Published Online
on December 18, 2008

A more recent version of this article appeared on February 1, 2009

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Submitted on December 21, 2007
Revised on June 7, 2008
Accepted on June 24, 2008

Lipoprotein-Associated Phospholipase A₂ and High-Sensitivity C-Reactive Protein Improve the Stratification of Ischemic Stroke Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Vijay Nambi MD; Ron C. Hoogeveen PhD; Lloyd Chambless PhD; Yijuan Hu; Heejung Bang PhD; Josef Coresh MD, PhD; Hanyu Ni PhD; Eric Boerwinkle PhD; Thomas Mosley PhD; Richey Sharrett MD; Aaron R. Folsom MD; and Christie M. Ballantyne MD^*

From the Section of Atherosclerosis and Vascular Medicine, Department of Medicine (V.N., R.C.H., C.M.B.), Baylor College of Medicine, Houston, Texas; the Center for Cardiovascular Disease Prevention (V.N., R.C.H., C.M.B.), Methodist DeBakey Heart Center, Houston, Texas; the Department of Biostatistics (L.C., Y.H.), University of North Carolina, Chapel Hill, NC; the Division of Biostatistics and Epidemiology, Department of Public Health (H.B.), Weill Medical College of Cornell University, New York, NY; the Department of Epidemiology (J.C., R.S.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Md; the National Institute of Health (H.N.), Bethesda, Md; the Human Genetics Center and Institute of Molecular Medicine (E.B.), University of Texas–Houston Health Science Center, Houston, Texas; the Department of Medicine (T.M.), University of Mississippi, Jackson, Miss; and the Division of Epidemiology and Community Health (A.R.F.), University of Minnesota School of Public Health, Minneapolis, Minn.

^* To whom correspondence should be addressed. E-mail: cmb{at}bcm.tmc.edu.

Background and Purpose—Inflammation plays a critical role in the development of vascular disease, and increased levels of the inflammatory biomarkers, lipoprotein-associated phospholipase A₂ (Lp-PLA₂), and high-sensitivity C-reactive protein (hs-CRP) have been shown to be associated with an increased risk for ischemic stroke.

Methods—In a prospective case–cohort (n=949) study in 12 762 apparently healthy, middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study, we first examined whether Lp-PLA₂ and hs-CRP levels improved the area under the receiver operator characteristic curve (AUC) for 5-year ischemic stroke risk. We then examined how Lp-PLA₂ and hs-CRP levels altered classification of individuals into low-, intermediate-, or high-risk categories compared with traditional risk factors.

Results—In a model using traditional risk factors alone, the AUC adjusted for optimism was 0.732, whereas adding hs-CRP improved the AUC to 0.743, and adding Lp-PLA₂ significantly improved the AUC to 0.752. Addition of hs-CRP and Lp-PLA₂ together in the model improved the AUC to 0.761, and the addition of the interaction between Lp-PLA₂ and hs-CRP further significantly improved the AUC to 0.774. With the use of traditional risk factors to assess 5-year risk for ischemic stroke, 86% of participants were categorized as low risk (<2%); 11%, intermediate risk (2% to 5%); and 3%, high risk (>5%). The addition of hs-CRP, Lp-PLA₂, and their interaction to the model reclassified 4%, 39%, and 34% of the low-, intermediate- and high-risk categories, respectively.

Conclusion—Lp-PLA₂ and hs-CRP may be useful in individuals classified as intermediate risk for ischemic stroke by traditional risk factors.

Key words: CRP • Lp-PLA₂ • risk • stroke

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