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Open Access 01-12-2014 | Research article

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)

Authors: Vincent G Haver, Niek Verweij, John Kjekshus, Jayne C Fox, Hans Wedel, John Wikstrand, Wiek H van Gilst, Rudolf A de Boer, Dirk J van Veldhuisen, Pim van der Harst

Published in: BMC Medical Genetics | Issue 1/2014

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)).

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.

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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)
Authors: Vincent G Haver
Niek Verweij
John Kjekshus
Jayne C Fox
Hans Wedel
John Wikstrand
Wiek H van Gilst
Rudolf A de Boer
Dirk J van Veldhuisen
Pim van der Harst
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-014-0140-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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