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Received September 17, 1997; final revision received November 6, 1997; accepted November 21, 1997.
From the Department of Neurology (R.L.S., R.G., B.B.-A., D.E.K., W.A.H., I-F.L.); Sergievsky Center (R.L.S., W.A.H.); Division of Epidemiology
(R.L.S., W.A.H., S.S.); Department of Medicine (Division of General Medicine) (S.S.); and Division of Biostatistics (I-F.L., M.C.P.), Columbia University
College of Physicians and Surgeons and School of Public Health, New York, NY.
Presented in part in abstract form at the 48th Annual Meeting of the American Academy of Neurology, San Francisco, Calif, March 2330, 1996.
Correspondence to Ralph L. Sacco, MD, MS, Neurological Institute, 710 W 168 St, New York, NY 10032. E-mail RLS1@Columbia.edu
1998 American Heart Association, Inc.
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Sacco et al
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Data were collected through interview of the case and control subjects
by trained research assistants, review of the medical records, physical
and neurological examination by the study physicians, in-person
measurements, and fasting blood specimens for lipid and glucose
measurements. Data were obtained directly from study subjects by
means of standardized data collection instruments. When the subject
was unable to answer questions because of death, aphasia, coma,
dementia, or other conditions, a proxy who was knowledgeable about
the patients history was interviewed (data were obtained from the
study subject in 74% of case subjects). Stroke-free control subjects
were interviewed in person and evaluated in the same manner as case
subjects (data were obtained from the study subject in 99% of control
subjects). Case subjects were interviewed as soon as possible after their
stroke, within a median time of 4 days from stroke onset.
All assessments were conducted in English or Spanish depending on
the primary language of the participant. Race/ethnicity was based on
self-identification through a series of interview questions modeled
after the US census. All participants responding affirmatively to being
of Spanish origin or identifying themselves as Hispanic were classified
as such. All participants classifying themselves as white without any
Hispanic origin or black without any Hispanic origin were classified as
white, non-Hispanic, or black, non-Hispanic, respectively.
Subjects were interviewed regarding sociodemographic characteristics, stroke risk factors, and other medical conditions. Standardized
questions were adapted from the Behavioral Risk Factor Surveillance
System by the Centers for Disease Control and Prevention regarding
the following conditions: hypertension, diabetes, hypercholesterolemia, peripheral vascular disease, transient ischemic attack, cigarette
smoking, alcohol use, and cardiac conditions such as myocardial
infarction, coronary artery disease, angina, congestive heart failure,
atrial fibrillation, other arrhythmias, and valvular heart disease.16
Subjects also completed a comprehensive functional status battery,
which included the Barthel ADL, the QWB , and the Geriatric Social
Readjustment Rating scales.1719
Blood pressure was measured with the use of a calibrated standard
aneroid sphygmomanometer (Omron). After the subject had 5 minutes of relative immobility in a sitting position, two blood pressure
measurements separated by 15 minutes were recorded. In subjects
with blood pressure recordings discrepant by .10 mm Hg, a third
measurement was obtained by the study physician and entered into the
database along with the closer blood pressure reading by the research
assistant. Anthropometric measurements of height and weight were
determined by the use of calibrated scales. Blood samples were sent for
complete blood count on admission or enrollment. Fasting glucose
was measured with a Hitachi 747 automated spectrometer (Boehringer). Fasting lipid panels (including total cholesterol, LDL, HDL, and
triglyceride) were measured with a Hitachi 705 automated spectrometer (Boehringer).
