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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).

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.

SUBMITTER: Haver VG

PROVIDER: S-EPMC4412120 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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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 Vincent G VG Verweij Niek N Kjekshus John J Fox Jayne C JC Wedel Hans H Wikstrand John J van Gilst Wiek H WH de Boer Rudolf A RA van Veldhuisen Dirk J DJ van der Harst Pim P

BMC medical genetics 20141221

<h4>Background</h4>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.<h4>Methods</h4>We undertook association analysis of 7 single nucleotide polymorphism (rs599839, rs17465637, rs2972147, rs6922269, rs1333049, rs501120, and rs17228212) at 7 well established CAD risk loci ...[more]

PMID: 25528061

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Project description:BackgroundWe have previously demonstrated an association between increased sFRP3 expression and adverse outcome in a population of HF irrespective of cause and left ventricular ejection fraction. In this study we evaluated the prognostic value of sFRP3 in older patients with chronic systolic HF of ischemic origin.MethodsWe evaluated sFRP3, by tertiles, as a risk factor for the primary endpoint (cardiovascular [CV] mortality, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV mortality, death from worsening HF (WHF), any coronary event, including sudden death, as well as hospitalizations for CV causes and WHF in 1444 patients from the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo.ResultsKaplan-Meier curves for the primary endpoint, as well as all-cause- and CV mortality revealed a markedly better survival for patients with sFRP3 levels in the middle tertile of compared to the 1st and 3rd tertile. In multivariable Cox-regression, after full adjustment including high-sensitive CRP and NT-proBNP, a lower event rate for the primary end point, all cause and CV mortality was observed for patients with tertile 2 sFRP3 levels (HR 0.57 [0.44-0.74], 0.55 [0.44-0.74] and 0.52 [0.39-0.69]; p<0.001), as well as for the number of coronary events (HR 0.62 [0.47-0.82], p = 0.001) and sudden death (HR 0.55 [0.37-0.82], p = 0.002). Applying sFRP3 values to the fully adjusted regression model resulted in highly significant continuous net reclassification improvements for the primary endpoint, all cause and CV mortality, coronary events and sudden death (range 0.24-0.31; p≤0.002 for all).ConclusionsIntermediate serum sFRP3 levels are associated with better survival and fewer CV events than low or high sFRP3 levels, independently of conventional risk factors, in older patients with chronic systolic HF of ischemic origin. Our study suggests that balanced Wnt activity might confer protective effects in a clinical HF setting.Trial registrationhttp://www.clinicaltrials.gov NCT00206310.

Project description:AimsCoronary artery disease (CAD) is a common cause of heart failure (HF). It remains unclear who, when and why to direct towards coronary revascularization. The outcomes of coronary revascularization in HF patients are still a matter of debate nowadays. This study aims to evaluate the effect of revascularization strategy on all-cause of death in the context of ischaemic HF.Methods and resultsAn observational cohort was conducted on 692 consecutive patients who underwent coronary angiography at the University Hospital of Toulouse between January 2018 and December 2021 for either a recent diagnosis of HF or a decompensated chronic HF, and in whom coronary angiograms showed at least 50% obstructive coronary lesion. The study population was divided into two groups according to the performance or not of a coronary revascularization procedure. The living status (alive or dead) of each of the study's participants was observed by April 2022. Seventy-three per cent of the study population underwent coronary revascularization either by percutaneous coronary intervention (66.6%) or coronary artery bypass grafting (6.2%). Baseline characteristics including age, sex and cardiovascular risk factors did not differ between the invasive and conservative groups, respectively. Death occurred in 162 study participants resulting in an all-cause mortality rate of 23.5%; 26.7% of observed deaths have occurred in the conservative group versus 22.2% in the invasive group (P = 0.208). No difference in survival outcomes has been observed over a mean follow-up period of 2.5 years (P = 0.140) even after stratification by HF categories (P = 0.132) or revascularization modalities (P = 0.366).ConclusionsFindings from the present study showed comparable all-cause mortality rates between groups. Coronary revascularization does not modify short-term survival outcomes in HF patients compared with optimal medical therapy alone outside the setting of acute coronary syndrome.

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Project description:ObjectiveChronic kidney disease is a known risk factor in cardiovascular disease, but its influence on treatment effect of bypass surgery remains unclear. We assessed the influence of chronic kidney disease on 10-year mortality and cardiovascular outcomes in patients with ischemic heart failure treated with medical therapy (medical treatment) with or without coronary artery bypass grafting.MethodsWe calculated the baseline estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula, chronic kidney disease stages 1-5) from 1209 patients randomized to medical treatment or coronary artery bypass grafting in the Surgical Treatment for IsChemic Heart failure trial and assessed its effect on outcome.ResultsIn the overall Surgical Treatment for IsChemic Heart failure cohort, patients with chronic kidney disease stages 3 to 5 were older than those with stages 1 and 2 (66-71 years vs 54-59 years) and had more comorbidities. Multivariable modeling revealed an inverse association between estimated glomerular filtration rate and risk of death, cardiovascular death, or cardiovascular rehospitalization (all P < .001, but not for stroke, P = .697). Baseline characteristics of the 2 treatment arms were equal for each chronic kidney disease stage. There were significant improvements in death or cardiovascular rehospitalization with coronary artery bypass grafting (stage 1: hazard ratio, 0.71; confidence interval, 0.53-0.96, P = .02; stage 2: hazard ratio, 0.71; confidence interval, 0.59-0.84, P < .0001; stage 3: hazard ratio, 0.76; confidence interval, 0.53-0.96, P = .03). These data were inconclusive in stages 4 and 5 for insufficient patient numbers (N = 28). There was no significant interaction of estimated glomerular filtration rate with the treatment effect of coronary artery bypass grafting (P = .25 for death and P = .54 for death or cardiovascular rehospitalization).ConclusionsChronic kidney disease is an independent risk factor for mortality in patients with ischemic heart failure with or without coronary artery bypass grafting. However, mild to moderate chronic kidney disease does not appear to influence long-term treatment effects of coronary artery bypass grafting.

Dataset Information

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).

Publications

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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