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Publication . Article . Other literature type . 2014

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)

association analysis in the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA)
Vincent G. Haver; Niek Verweij; John Kjekshus; Jayne C. Fox; Hans Wedel; John Wikstrand; Wiek H. van Gilst; +3 Authors
Open Access

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)). Conclusion 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.

Subjects by Vocabulary

Microsoft Academic Graph classification: Cardiomyopathy medicine.disease medicine Myocardial infarction Framingham Risk Score Etiology Cardiology medicine.medical_specialty Heart failure Coronary artery disease Internal medicine business.industry business Cholesterol chemistry.chemical_compound chemistry Rosuvastatin medicine.drug


Research Article, Coronary artery disease, Heart failure, Genetics, Healthy ageing, SNP, Aged, Aged, 80 and over, Clinical Trials as Topic, Genetic Predisposition to Disease, Heart Failure, Systolic, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Genetics (clinical), SUSCEPTIBILITY LOCI, CARDIOMYOPATHY, CHOLESTEROL, DESIGN, 9P21, Genetics(clinical)

Funded by
  • Funder: Wellcome Trust (WT)