Objective: Lipoprotein-associated phospholipase A2 (LpPLA2) 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 LpPLA2 activity with ApoC3 LOF is not known. Methods: We examined the association of LpPLA2 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 LpPLA2 activity was 229.3nmol/min/mL and was higher in men and whites. LpPLA2 activity correlated positively with atherogenic dyslipidemia. ApoC3 LOF carriers had lower LpPLA2 activity levels compared to non-carriers, and there was inverse association between LpPLA2 activity and ApoC3 LOF mutations in whites. In a fully adjusted model, greater LpPLA2 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 LpPLA2 activity was associated with increased CHD and all-cause mortality in both whites and African-Americans 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 LpPLA2 activity with increased CVD risk.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Aug 1 2015|
Bibliographical noteFunding Information:
Dr. Pokharel is supported by American Heart Association SWA Summer 2014 Postdoctoral Fellowship Award (15POST23080014) and 2015-2016 seed grant from the American Medical Association Foundation. Dr. Hoogeveen received a research grant from DiaDexus, which provided reagents to conduct the LpPLA 2 activity assays but they had no role in study design, data analysis, or manuscript preparation. All other authors report no conflicts.
Ancillary study support has been provided by National Heart, Lung, and Blood Institute sponsored project (RC2HL102419). Sequencing was carried out at the Baylor Genome Center (U54 HG003273).
© 2015 Elsevier Ireland Ltd.
- ApoC3 LOF
- Apolipoprotein C3 loss-of-function
- Atherogenic dyslipidemia
- Atherosclerosis Risk In Communities Study
- Cardiovascular disease
- Coronary heart disease
- Ischemic stroke
- Lipoprotein-associated phospholipase A activity
- SOLID-TIMI 52