Dataset Information

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

ABSTRACT:

Objectives

Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology.

Setting

107 secondary and tertiary cardiac surgery centres across the USA.

Participants

We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included.

Primary and secondary outcome measures

The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution.

Results

Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation.

Conclusions

Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.

SUBMITTER: Kertai MD

PROVIDER: S-EPMC4431169 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Publications

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

Kertai Miklos D MD Li Yi-Ju YJ Li Yen-Wei YW Ji Yunqi Y Alexander John J Newman Mark F MF Smith Peter K PK Joseph Diane D Mathew Joseph P JP Podgoreanu Mihai V MV

BMJ open 20150506 5

<h4>Objectives</h4>Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology.<h4>Setting</h4>107 secondary and tertiary c ...[more]

PMID: 25948407

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Project description:BackgroundWomen have been underrepresented in the literature; the effects of female sex on outcomes in patients with acute myocardial infarction (AMI) remain unclear.ObjectivesThis study compares the real-world outcomes of women and men with AMI who have undergone revascularization via percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).MethodsThis is a retrospective cohort study utilizing data from the Taiwan National Health Insurance database. We identified patients who were admitted for AMI and who underwent coronary revascularization during the index admission period between January 1, 2001, and December 31, 2013. Patients were then categorized based on the treatment received into PCI and CABG groups. In-hospital and long-term outcomes were compared between women and men in each group. Interaction tests were then performed to determine whether the differences between sexes were modified by the mode of revascularization. Analyses were repeated after propensity score matching between women and men in each group to minimize possible confounders. We also conducted subgroup analyses, stratifying by the presence of diabetes mellitus, congestive heart failure, and chronic kidney disease.ResultsWe enrolled 67,534 patients who met the inclusion criteria in the analysis; 60,207 patients had undergone PCI (13,514 female and 46,693 male), while 7327 patients had received CABG (1762 female and 5565 male). Prior to matching, enrolled female patients were older on average, with more comorbidities. In-hospital and long-term outcomes were worse in women, particularly in the PCI group. After matching, the incidence of hospitalization for heart failure (HHF) was higher in women (10.4% vs 8.0%, OR 1.32, 95% CI 1.22-1.43), with fewer repeat revascularizations (28.1% vs 32.4%, OR 0.84, 95% CI 0.81-0.88). Both observations were more pronounced in the PCI group (HHF: P for interaction = 0.0496; repeat revascularization: P for interaction = 0.021).ConclusionsWomen presenting with AMI exhibited worse in-hospital and long-term outcomes than men, especially among women who received PCI as the initial mode of revascularization. Women who underwent PCI were more likely to be admitted for heart failure during follow-up. Possible socioeconomic inequalities or a distinct pathobiology of cardiac ischemia between sexes may underlie these results; thus, further investigation is needed.

Project description:BackgroundMyocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction.MethodsWe assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and cardiac magnetic resonance imaging (CMR) using both late gadolinium enhancement (LGE) and ultrasmall superparamagnetic particles of iron oxide (USPIO).ResultsSystemic humoral inflammatory biomarkers (myeloperoxidase, interleukin-6, interleukin-8 and c-reactive protein) increased in the post-operative period with C-reactive protein concentrations plateauing by 48 h (median area under the curve (AUC) 7530 [interquartile range (IQR) 6088 to 9027] mg/L/48 h). USPIO-defined cellular myocardial inflammation ranged from normal to those associated with type 1 myocardial infarction (median 80.2 [IQR 67.4 to 104.8] /s). Plasma hs-cTnI concentrations rose by ≥50-fold from baseline and exceeded 10-fold the upper limit of normal in all patients. Two distinct patterns of peak cTnI release were observed at 6 and 24 h. After CABG surgery, new LGE was seen in 20% (n = 18) of patients although clinical peri-operative type 5 myocardial infarction was diagnosed in only 9% (n = 8). LGE was associated with the delayed 24-h peak in hs-cTnI and its magnitude correlated with AUC plasma hs-cTnI concentrations (r = 0.33, p < 0.01) but not systemic inflammation, myocardial inflammation or bypass time.ConclusionPatients undergoing CABG surgery invariably have plasma hs-cTnI concentrations >10-fold the 99th centile upper limit of normal that is not attributable to inflammatory or ischemic injury alone. Peri-operative type 5 myocardial infarction is often unrecognised and is associated with a delayed 24-h peak in plasma hs-cTnI concentrations.

Project description:ObjectiveApproximately 10% of patients undergoing cardiac surgery have perioperative myocardial injury. A recent genome-wide association study identified an association between myocardial infarction in nonsurgical populations and common genetic variants on chromosome 9p21. We hypothesized that these variants are also associated with perioperative myocardial injury after isolated primary coronary artery bypass graft surgery.MethodsIn a prospective observational study of 846 Caucasian patients undergoing primary coronary bypass surgery at 2 US centers, we genotyped 61 linkage-disequilibrium tagging single nucleotide polymorphisms, encompassing 436 kbp of the 9p21 region. A multivariable logistic model was used to adjust for previously identified clinical covariates of perioperative myocardial injury. Perioperative myocardial injury was defined as a postoperative day 1 cardiac troponin I in the top 10th percentile (>9.13 microg/L) of the cohort. Multiple testing of single nucleotide polymorphisms was corrected for with family-wise errors.ResultsPrior myocardial infarction and longer cardiopulmonary bypass time were significant independent predictors of perioperative myocardial injury. Levels of postoperative cardiac troponin I were incrementally increased for each additional copy of the risk alleles of 3 single nucleotide polymorphisms: rs10116277, rs6475606, and rs2383207. Adjusted additive odds ratios ranged between 1.64 and 1.79 (asymptotic P value between 3.7 x 10(-3) and 6 x 10(-4)) and remained significantly associated with perioperative myocardial injury even after accounting for clinical covariates including severity of coronary disease, and multiple comparisons.ConclusionsWe have now demonstrated that common genetic variants in the same 9p21 locus, previously known to be associated with myocardial infarction in nonsurgical populations, are also associated with perioperative myocardial injury after coronary artery bypass grafting. Further investigation is warranted to elucidate functional mechanisms.

Dataset Information

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

Objectives

Setting

Participants

Primary and secondary outcome measures

Results

Conclusions

Publications

Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

Similar Datasets

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