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Christie M. Ballantyne, MD; Ron C. Hoogeveen, PhD; Heejung Bang, PhD; Josef Coresh, MD, PhD; Aaron R. Folsom, MD, MPH; Lloyd E. Chambless, PhD; Merle Myerson, MD, EdD; Kenneth K. Wu, MD, PhD; A. Richey Sharrett, MD, DrPH; Eric Boerwinkle, PhD

Arch Intern Med. 2005;165:2479-2484.

Background  Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a proinflammatory enzyme secreted by macrophages. We assessed Lp-PLA₂ and C-reactive protein (CRP) levels along with traditional risk factors to examine their relation to ischemic stroke.

Methods  A proportional hazards model was used in a prospective case-cohort study of 12 762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study who were observed for about 6 years.

Results  Mean Lp-PLA₂ and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 noncases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different. Both Lp-PLA₂ and CRP levels were associated with ischemic stroke after adjustment for age, sex, and race: hazard ratios were 2.23 for the highest vs the lowest tertile of Lp-PLA₂ and 2.70 for CRP level higher than 3 vs lower than 1 mg/L. In a model that included smoking, systolic hypertension, lipid levels, and diabetes, Lp-PLA₂ and CRP levels in the highest category were associated with hazard ratios of 1.91 (95% confidence interval, 1.15-3.18; P = .01) and 1.87 (95% confidence interval, 1.13-3.10; P = .02), respectively. Individuals with high levels of both CRP and Lp-PLA₂ were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk.

Conclusion  Levels of Lp-PLA₂ and CRP may be complementary beyond traditional risk factors in identifying middle-aged individuals at increased risk for ischemic stroke.

Author Affiliations: Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Tex (Drs Ballantyne and Hoogeveen); Department of Biostatistics, School of Public Health, The University of North Carolina at Chapel Hill (Drs Bang and Chambless); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md (Drs Coresh and Sharrett); Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (Dr Folsom); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (Dr Myerson); and Vascular Biology Research Center, Department of Internal Medicine (Dr Wu), and the Human Genetics Center, School of Public Health (Dr Boerwinkle), The University of Texas Health Science Center at Houston.

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