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A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting.

ABSTRACT: As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral coronary artery disease (MPCAD). In this study, we genotyped COX-2 rs5275, rs5277, and rs689466 of 1544 CAD patients undergoing coronary artery bypass grafting (CABG) and found that rs5277 C allele carriage was associated with LMCAD (adjusted OR: 1.590; 95% CI: 1.103~2.291; p = 0.013). Furtherly, long-term follow-up data suggested that rs5277 C allele carriage increased risk of major adverse cardiac and cerebrovascular events (MACCE) in the whole cohort (adjusted HR: 1.561; 95% CI: 1.025~2.377; p = 0.038) and LMCAD subgroup (adjusted HR: 2.014; 95% CI: 1.036~3.913; p = 0.039) but not in MPCAD subgroup (adjusted HR: 1.375; 95% CI: 0.791~2.392; p = 0.259). In conclusion, we demonstrate that COX-2 rs5277 C allele increases the risk of left main coronary artery lesion and is also correlated with poor prognosis of LMCAD patients with CABG therapy.

SUBMITTER: Liu H

PROVIDER: S-EPMC5286485 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting.

Liu Hanning H Xu Zhengxi Z Sun Cheng C Gu Dachuan D Teng Xiao X Zhao Yan Y Zheng Zhe Z

BioMed research international 20170118

As a particular severe phenotype of coronary artery disease (CAD), left main coronary artery disease (LMCAD) is heritable. Genetic variants related to prostaglandin metabolism are associated with LMCAD. Cyclooxygenase-2 (COX-2), a key synthase in prostaglandin pathways, displays high density in atherosclerotic lesions and promotes early atherosclerosis in CAD progression. We hypothesized that genetic variants in COX-2 gene contribute to LMCAD phenotype susceptibility compared to more peripheral ...[more]

PMID: 28194409

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Project description:BackgroundCoronary artery bypass graft (CABG) surgery has traditionally represented the standard of care for left main coronary artery (LMCA) disease. However, percutaneous coronary intervention with stent implantation (PCI) has more recently emerged as a valuable alternative. The long-time awaited results of the largest randomized trials on the long-term impact of PCI versus CABG in LMCA disease, the newly published NOBLE and EXCEL studies, revealed contrasting results. Thus, aim of the present meta-analysis was to review the most robust evidence from randomized comparisons of CABG versus PCI for revascularization of LMCA.MethodsRandomized studies comparing long-term clinical outcomes of CABG or Stent-PCI for the treatment of LMCA disease were searched for in PubMed, the Chochrane Library and Scopus electronic databases. A total of 5 randomized studies were selected, including 4499 patients.ResultsNo significant difference between CABG and PCI was found in the primary analysis on the composite endpoint of death, stroke and myocardial infarction (OR = 1·06 95% CI 0·80-1·40; p = 0·70). Similarly, no differences were observed between CABG and PCI for all-cause death (OR = 1·03 95% CI 0·81-1·32; p = 0·81). Although not statistically significant, a lower rate of stroke was registered in the PCI arm (OR = 0·86; p = 0·67), while a lower rate of myocardial infarction was found in the CABG arm (OR = 1·43; p = 0·17). On the contrary, a significantly higher rate of repeat revascularization was registered in the PCI arm (OR = 1·76 95% CI 1·45-2·13; p < 0·001).ConclusionsThe present meta-analysis, the most comprehensive and updated to date, including 5 randomized studies and 4499 patients, demonstrates no difference between Stent-PCI and CABG for the treatment of LMCA disease in the composite endpoint of death, stroke and myocardial infarction. Hence, a large part of patients with unprotected left main coronary artery disease can be managed equally well by means of both these revascularization strategies.

Project description:ImportanceIn patients with left main coronary artery (LMCA) stenosis, coronary artery bypass grafting (CABG) has been the standard therapy for several decades. However, some studies suggest that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative.ObjectiveTo compare the long-term safety of PCI with drug-eluting stent vs CABG in patients with LMCA stenosis.Data sourcesPubMed, Scopus, EMBASE, Web of Knowledge, and ScienceDirect databases were searched from December 18, 2001, to February 1, 2017. Inclusion criteria were randomized clinical trial, patients with LMCA stenosis, PCI vs CABG, exclusive use of drug-eluting stents, and clinical follow-up of 3 or more years.Data extraction and synthesisTrial-level hazard ratios (HRs) and 95% CIs were pooled by fixed-effect and random-effects models with inverse variance weighting. Time-to-event individual patient data for the primary end point were reconstructed. Sensitivity analyses according to drug-eluting stent generation and coronary artery disease complexity were performed.Main outcomes and measuresThe primary end point was a composite of all-cause death, myocardial infarction, or stroke at long-term follow-up. Secondary end points included repeat revascularization and a composite of all-cause death, myocardial infarction, stroke, or repeat revascularization at long-term follow-up.ResultsA total of 4 randomized clinical trials were pooled; 4394 patients were included in the analysis. Of these, 3371 (76.7%) were men; pooled mean age was 65.4 years. According to Grading of Recommendations, Assessment, Development and Evaluation, evidence quality with respect to the primary composite end point was high. Percutaneous coronary intervention and CABG were associated with a comparable risk of all-cause death, myocardial infarction, or stroke both by fixed-effect (HR, 1.06; 95% CI, 0.90-1.24; P = .48) and random-effects (HR, 1.06; 95% CI, 0.85-1.32; P = .60) analysis. Sensitivity analyses according to low to intermediate Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (random-effects: HR, 1.02; 95% CI, 0.74-1.41; P = .89) and drug-eluting stent generation (first generation: HR, 0.90; 95% CI, 0.68-1.20; P = .49; second generation: HR, 1.19; 95% CI, 0.82-1.73; P = .36) were consistent. Kaplan-Meier curve reconstruction did not show significant variations over time between the techniques, with a 5-year incidence of all-cause death, myocardial infarction, or stroke of 18.3% (319 events) in patients treated with PCI and 16.9% (292 events) in patients treated with CABG. However, repeat revascularization after PCI was increased (HR, 1.70; 95% CI, 1.42-2.05; P < .001). Other individual secondary end points did not differ significantly between groups. Finally, pooled estimates of trials with LMCA stenosis tended overall to differ significantly from those of trials with multivessel coronary artery disease without left main LMCA stenosis.Conclusions and relevancePercutaneous coronary intervention and CABG show comparable safety in patients with LMCA stenosis and low to intermediate-complexity coronary artery disease. However, repeat revascularization is more common after PCI.

Dataset Information

A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting.

Publications

A Variant in COX-2 Gene Is Associated with Left Main Coronary Artery Disease and Clinical Outcomes of Coronary Artery Bypass Grafting.

Similar Datasets

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