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

TitleLipoprotein associated phospholipase A2 activity, apolipoprotein C3 loss-of-function variants and cardiovascular disease: The Atherosclerosis Risk In Communities Study.
Publication TypeJournal Article
Year of Publication2015
AuthorsPokharel, Y, Sun, W, Polfus, LM, Folsom, AR, Heiss, G, A Sharrett, R, Boerwinkle, E, Ballantyne, CM, Hoogeveen, RC
JournalAtherosclerosis
Volume241
Issue2
Pagination641-8
Date Published2015 Aug
ISSN1879-1484
Keywords1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Alleles, Apolipoprotein C-III, Atherosclerosis, Cardiovascular Diseases, Dyslipidemias, Female, Humans, Lipoprotein Lipase, Male, Middle Aged, Mutation, Postprandial Period, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, United States
Abstract

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 229.3 nmol/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.

DOI10.1016/j.atherosclerosis.2015.06.033
Alternate JournalAtherosclerosis
PubMed ID26117401
PubMed Central IDPMC4731876
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
U54HG003273 / HG / NHGRI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100008 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100005 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
RC2HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100011 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100009 / HL / NHLBI NIH HHS / United States