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. Methods and 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 ≈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-PLA ₂ 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.