but did

not answer the stroke question), we could not ascertain their

stroke status. Men lost to follow-up (n3169) were younger

at baseline (mean age, 47.2 versus 58.0 years among those in

the present study), somewhat more likely to be smoking

(18.1% versus 16.9%), but less likely to be drinking 200

g/wk of alcohol (32.0% versus 35.7%) and to have both

parents dying early (3.3.% versus 4.4%). The age differential

is not unexpected, since virtually all those lost to follow-up

were alive as of 1990, while those in the present study

included deceased (therefore, older) men as of 1990. How-

ever, the energy expenditure of those lost to follow-up was

quite similar to that of men in the present study (mean, 2212

versus 2104 kcal/wk). This was supported by similar distri-

butions of body mass index in the 2 groups. Since physical

activity levels were similar in the 2 groups of men, bias from

incomplete follow-up is less likely.

Additionally, strokes were ascertained through self-reportand death certificates. Some misclassification was likely,

even though alumni self-report of physician-diagnosed

chronic diseases has been shown to be valid.3840 The mis-

classification is likely to be random, since physical activity

information was collected before asking about stroke. Hence,

the misclassification would likely have weakened findings

but not created spurious inverse associations. We also were

unable to examine different types of stroke since we did not

pursue medical records to determine stroke subtype. Further-

more, we lacked dietary data at baseline and thus could not

adjust for this. However, in about two thirds of men, we did

collect dietary information in 1988. We did not see clear

differences in percent fat or saturated fat intake among menwith different physical activity levels, decreasing the likeli-

hood that diet was a strong confounder. Finally, men in this

study were healthier than the US general population. While

this may limit the generalizability of findings, it does not

preclude their internal validity.

Biologically, it is plausible for physical activity to decrease

stroke risk by curtailing obesity, decreasing blood pressure,

maintaining normal glucose tolerance, and improving insulin

sensitivity.45,46 However, when we additionally adjusted in

analyses for body mass index, hypertension, and diabetes

mellitus, these variables explained only a very modest portion

of the benefit of physical activity. Other pathways through

which physical activity may decrease stroke risk includeimproving lipid profile, decreasing fibrinogen levels, increas-

ing fibrinolytic activity, and reducing the tendency of plate-

lets to aggregate.3

In conclusion, physical activity is associated with de-

creased stroke risk in men, including older men. A decreased

risk was observed at energy expenditures of 1000 to 1999

kcal/wk, with further risk decrement seen at 2000 to 2999

kcal/wk but not beyond. Confirmation of the U-shaped

relation observed in these data requires similar observations

in other populations.

Acknowledgments

This study was supported by grants from the National Heart, Lung,and Blood Institute (HL 34174) and the National Cancer Institute

Lee and Paffenbarger October 1998 2053


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(CA 44854), US Public Health Service. We are grateful to StaceyDeCaro, Sarah E. Freeman, Tina Y. Ha, James B. Kampert, Rita W.Leung, Doris C. Rosoff, Howard D. Sesso, and Alvin L. Wing fortheir help with the College Alumni Health Study.

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