Lipoprotein associated phospholipase A2 activity, apolipoprotein C3 loss-of-function variants and cardiovascular disease: The Atherosclerosis Risk In Communities Study

Objective: Lipoprotein-associated phospholipase A(2) (LpPLA(2)) activity was associated with higher CHD risk in a meta-analysis, which was partly dependent on circulating lipid levels. Apolipoprotein C3 loss-of-function (ApoC3 LOF) mutations were related with reduced postprandial lipemia and CHD risk. However, the association of LpPLA(2) activity with ApoC3 LOF is not known. Methods: We examined the association of LpPLA(2) activity and ApoC3 LOF mutations and incident cardiovascular disease (CVD) (defined as coronary heart disease [CHD] plus ischemic stroke) and all-cause mortality in the biracial longitudinal Atherosclerosis Risk In Communities (ARIC) study. Results: The mean LpPLA(2) activity was 229.3 nmol/min/mL and was higher in men and whites. LpPLA(2) activity correlated positively with atherogenic dyslipidemia. ApoC3 LOF carriers had lower LpPLA(2) activity levels compared to non-carriers, and there was inverse association between LpPLA(2) activity and ApoC3 LOF mutations in whites. In a fully adjusted model, greater LpPLA(2) activity was independently associated with incident CVD (HR 1.35, 1.09-1.68 for highest vs. lowest quintile), which was mainly explained by its association with CHD, and was also associated with all-cause mortality (HR 1.65, 1.38-1.98). Conclusions: Greater LpPLA(2) activity was associated with increased CHD and all-cause mortality in both whites and AfricaneAmericans in the ARIC study. The inverse relation between LpPLA2 activity and ApoC3 LOF mutations suggests that delayed lipoprotein clearance may at least in part explain the observed association of LpPLA(2) activity with increased CVD risk. (C) 2015 Elsevier Ireland Ltd. All rights reserved.