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(Circulation. 2003;107:2016.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

C-Reactive Protein and the Future Risk of Thromboembolic Stroke in Healthy Men

J. David Curb, MD; Robert D. Abbott, PhD; Beatriz L. Rodriguez, MD, PhD; Pamela Sakkinen, MD, MPH; Jordan S. Popper, MD; Katsuhiko Yano, MD; Russell P. Tracy, PhD

From the Pacific Health Research Institute (J.D.C., R.D.A., B.L.R., K.Y.), Honolulu, Hawaii; the Division of Biostatistics and Epidemiology, University of Virginia School of Medicine (R.D.A.), Charlottesville, Va; Honolulu Heart Program, Kuakini Medical Center (J.D.C., R.D.A., B.L.R., K.Y.), Honolulu, Hawaii; the Departments of Geriatric Medicine and Medicine, John A. Burns School of Medicine, University of Hawaii (J.D.C., B.L.R.), Honolulu, Hawaii; and the Laboratory for Clinical Biochemistry Research, University of Vermont (P.S., R.P.T.), Colchester, Vt.

Correspondence to J. David Curb, MD, Pacific Health Research Institute, 846 S. Hotel St, Suite 301, Honolulu, HI 96813. E-mail curb{at}phri.hawaii-health.com

Background— Evidence suggests that C-reactive protein (CRP) is related to thromboembolic (TE) stroke. Whether associations are altered in the presence of other risk factors is unclear. The purpose of this study was to additionally assess the relation between CRP and TE stroke.

Methods and Results— On the basis of 20 years of follow-up after CRP measurement, 259 cases of TE stroke were identified and compared with 1348 controls. Subjects were aged 48 to 70 years when CRP was measured. Levels of CRP were positively associated with TE stroke throughout the 20 years of follow-up. Although associations were modest within 5 years of CRP measurement, the odds of stroke in the top versus bottom CRP quartile increased over time to a 3.8-fold excess by 10 to 15 years into follow-up (P<0.001). For men without hypertension or diabetes, the overall corresponding odds were 1.6 to 1.7 (P<0.05). In men 55 years of age, the odds increased to a 3-fold excess (P=0.006), and in nonsmokers, there was a 5.8-fold excess (P<0.001). Associations in past and current smokers, in men >55 years of age, and in those with hypertension or diabetes were not significant.

Conclusions— Findings suggest that elevated CRP in middle adulthood and in men with healthier risk factor profiles may be important as a risk factor for TE stroke. Use of CRP levels as a clinical screen to identify an increased risk of cardiovascular disease in otherwise healthy men warrants consideration.

Key Words: stroke • inflammation • epidemiology

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