title: Lipoprotein associated phospholipase A2 activity, apolipoprotein C3 loss-of-function variants and cardiovascular disease: The Atherosclerosis Risk In Communities Study.
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.
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: yashashwi.pokharel@bcm.edu.
authors.forename: Yashashwi
authors.initials: Y
authors.lastname: Pokharel
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address: wsun@bcm.edu.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Sun
authors.affiliation: University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: Linda.M.Whitaker@uth.tmc.edu.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Polfus
authors.affiliation: School of Public Health, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: folso001@umn.edu.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: gerardo_heiss@unc.edu.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.affiliation: Bloomberg School of Public Health, Department of Epidemiology, Johns Hopkins University, Baltimore, MD, USA. Electronic address: rsharret@jhu.edu.
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.affiliation: University of Texas Health Science Center at Houston, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. Electronic address: Eric.Boerwinkle@uth.tmc.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.edu.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: ronh@bcm.edu.
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000483:Alleles; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019518:Postprandial Period; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000235:genetics / Q000378:metabolism; D014481:United States
chemical_list: D053305:Apolipoprotein C-III; D008071:Lipoprotein Lipase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase
keywords: Apolipoprotein C3 loss-of-function; Atherogenic dyslipidemia; Atherosclerosis Risk In Communities Study; Cardiovascular disease; Coronary heart disease; Ischemic stroke; Lipoprotein-associated phospholipase A(2) activity