Published Online
on June 1, 2006

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

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Submitted on January 7, 2006
Revised on February 24, 2006
Accepted on March 21, 2006

C-Reactive Protein as a Predictor of Incident Ischemic Stroke Among Patients With Preexisting Cardiovascular Disease

David Tanne MD^*; Michal Benderly PhD; Uri Goldbourt PhD; Moti Haim MD; Alexander Tenenbaum MD, PhD; Enrique Z. Fisman MD; Zipora Matas PhD; Yehuda Adler MD; Reuven Zimmlichman MD; and Solomon Behar MD

From the Stroke Center, Department of Neurology (D.T.), Neufeld Cardiac Research Institute (M.B., U.G., S.B.), and Cardiac Rehabilitation Institute (A.T., Y.A., E.Z.F.), Sheba Medical Center, Tel Hashomer; Cardiology Department, Rabin Medical Center, Petach Tikva (M.H.); Chemistry Laboratory, Wolsfon Medical Center, Holon (Z.M., R.Z.); and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (D.T., M.B., U.G., M.H., Z.M., R.Z., A.T., Y.A., E.Z.F., S.B.), Israel.

^* To whom correspondence should be addressed. E-mail: tanne{at}post.tau.ac.il.

Background and Purpose--C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk.

Methods--We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years.

Results--Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels.

Conclusions--These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Key words: epidemiology • inflammation • risk factors • stroke

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