Hypertension was defined as a systolic blood pressure recording
$160 mm Hg or a diastolic blood pressure recording $95 mm Hg
(based on the average of the two blood pressure measurements) or the
patients self-report of a history of hypertension or antihypertensive
use. Diabetes mellitus was defined by a fasting glucose .140 mg/dL
(7.7 mmol/L), the patients self-report of such a history, or insulin or
hypoglycemic use. For this analysis, smoking was defined as currently
smoking cigarettes, and heavy alcohol use was defined as current
drinking of $14 drinks per week. BMI was calculated as weight
(kilograms) divided by height (meters) squared, and obesity was
defined as BMI $27.8 for men and $27.3 for women.1
382
horseback riding, and gardening) and heavy (hiking, tennis, swimming, bicycle riding, jogging, aerobic dancing, and handball or
racquetball or squash). A series of yes/no responses were recorded for
each of the questions, posed as In the last 2 weeks, have you engaged
in
for physical activity? For stroke case subjects,
the question was phrased as In the last 2 weeks prior to your
stroke . . . . Each affirmative response was followed by two other
questions: On average, how many times did you perform this activity
over the last 2 weeks? and On average, how many minutes each
time? From these responses the frequency and duration of each
activity were computed.
TABLE 1.
Control Subjects
(n5678)
White
63 (17%)
121 (18%)
Black
106 (29%)
204 (30%)
Hispanic
196 (53%)
349 (51%)
206 (56%)
394 (58%)
Mean6SD
70.0612.4
69.8611.8
Age $65
254 (69%)
472 (70%)
116 (32%)
307 (45%)
295 (80%)
584 (86%)
Hypertension
264 (72%)
393 (58%)
Diabetes
140 (38%)
131 (19%)
Demographics
Race/ethnicity
Sex
Statistical Analyses
Female
Results
From July 1, 1993, to December 31, 1995, 369 case subjects
with first cerebral infarction and 678 age-, sex-, and race/
ethnicity-matched control subjects were enrolled in the casecontrol study. Among the case subjects, 7% died within 30 days
of the stroke, and both fatal and nonfatal strokes were included
in the analyses. Overall, there were 18% whites, 30% blacks,
and 52% Hispanics. Mean age was 69.9612 years, and women
constituted 57%. Hypertension, diabetes, peripheral vascular
disease, smoking, and cardiac disease were more common
among the case subjects, while obesity was more prevalent
among the control subjects. The control subjects were slightly
more educated and were enrolled slightly more frequently
during nonwinter months than the case subjects (Table 1).
Only 16% of the case and control subjects were working .10
h/wk at the time of enrollment. Based on the recruitment
telephone-interview data, our nonresponse analysis showed
that control subjects who participated in person had a similar
frequency of hypertension, diabetes, and cardiac disease but
were more likely to be overweight and smoke cigarettes than
subjects who did not participate.
Age, y
Education
$HS graduate
Season of enrollment
Nonwinter*
Risk factors
PVD
85 (23%)
89 (13%)
Smoking
81 (23%)
117 (18%)
Cardiac disease\
141 (39%)
158 (23%)
Obesity
128 (37%)
286 (42%)
33 (9%)
43 (7%)
Sacco et al
TABLE 2.
383
Control Subjects
Hours/Week
Hours/Week
Never
179 (49%)
174 (25%)
Any activities
190 (51%)
4.064.4
504 (75%)
4.764.8
Light
186 (50%)
3.864.4
489 (72%)
4.564.6
174 (47%)
3.663.5
468 (69%)
4.264.4
20 (5%)
1.561.5
106 (16%)
1.561.4
1.761.7
Walking
Calisthenics
Dancing
3 (1%)
5.368.4
13 (2.0%)
Golf
2 (1%)
18.5623.3
4 (1%)
1069.7
Gardening
1 (0.3%)
6 (1%)
2.463.7
Bowling
0 (0%)
2 (0.3%)
1.860.4
Horseback riding
3.360
0
0 (0%)
0 (0%)
16 (4%)
2.261.8
64 (9%)
2.463.4
Bicycle
6 (2%)
2.261.5
17 (3%)
2.563.7
Swimming
0 (0%)
13 (2%)
1.661.3
Hiking
0 (0%)
3 (0.4%)
1.861.0
Tennis
0 (0%)
2 (0.3%)
0.7561.7
Aerobic dance
8 (2%)
2.361.1
Jogging
4 (1%)
0.860.6
Handball
0 (0%)
Moderate/heavy
Moderate
Heavy
28 (4%)
9 (1.3%)
0 (0%)
2.163.9
2.262.75
0
384
Discussion
The cardiovascular benefits of physical activity have been
emphasized by numerous organizations, including the Centers
for Disease Control, National Institutes of Health, and the
American Heart Association. Recent guidelines recommended
that individuals perform moderate exercise for approximately
3.5 h/wk. This suggestion arose from accumulating data
regarding the beneficial effects of physical activity in reducing
the incidence of heart disease. The benefits for stroke, however, have not always been consistent across age and sex
