Published Online
on May 4, 2006

A more recent version of this article appeared on June 1, 2006

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Submitted on December 12, 2005
Revised on February 9, 2006
Accepted on March 8, 2006

Uric Acid Is a Risk Factor for Myocardial Infarction and Stroke. The Rotterdam Study

Michiel J. Bos MD, MSc; Peter J. Koudstaal MD, PhD; Albert Hofman MD, PhD; Jacqueline C.M. Witteman PhD; and Monique M.B. Breteler MD, PhD^*

From the Departments of Epidemiology & Biostatistics (M.J.B., A.H., J.C.M.W., M.M.B.B.) and Neurology (M.J.B., P.J.K.), Erasmus Medical Center, Rotterdam, The Netherlands.

^* To whom correspondence should be addressed. E-mail: m.breteler{at}erasmusmc.nl.

Background and Purpose--The role of uric acid as a risk factor for myocardial infarction is controversial, and little is known about its role as a risk factor for stroke. Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease, for example, by inducing renal disease and hence hypertension. We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospective population-based study.

Methods--The study was based on 4385 participants of the Rotterdam Study who, at baseline (1990 to 1993), were 55 years of age, free from stroke and coronary heart disease, and had blood taken. Follow-up for incident stroke and myocardial infarction was complete until January 1, 2002. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders.

Results--Average follow-up was 8.4 years. High serum uric acid levels were associated with risk of myocardial infarction and stroke; age- and sex-adjusted hazard ratios (95% CIs) for highest versus lowest quintile of uric acid were 1.68 (1.24 to 2.27) for cardiovascular disease (515 cases), 1.87 (1.12 to 3.13) for myocardial infarction (194 cases), 1.57 (1.11 to 2.22) for stroke (381 cases), 1.77 (1.10 to 2.83) for ischemic stroke (205 cases), and 1.68 (0.68 to 4.15) for hemorrhagic stroke (46 cases). Adjustment for other vascular risk factors only slightly attenuated these associations. Associations were stronger in persons without hypertension than in those with hypertension.

Conclusions--Uric acid is a strong risk factor for myocardial infarction and stroke.

Key words: cerebrovascular disorders • epidemiology • risk factors • stroke • myocardial infarction

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