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

Abstract

Background and purpose: Inflammation plays a critical role in the development of vascular disease, and increased levels of the inflammatory biomarkers, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), 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-PLA(2) 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-PLA(2) 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-PLA(2) significantly improved the AUC to 0.752. Addition of hs-CRP and Lp-PLA(2) together in the model improved the AUC to 0.761, and the addition of the interaction between Lp-PLA(2) 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-PLA(2), and their interaction to the model reclassified 4%, 39%, and 34% of the low-, intermediate- and high-risk categories, respectively.

Conclusions: Lp-PLA(2) and hs-CRP may be useful in individuals classified as intermediate risk for ischemic stroke by traditional risk factors.