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)

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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)

Haver, V. G. (author)

Verweij, N. (author)

Kjekshus, J. (author)

Fox, J. C. (author)

Wedel, H. (author)

Wikstrand, John, 1938 (author): Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory

Van Gilst, W. H. (author)

de Boer, R. A. (author)

van Veldhuisen, D. J. (author)

van der Harst, P. (author)

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(creator_code:org_t)

2014-12-21
2014
English.
In: Bmc Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15:140

Related links:: https://bmcmedgenet....; show more...; https://gup.ub.gu.se...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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 x 10(-7)) and apolipoprotein B (P = 2.2 x 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

Coronary artery disease
Heart failure
Genetics
Healthy ageing
SNP
SUSCEPTIBILITY LOCI
CARDIOMYOPATHY
CHOLESTEROL
DESIGN
9P21
Genetics & Heredity

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art (subject category)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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