subgroups. Furthermore, little is known about physical activity
Sacco et al
The dose-response relationship between increasing amounts
of physical activity and the reduction in the risk of stroke has
not always been demonstrated. Wannamethee and Shaper11
found an inverse relationship between physical activity and risk
of stroke, but the benefit of vigorous physical activity for stroke
was offset by an increased risk of heart attack. In Framingham
among the older cohort, the strongest protective effect was
detected in the medium tertile physical activity subgroup, with
no additional benefit gained from higher levels of physical
activity.6 Among subjects in a case-control study in West
Birmingham, UK, who were free of cardiac disease, peripheral
vascular disease, and poor health, recent vigorous exercise was
no more protective than walking.12
The protective effect of physical activity may be partly
mediated through its role in controlling various known risk
factors for stroke. Exercise has been shown to lower blood
pressure in certain groups.26 28 It is also associated with a lower
incidence of cardiovascular disease,29 32 improved diabetes
control,33,34 better dietary habits, and lower body weight.35,36
Cigarette smokers are less likely to participate in exercise
programs.37 Furthermore, people with a higher level of education participate in more leisure-time activity.38 The finding
of an independent effect of physical activity after adjustment
for these factors suggests that mechanisms other than the
control of risk factors may be responsible for the protective
effect of physical activity for stroke.
Other biological mechanisms are also associated with physical activity, including reductions in plasma fibrinogen and
platelet activity and elevations in plasma tissue plasminogen
activator activity and HDL concentrations.39 42 In a preliminary analysis from our multiethnic population, we found HDL
concentration to be inversely related to the risk of stroke.43
However, we found no significant differences in plasma HDL
levels among our inactive, light-moderately active, and heavily
active groups in either our case or control subjects, and the
independent effect of physical activity remained after HDL and
other lipid levels were added to our model in a subgroup
analysis.
There are some limitations to our study. Our design was a
case-control study and not a prospective cohort study. However, our subjects were population based, and selection bias is
less likely than in hospital-based case-control studies. The OR
more closely approximates a relative risk in population-based
case-control studies, since the case and control subjects are
derived from the same community and provide a close
approximation of the prevalence of exposure in those with and
without incident disease.44 Recall bias, a frequent source of bias
in case-control studies, seems less likely since the case and
control subjects were not aware of the hypotheses being tested.
In addition, recall physical activity surveys like the instrument
we used are less likely to influence a subjects typical behavior
than activity diaries or logs.22
There may have been some unmeasured confounders that
led to a reduction in recent physical activity among the stroke
case subjects or influenced the selection of control subjects
who were more physically active. This could have resulted in
an overestimation of the OR. However, we made a concerted
effort to adjust for such confounders in our analyses and
performed nonresponse analyses which showed that the con-
385
386
21.
Acknowledgments
This study was supported by grants from the National Institute of
Neurological Disorders and Stroke (R01 NS 27517, R01 NS 29993,
and T32 NS 07153) and the General Clinical Research Center (2 M01
RR00645). We acknowledge the support of Dr J.P. Mohr, Director
of Cerebrovascular Research; the statistical assistance of Qiong Gu;
the processing of the lipids by Drs Henry Ginsberg and Lars F.
Berglund in the Division of Preventive Medicine and Nutrition and
the Irving Center for Clinical Research; and the help provided by Drs
J. Kirk Roberts and Mitchell S. Elkind, fellows in stroke
and neuroepidemiology.
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Stroke. 1998;29:380-387
doi: 10.1161/01.STR.29.2.380
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