Dataset Information

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

ABSTRACT: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery.We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703).Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.

SUBMITTER: Podgoreanu MV

PROVIDER: S-EPMC1945056 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

Podgoreanu M V MV White W D WD Morris R W RW Mathew J P JP Stafford-Smith M M Welsby I J IJ Grocott H P HP Milano C A CA Newman M F MF Schwinn D A DA

Circulation 20060701 1 Suppl

<h4>Background</h4>The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery.<h4>Methods and results</h4>We genotyped 48 polym ...[more]

PMID: 16820586

Similar Datasets

Project description:ObjectiveThe objective of this study was to develop and to validate the Vascular Quality Initiative (VQI) Cardiac Risk Index (CRI) for prediction of postoperative myocardial infarction (POMI) after vascular surgery.MethodsWe developed risk models for in-hospital POMI after 88,791 nonemergent operations from the VQI registry, including carotid endarterectomy (CEA; n = 45,340), infrainguinal bypass (INFRA; n = 18,054), suprainguinal bypass (SUPRA; n = 2678), endovascular aneurysm repair (EVAR; n = 18,539), and open abdominal aortic aneurysm repair (OAAA repair; n = 4180). Multivariable logistic regression was used to create an all-procedure and four procedure-specific risk calculators based on the derivation cohort from 2012 to 2014 (N = 61,236). Generalizability of the all-procedure model was evaluated by applying it to each procedure subtype. The models were validated using a cohort (N = 27,555) from January 2015 to February 2016. Model discrimination was measured by area under the receiver operating characteristic curve (AUC), and performance was validated by bootstrapping 5000 iterations. The VQI CRI calculator was made available on the Internet and as a free smart phone app available through QxCalculate.ResultsOverall POMI incidence was 1.6%, with variation by procedure type as follows: CEA, 0.8%; EVAR, 1.0%; INFRA, 2.6%; SUPRA, 3.1%; and OAAA repair, 4.3% (P < .001). Predictors of POMI in the all-procedure model included age, operation type, coronary artery disease, congestive heart failure, diabetes, creatinine concentration >1.8 mg/dL, stress test status, and body mass index (AUC, 0.75; 95% confidence interval [CI], 0.73-0.76). The all-procedure model demonstrated only minimally reduced accuracy when it was applied to each procedure, with the following AUCs: CEA, 0.65 (95% CI, 0.59-0.70); INFRA, 0.69 (95% CI, 0.64-0.73); EVAR, 0.72 (95% CI, 0.65-0.80); SUPRA, 0.62 (95% CI, 0.52-0.72); and OAAA, 0.63 (95% CI, 0.56-0.70). Procedure-specific models had unique predictors and showed improved prediction compared with the all-procedure model, with the following AUCs: CEA, 0.69 (95% CI, 0.66-0.72); INFRA, 0.75 (95% CI, 0.73-0.78); EVAR, 0.76 (95% CI, 0.73-0.80); and OAAA, 0.72 (95% CI, 0.69-0.77). Bias-corrected AUC (95% CI) from internal validation for the models was as follows: all procedures, 0.75 (0.73-0.76); CEA, 0.68 (0.65-0.71); INFRA, 0.74 (0.72-0.76); EVAR, 0.73 (0.70-0.78); and OAAA repair, 0.68 (0.65-0.73).ConclusionsThe VQI CRI is a useful and valid clinical decision-making tool to predict POMI after vascular surgery. Procedure-specific models improve accuracy when they include unique risk factors.

Project description:The aim of this study is to assess for regional variation in the incidence of postoperative myocardial infarction (POMI) following nonemergent vascular surgery across the United States to identify potential areas for quality improvement initiatives.We evaluated POMI rates across 17 regional Vascular Quality Initiative (VQI) groups that comprised 243 centers with 1,343 surgeons who performed 75,057 vascular operations from 2010 to 2014. Four procedures were included in the analysis: carotid endarterectomy (CEA, n = 39,118), endovascular abdominal aortic aneurysm (AAA) repair (EVAR, n = 15,106), infrainguinal bypass (INFRA, n = 17,176), and open infrarenal AAA repair (OAAA, n = 3,657). POMI was categorized by the method of diagnosis as troponin-only or clinical/ECG and rates were investigated in regions with ?100 consecutive cases. Regions with significantly different POMI rates were defined as those >1.5 interquartile lengths beyond the 75th percentile of the distribution. Risk-adjusted rates of POMI were assessed using the VQI Cardiac Risk Index all-procedures prediction model to compare the observed versus expected rates for each region.Overall rates of POMI varied by procedure type: CEA 0.8%, EVAR 1.1%, INFRA 2.7%, and OAAA 4.2% (P < 0.001). Significant variation in POMI rates was observed between regions, resulting in differing ranges of POMI rates for each procedure: CEA 0.5-2.0% (P = 0.001), EVAR 0.3-3.1% (P < 0.001), INFRA 1.1-4.8% (P < 0.001), and OAAA 2.2-10.0% (P < 0.001). A single region in 3 of the 4 procedure-specific datasets was identified as a statistical outlier with a significantly higher POMI rate after CEA, EVAR, and OAAA; this region was identical for the EVAR and OAAA datasets but was a different region for the CEA dataset. No significant variation in POMI was noted between regions after INFRA. Procedure-specific clinical POMI rates (mean; range) were significantly different between regions for EVAR (0.4%; 0-1.1%, P = 0.01) and INFRA (1.4%; 0.5-2.9%, P = 0.01), but not for CEA (0.4%; 0-0.8%, P = 0.53) or OAAA (1.6%; 0-3.8%, P = 0.23). Procedure-specific troponin-only POMI rates (mean; range) were significantly different between regions for all procedures: CEA (0.4%; 0.1-1.2%, P < 0.001), EVAR (0.7%; 0-2.1%, P < 0.001), INFRA (1.3%; 0.4-2.5%, P = 0.001), and OAAA (2.5%; 0-8.5%, P < 0.001). After risk adjustment, regional variation was again noted with 3 regions having higher and 4 regions having lower than expected rates of POMI.Significant variation in POMI rates following major vascular surgery exists across VQI regions even after risk adjustment. These findings may present an opportunity for focused regional quality improvement efforts.

Dataset Information

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

Publications

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets