Lipoprotein associated Phospholipase A 2 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, 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 African-Americans in the ARIC study. The inverse relation between LpPLA 2 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.

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