Lipoprotein-Associated Phospholipase A 2 , 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 A 2 (Lp-PLA 2 ) 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-PLA 2 , 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-PLA 2 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-PLA 2 and 2.53 for the highest category of CRP versus the lowest categories. Lp-PLA 2 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-PLA 2 with CHD was attenuated and not statistically significant. For individuals with LDL-C below the median (130 mg/dL), Lp-PLA 2 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-PLA 2 and CRP levels in the highest tertile were at the greatest risk for a CHD event. Conclusions— Lp-PLA 2 and CRP may be complementary in identifying individuals at high CHD risk who have low LDL-C.