Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study.
BACKGROUND
Measuring C-reactive protein (CRP) has been recommended to identify patients at high risk for coronary heart disease (CHD) with low LDL cholesterol (LDL-C). Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a proinflammatory enzyme associated primarily with LDL.


RESULTS
In a prospective, case cohort study in 12 819 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities study, the relation between Lp-PLA2, CRP, traditional risk factors, and risk for CHD events over a period of approximately 6 years was examined in a proportional hazards model, stratified by LDL-C. Lp-PLA2 and CRP levels were higher in the 608 cases than the 740 noncases. Both Lp-PLA2 and CRP were associated with incident CHD after adjustment for age, sex, and race with a hazard ratio of 1.78 for the highest tertile of Lp-PLA2 and 2.53 for the highest category of CRP versus the lowest categories. Lp-PLA2 correlated positively with LDL-C (r=0.36) and negatively with HDL-C (r=-0.33) but not with CRP (r=-0.05). In a model adjusted for traditional risk factors including LDL-C, the association of Lp-PLA2 with CHD was attenuated and not statistically significant. For individuals with LDL-C below the median (130 mg/dL), Lp-PLA2 and CRP were both significantly and independently associated with CHD in fully adjusted models. For individuals with LDL-C <130 mg/dL, those with both Lp-PLA2 and CRP levels in the highest tertile were at the greatest risk for a CHD event.


CONCLUSIONS
Lp-PLA2 and CRP may be complementary in identifying individuals at high CHD risk who have low LDL-C.
Ballantyne
Christie M
CM
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, and 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
Heiss
Gerardo
G
Sharrett
A Richey
AR
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001161:Arteriosclerosis / Q000201:enzymology / Q000453:epidemiology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis*; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000201:enzymology / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D002097:C-Reactive Protein; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase