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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.

TitleLipoprotein-associated phospholipase A2 and high-sensitivity C-reactive protein improve the stratification of ischemic stroke risk in the Atherosclerosis Risk in Communities (ARIC) study.
Publication TypeJournal Article
Year of Publication2009
AuthorsNambi V, Hoogeveen RC, Chambless L, Hu Y, Bang H, Coresh J, Ni H, Boerwinkle E, Mosley T, Sharrett R, Folsom AR, Ballantyne CM
JournalStroke
Volume40
Issue2
Pagination376-81
Date Published2009 Feb
ISSN1524-4628
Keywords1-Alkyl-2-acetylglycerophosphocholine Esterase, Adult, Aged, Atherosclerosis, Biomarkers, Brain Ischemia, C-Reactive Protein, Cohort Studies, Female, Humans, Inflammation, Linear Models, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Stroke, United States
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 (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.

DOI10.1161/STROKEAHA.107.513259
Alternate JournalStroke
PubMed ID19095974
PubMed Central IDPMC2711777
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01 HC055022 / HC / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States