From the Department of Biostatistics, University of Washington, Seattle
(R.A.K.); Division of Neurology, Department of Medicine (R.G.H.), and
Department of Clinical Pharmacology (R.L.T.), University of Texas, San
Antonio; Division of Epidemiology and Clinical Applications, National Heart,
Lung, and Blood Institute, Bethesda, Md (T.A.M.); Neuroradiology Division,
Johns Hopkins University, Baltimore, Md (N.J.B.); and Department of Geriatric
Medicine, University of Pittsburgh (Pa) (A.N.).
Correspondence to Richard A. Kronmal, PhD, Cardiovascular Health Study, 1501 Fourth Ave, Suite 2105, Seattle, WA 98101. E-mail kronmal{at}biostat.washington.edu
Background and Purpose—Randomized
clinical trials testing aspirin in relatively low-risk, middle-aged
people have consistently shown small increases in stroke
associated with aspirin use. We analyzed the relationship
between the regular use of aspirin and incident ischemic and
hemorrhagic stroke among people aged 65 years or older participating in
the Cardiovascular Health Study.
Methods—We conducted a multivariate
analysis of incident stroke rates in a prospectively assessed,
observational cohort of 5011 elderly people followed for a mean of 4.2
years.
Results—Participants had a mean age of 72 years, and 58% were
women. Twenty-three percent used aspirin frequently, and 17% used
aspirin infrequently at study entry. Frequent aspirin use was
associated with an increased rate of ischemic stroke compared
with nonusers (relative risk=1.6; 95% confidence interval
[CI], 1.2 to 2.2; P=0.001). After adjustment for other
stroke risk factors, women who used aspirin frequently or infrequently
at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95%
CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively
(P<0.01, test for trend), compared with
nonusers. In men, aspirin use was not statistically
significantly associated with stroke risk. Findings were similar when
aspirin use in the years before the incident stroke was used in the
modeling. Aspirin use at entry was also associated with a 4-fold (95%
CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both
infrequent and frequent users of aspirin (P=0.003).
Conclusions—Aspirin use was associated with increased risks of
ischemic stroke in women and hemorrhagic stroke overall in this
elderly cohort, after adjustment for other stroke predictors. The
possibility exists of confounding by reasons for aspirin use rather
than cause and effect. Whether regular aspirin use increases stroke
risk for elderly people without cardiovascular disease
can only be determined by randomized clinical trials.
© 1998 American Heart Association, Inc.
Original Contributions
Aspirin Use and Incident Stroke in the Cardiovascular Health Study
Key Words: aspirin • cerebral infarction • cerebral hemorrhage • elderly • risk factors • stroke
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