title: 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: 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.
authors.affiliation: Department of Medicine, Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. cmb@bcm.tmc.edu
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Lloyd
authors.initials: L
authors.lastname: Chambless
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Hu
authors.forename: Heejung
authors.initials: H
authors.lastname: Bang
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Hanyu
authors.initials: H
authors.lastname: Ni
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Thomas
authors.initials: T
authors.lastname: Mosley
authors.forename: Richey
authors.initials: R
authors.lastname: Sharrett
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: 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
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase