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 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 approximate to 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.