title: The impact of coronary artery disease risk loci on ischemic heart failure severity and prognosis: association analysis in the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA).
abstract: BACKGROUND
  Recent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD). The impact of these loci on the disease severity and prognosis of ischemic heart failure due to CAD is currently unknown.
  
  
  METHODS
  We undertook association analysis of 7 single nucleotide polymorphism (rs599839, rs17465637, rs2972147, rs6922269, rs1333049, rs501120, and rs17228212) at 7 well established CAD risk loci (1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21, and 15q22.33, respectively) in 3,320 subjects diagnosed with systolic heart failure of ischemic aetiology and participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) trial. The primary outcome was the composite of time to first event of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, secondary outcomes included mortality and hospitalization due to worsening heart failure.
  
  
  RESULTS
  None of the 7 loci were significantly associated with the primary composite endpoint of the CORONA trial (death from cardiovascular cases, nonfatal myocardial infarction, and nonfatal stroke). However, the 1p13.3 locus (rs599839) showed evidence for association with all-cause mortality (after adjustment for covariates; HR 0.74, 95%CI [0.61 to 0.90]; P = 0.0025) and we confirmed the 1p13.3 locus (rs599839) to be associated with lipid parameters (total cholesterol (P = 1.1x10(-4)), low-density lipoprotein levels (P = 3.5 × 10(-7)) and apolipoprotein B (P = 2.2 × 10(-10))).
  
  
  CONCLUSIONS
  Genetic variants strongly associated with CAD risk are not associated with the severity and outcome of ischemic heart failure. The observed association of the 1p13.3 locus with all-cause mortality requires confirmation in further studies.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. v.g.haver@umcg.nl.
authors.forename: Vincent G
authors.initials: VG
authors.lastname: Haver
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. n.verweij@umcg.nl.
authors.forename: Niek
authors.initials: N
authors.lastname: Verweij
authors.affiliation: Department of Cardiology, University of Oslo and Oslo University Hospital, Oslo, Norway. john.kjekshus@medisin.uio.no.
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.affiliation: AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK. jayne.fox@astrazeneca.com.
authors.forename: Jayne C
authors.initials: JC
authors.lastname: Fox
authors.affiliation: Nordic School of Public Health, Göteborg, Sweden. hans.wedel@biostat.se.
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
authors.affiliation: Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. john.wikstrand@wlab.gu.se.
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. w.h.van.gilst@umcg.nl.
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. r.a.de.boer@umcg.nl.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. d.j.van.veldhuisen@umcg.nl.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. p.van.der.harst@umcg.nl.|University of Groningen, University Medical Center Groningen, Department of Genetics, Hanzeplein 1, 9713GZ, Groningen, The Netherlands. p.van.der.harst@umcg.nl.|Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511GC, Utrecht, The Netherlands. p.van.der.harst@umcg.nl.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics* / Q000401:mortality; D020022:Genetic Predisposition to Disease; D054143:Heart Failure, Systolic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis