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

• Published in: Stroke (1970) 2009-02, Vol.40 (2), p.376-381
• Main Authors: Nambi, Vijay, Hoogeveen, Ron C, Chambless, Lloyd, Hu, Yijuan, Bang, Heejung, Coresh, Josef, Ni, Hanyu, Boerwinkle, Eric, Mosley, Thomas, Sharrett, Richey, Folsom, Aaron R, Ballantyne, Christie M
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase - analysis; Adult; Aged; Atherosclerosis - epidemiology; Biological and medical sciences; Biomarkers; Brain Ischemia - complications; Brain Ischemia - epidemiology; C-Reactive Protein - analysis; Cohort Studies; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Inflammation - epidemiology; Linear Models; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Stroke - classification; Stroke - epidemiology; Stroke - etiology; United States; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.107.513259

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 (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.