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Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

ABSTRACT: Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weighted genetic risk score (wGRS) was calculated as the sum of risk alleles multiplied by the hazard ratio for a particular SNP. In single variant analyses, rs579459, rs4420638, and rs2107595 were associated with an increased risk of MACE. A wGRS was further constructed to evaluate the cumulative effect of the 3 SNPs on the prognosis of CAD. The risk of MACE among patients with high and intermediate wGRS was 1.968- and 1.838-fold, respectively, higher than those with low wGRS. This effect was more evident in patients using lipid-lowering medication and with hypertension. Furthermore, the interaction analysis revealed that lipid-lowering medication and hypertension interacted with the genetic effect off wGRS on the risk of MACE in patients using lipid-lowering medication or with hypertension (Pinteraction?

SUBMITTER: Zhao C

PROVIDER: S-EPMC5758289 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

Zhao Chen C Zhu Pin P Shen Qile Q Jin Li L

Medicine 20171201 51

Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weigh ...[more]

PMID: 29390587

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Project description:Background & aimsHepatic steatosis has been associated with increased risk of major adverse cardiovascular events (MACE) but it is not clear whether steatosis is independently associated with risk of MACE. We investigated whether steatosis is associated with risk of MACE independently of the presence and extent of baseline coronary artery disease, assessed by comprehensive contrast-enhanced computed tomography angiography (CTA).MethodsWe conducted a nested cohort study of 3756 subjects (mean age, 60.6 years; 48.4% men) who underwent coronary CTA at 193 sites in North America, from July 2010 through September 2013, as part of the PROMISE study, which included noninvasive cardiovascular analyses of symptomatic outpatients without coronary artery disease. Independent core laboratory readers measured hepatic and splenic attenuation, using non-contrast computed tomography images to identify steatosis, and evaluated coronary plaques and stenosis in coronary CTA images. We collected data on participants' cardiovascular risk factors, presence of metabolic syndrome, and body mass index. The primary endpoint was an adjudicated composite of MACE (death, myocardial infarction, or unstable angina) during a median follow-up time of 25 months.ResultsAmong the 959 subjects who had steatosis (25.5% of the cohort), 42 had MACE (4.4%), whereas among the 2797 subjects without steatosis, 73 had MACE (2.6%) (hazard ratio [HR] for MACE in subjects with steatosis, 1.69; 95% CI, 1.16-2.48; P = .006 for MACE in subjects with vs without steatosis). This association remained after adjustment for atherosclerotic cardiovascular disease risk scores, significant stenosis, and metabolic syndrome (adjusted HR, 1.72; 95% CI, 1.16-2.54; P = .007) or obesity (adjusted HR, 1.75; 95% CI, 1.19-2.59; P = .005). Steatosis remained independently associated with MACE after adjustment for all CTA measures of plaques and stenosis.ConclusionsHepatic steatosis is associated with MACE independently of other cardiovascular risk factors or extent of coronary artery disease. Strategies to reduce steatosis might reduce risk of MACE. ClinicalTrials.gov no: NCT01174550.

Project description:ImportanceAcute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown.ObjectiveTo determine the association between mental stress-induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes among individuals with stable coronary artery disease.Design, setting, and participantsThis cohort study was conducted at a university-affiliated hospital network between June 2011 and August 2014. A cohort of individuals with stable coronary artery disease were included. Data analysis took place from November 2018 to May 2019.ExposuresStudy participants were subjected to a laboratory mental stress task (public speaking).Main outcomes and measuresFlow-mediated vasodilation was measured before and 30 minutes after a public-speaking mental stress task. We examined the association of the rest (prestress), poststress, and δ flow-mediated vasodilation (poststress minus prestress levels) with an adjudicated composite end point of adverse events, including cardiovascular death, myocardial infarction, unstable angina leading to revascularization, and heart failure hospitalization, after adjusting for sociodemographic factors, medical history, and depression.ResultsA total of 569 patients were included (mean [SD] age, 62.6 [9.3] years; 420 men [73.8%]). Flow-mediated vasodilation decreased from a mean (SD) of 4.8% (3.7%) before mental stress to 3.9% (3.6%) after mental stress (a 23% reduction; P < .001), and 360 participants (63.3%) developed transient endothelial dysfunction (a decrease in flow-mediated vasodilation). During a median (interquartile range) follow-up period of 3.0 (2.9-3.1) years, 74 patients experienced a major adverse cardiovascular event. The presence of transient endothelial dysfunction with mental stress was associated with a 78% increase (subdistribution hazard ratio [sHR], 1.78 [95% CI, 1.15-2.76]) in the incidence of major adverse cardiovascular event. Both the δ flow-mediated vasodilation (sHR, 1.15 [95% CI, 1.03-1.27] for each 1% decline) and poststress flow-mediated vasodilation (sHR, 1.14 [95% CI, 1.04-1.24] for each 1% decline) were associated with major adverse cardiovascular event. Risk discrimination statistics demonstrated a significant model improvement after addition of either poststress flow-mediated vasodilation (change in the area under the curve, 0.05 [95% CI, 0.01-0.09]) or prestress plus δ flow-mediated vasodilation (change in the area under the curve, 0.04 [95% CI, 0.00-0.08]) compared with conventional risk factors.Conclusions and relevanceIn this study, transient endothelial dysfunction with mental stress was associated with adverse cardiovascular outcomes in patients with coronary artery disease. Endothelial responses to stress represent a possible mechanism through which psychological stress may affect outcomes in patients with coronary artery disease.

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Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

Publications

Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

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