Lipoprotein-Associated Phospholipase A 2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population

Abstract

Background— Chronic inflammation represents an essential feature of the atherosclerotic process. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an enzyme mainly produced by monocytes/macrophages, generates potent proinflammatory products. Methods and Results— Plasma concentrations of Lp-PLA 2 were determined by ELISA in 934 apparently healthy men aged 45 to 64 years sampled from the general population in 1984 and followed up until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA (MONItoring of trends and determinants in CArdiovascular disease) protocol. Baseline levels of Lp-PLA 2 were higher in subjects who experienced an event than in event-free subjects (295±113 versus 263±79 ng/mL, P <0.01). Lp-PLA 2 was positively correlated with total cholesterol ( R =0.30, P <0.0001) and age ( R =0.12, P =0.001), was only slightly correlated with HDL cholesterol ( R =0.09, P =0.005) and C-reactive protein R =0.06, P =0.06), but was not correlated with body mass index or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA 2 was associated with risk of future coronary events (hazard ratio [HR] 1.37, 95% CI 1.16 to 1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23, 95% CI 1.02 to 1.47). Further inclusion of C-reactive protein in the model did not appreciably affect its predictive ability (HR 1.21, 95% CI 1.01 to 1.45). Conclusions— Elevated levels of Lp-PLA 2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA 2 and CRP may be additive in their ability to predict risk of coronary heart disease.