Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study.
BACKGROUND
Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme secreted by macrophages. We assessed Lp-PLA2 and C-reactive protein (CRP) levels along with traditional risk factors to examine their relation to ischemic stroke.


METHODS
A proportional hazards model was used in a prospective case-cohort study of 12,762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study who were observed for about 6 years.


RESULTS
Mean Lp-PLA2 and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 noncases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different. Both Lp-PLA2 and CRP levels were associated with ischemic stroke after adjustment for age, sex, and race: hazard ratios were 2.23 for the highest vs the lowest tertile of Lp-PLA2 and 2.70 for CRP level higher than 3 vs lower than 1 mg/L. In a model that included smoking, systolic hypertension, lipid levels, and diabetes, Lp-PLA2 and CRP levels in the highest category were associated with hazard ratios of 1.91 (95% confidence interval, 1.15-3.18; P = .01) and 1.87 (95% confidence interval, 1.13-3.10; P = .02), respectively. Individuals with high levels of both CRP and Lp-PLA2 were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk.


CONCLUSIONS
Levels of Lp-PLA2 and CRP may be complementary beyond traditional risk factors in identifying middle-aged individuals at increased risk for ischemic stroke.
Ballantyne
Christie M
CM
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, Tex 77030, USA. cmb@bcm.tmc.edu
Hoogeveen
Ron C
RC
Bang
Heejung
H
Coresh
Josef
J
Folsom
Aaron R
AR
Chambless
Lloyd E
LE
Myerson
Merle
M
Wu
Kenneth K
KK
Sharrett
A Richey
AR
Boerwinkle
Eric
E
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D050197:Atherosclerosis / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D002097:C-Reactive Protein / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D012189:Retrospective Studies; D012307:Risk Factors
D015415:Biomarkers; D008078:Cholesterol, LDL; D002097:C-Reactive Protein; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase