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Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.

ABSTRACT: Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.Peripheral blood samples from 338 subjects aged 62?±?11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N?=?175, and replication N?=?163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.In both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio?=?8.5, P?

SUBMITTER: Kim J

PROVIDER: S-EPMC4071233 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.

Kim Jinhee J Ghasemzadeh Nima N Eapen Danny J DJ Chung Neo Christopher NC Storey John D JD Quyyumi Arshed A AA Gibson Greg G

Genome medicine 20140530 5

<h4>Background</h4>Genetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.<h4>Methods</h4>Peripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followe ...[more]

PMID: 24971157

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Project description:ImportancePatients who survive acute myocardial infarction (AMI) have a high risk of subsequent major cardiovascular events. Efforts to identify risk factors for recurrence have primarily focused on the period immediately following AMI admission.ObjectivesTo identify risk factors and develop and evaluate a risk model that predicts 1-year cardiovascular events after AMI.Design, setting, and participantsProspective cohort study. Patients with AMI (n?=?4227), aged 18 years or older, discharged alive from 53 acute-care hospitals across China from January 1, 2013, to July 17, 2014. Patients were randomly divided into samples: training (50% [2113 patients]), test (25% [1057 patients]), and validation (25% [1057 patients]). Risk factors were identified by a Cox model with Markov chain Monte Carlo simulation and further evaluated by latent class analysis. Analyses were conducted from May 1, 2017, to January 21, 2018.Main outcomes and measuresMajor cardiovascular events, including recurrent AMI, stroke, heart failure, and death, within 1 year after discharge for the index AMI hospitalization.ResultsThe mean (SD) age of the cohort was 60.8 (11.8) years and 994 of 4227 patients (23.5%) were female. Common comorbidities included hypertension (2358 patients [55.8%]), coronary heart disease (1798 patients [42.5%]), and dyslipidemia (1290 patients [30.5%]). One-year event rates were 8.1% (95% CI, 6.91%-9.24%), 9.0% (95% CI, 7.22%-10.70%), and 6.4% (95% CI, 4.89%-7.85%) for the training, test, and validation samples, respectively. Nineteen risk factors comprising 15 unique variables (age, education, prior AMI, prior ventricular tachycardia or fibrillation, hypertension, angina, prearrival medical assistance, >4 hours from onset of symptoms to admission, ejection fraction, renal dysfunction, heart rate, systolic blood pressure, white blood cell count, blood glucose, and in-hospital complications) were identified. In the training, test, and validation samples, respectively, the risk model had C statistics of 0.79 (95% CI, 0.75-0.83), 0.73 (95% CI, 0.68-0.78), and 0.77 (95% CI, 0.70-0.83) and a predictive range of 1.2% to 33.9%, 1.2% to 37.9%, and 1.3% to 34.3%. The C statistic was 0.69 (95% CI, 0.65-0.74) for the latent class model in the training data. The risk model stratified 11.3%, 81.0%, and 7.7% of patients to high-, average-, and low-risk groups, with respective probabilities of 0.32, 0.06, and 0.01 for 1-year events.Conclusions and relevanceNineteen risk factors were identified, and a model was developed and evaluated to predict risk of 1-year cardiovascular events after AMI. This may aid clinicians in identifying high-risk patients who would benefit most from intensive follow-up and aggressive risk factor reduction.

Project description:Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI.A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status.In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04).A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.

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Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.

Publications

Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.

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