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.
OBJECTIVE
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.
Nambi
Vijay
V
Department of Medicine, Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. cmb@bcm.tmc.edu
Hoogeveen
Ron C
RC
Chambless
Lloyd
L
Hu
Yijuan
Y
Bang
Heejung
H
Coresh
Josef
J
Ni
Hanyu
H
Boerwinkle
Eric
E
Mosley
Thomas
T
Sharrett
Richey
R
Folsom
Aaron R
AR
Ballantyne
Christie M
CM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000032:analysis*; D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology*; D015415:Biomarkers; D002545:Brain Ischemia / Q000150:complications / Q000453:epidemiology; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000145:classification / Q000453:epidemiology* / Q000209:etiology; D014481:United States
D015415:Biomarkers; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase