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)

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

doi:10.1186/s12881-014-0140-3

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)

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	140
Journal	BMC Medical Genetics
Volume	15
DOIs	https://doi.org/10.1186/s12881-014-0140-3
Publication status	Published - 21 Dec 2014
Externally published	Yes

Keywords

Aged
Aged, 80 and over
Clinical Trials as Topic
Coronary Artery Disease/complications
Genetic Predisposition to Disease
Heart Failure, Systolic/genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prognosis

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Haver, V. G., Verweij, N., Kjekshus, J., Fox, J. C., Wedel, H., Wikstrand, J., van Gilst, W. H., de Boer, R. A., van Veldhuisen, D. J., & van der Harst, P. (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). BMC Medical Genetics, 15, 140. https://doi.org/10.1186/s12881-014-0140-3

@article{ab8b64fc860a444686c452bd87f6601f,

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))).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.",

keywords = "Aged, Aged, 80 and over, Clinical Trials as Topic, Coronary Artery Disease/complications, Genetic Predisposition to Disease, Heart Failure, Systolic/genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Prognosis",

author = "Haver, {Vincent G} and Niek Verweij and John Kjekshus and Fox, {Jayne C} and Hans Wedel and John Wikstrand and {van Gilst}, {Wiek H} and {de Boer}, {Rudolf A} and {van Veldhuisen}, {Dirk J} and {van der Harst}, Pim",

year = "2014",

month = dec,

day = "21",

doi = "10.1186/s12881-014-0140-3",

language = "English",

volume = "15",

pages = "140",

journal = "BMC Medical Genetics",

issn = "1471-2350",

publisher = "BioMed Central",

}

Haver, VG, Verweij, N, Kjekshus, J, Fox, JC, Wedel, H, Wikstrand, J, van Gilst, WH, de Boer, RA, van Veldhuisen, DJ & van der Harst, P 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)', BMC Medical Genetics, vol. 15, pp. 140. https://doi.org/10.1186/s12881-014-0140-3

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, Vincent G; Verweij, Niek; Kjekshus, John et al.
In: BMC Medical Genetics, Vol. 15, 21.12.2014, p. 140.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The impact of coronary artery disease risk loci on ischemic heart failure severity and prognosis

T2 - association analysis in the COntrolled ROsuvastatin multiNAtional trial in heart failure (CORONA)

AU - Haver, Vincent G

AU - Verweij, Niek

AU - Kjekshus, John

AU - Fox, Jayne C

AU - Wedel, Hans

AU - Wikstrand, John

AU - van Gilst, Wiek H

AU - de Boer, Rudolf A

AU - van Veldhuisen, Dirk J

AU - van der Harst, Pim

PY - 2014/12/21

Y1 - 2014/12/21

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Clinical Trials as Topic

KW - Coronary Artery Disease/complications

KW - Genetic Predisposition to Disease

KW - Heart Failure, Systolic/genetics

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Prognosis

U2 - 10.1186/s12881-014-0140-3

DO - 10.1186/s12881-014-0140-3

M3 - Article

C2 - 25528061

SN - 1471-2350

VL - 15

SP - 140

JO - BMC Medical Genetics

JF - BMC Medical Genetics

ER -

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

Keywords

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