Published Online
on October 2, 2006

A more recent version of this article appeared on October 10, 2006

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Submitted on February 9, 2006
Revised on July 7, 2006
Accepted on July 14, 2006

High Serum C-Reactive Protein Level Is Not an Independent Predictor for Stroke. The Rotterdam Study

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

From the Departments of Epidemiology and Biostatistics (M.J.B., M.A.S., J.C.M.W., A.H., 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--Current guidelines recommend the assessment of C-reactive protein (CRP) levels with a high-sensitivity assay in cardiovascular risk prediction. Recent studies have put forward that although elevated CRP is a risk factor for cardiovascular disease, it is not helpful in the prediction of cardiovascular disease risk. We studied the importance of CRP as a risk factor and as a risk predictor of future stroke.

Methods and Results--The present study was based on 6430 participants of the Rotterdam Study who at baseline (1990-1993) were 55 years of age, were stroke free, and had blood taken. Strokes were classified as hemorrhagic, ischemic, or unspecified. Ischemic strokes were further subclassified. Whether stroke risk varied with baseline CRP serum levels was assessed with Cox proportional hazards models. Whether CRP was helpful in the prediction of individual stroke risk was assessed with receiver operating characteristic curves and by comparing the distribution of strokes between predicted risk strata. During an average of 8.2 years of follow-up, 498 first-ever strokes occurred. High CRP levels were significantly associated with risk of any stroke (age- and sex-adjusted hazard ratio per SD, 1.14; 95% confidence interval, 1.04 to 1.24) and risk of ischemic stroke (age- and sex-adjusted hazard ratio per SD, 1.17; 95% confidence interval, 1.04 to 1.32). Taking CRP levels into account did not improve the individual stroke risk prediction, however, regardless of whether it was based on the Framingham stroke risk score or on age and sex only.

Conclusions--Although CRP levels are associated with stroke risk, their use in the assessment of individual stroke risk seems limited.

Key words: C-reactive protein • cerebral infarction • inflammation • risk factors • stroke

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