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Common Variant in Glycoprotein Ia Increases Long-Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery.

ABSTRACT: This study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms.We genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T-allele carriers have a higher major adverse cardiac or cerebrovascular events risk post-CABG than those who are CC homozygotes (hazard ratio [HR]=1.29; P=0.022). The clinical association between the risk allele (T) carriage and major adverse cardiac or cerebrovascular events was confirmed in another cohort study, which included 646 CABG patients from various health centers across China. Meanwhile, rs1126643 T allele was also linked with increased risk of major adverse cardiac or cerebrovascular events (HR=1.73; P=0.019). To explore the underlying mechanisms, we prospectively recruited 131 coronary artery disease patients, assessed their platelet aggregation function, and focused on detecting their GPIA mRNA level and protein expression. Results showed that patients with rs1126643 T allele have elevated platelet aggregation activity (P=0.029) when protein expression is increased (P<0.001) and not affected by glycoprotein Ia mRNA level.The synonymous common variant, GPIA rs1126643, increases the long-term adverse events risk of CABG by augmenting GPIa protein expression and enhancing platelet aggregation function. This finding can serve as the implication of improving secondary prevention of CABG patients.

SUBMITTER: Liu H

PROVIDER: S-EPMC5210398 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Common Variant in Glycoprotein Ia Increases Long-Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery.

Liu Hanning H Xu Zhengxi Z Gu Haiyong H Li Wenke W Chen Wen W Sun Cheng C Zhao Kun K Teng Xiao X Zhang Heng H Jiang Lixin L Hu Shengshou S Zhou Zhou Z Zheng Zhe Z

Journal of the American Heart Association 20161123 12

<h4>Background</h4>This study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms.<h4>Methods and results</h4>We genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T-allele carriers have a higher major ...[more]

PMID: 27881421

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Project description:Low levels of antithrombin (AT) have been independently associated with prolonged intensive care unit stay and an increased incidence of neurologic and thromboembolic events after cardiac surgery. We hypothesized that perioperative AT activity is independently associated with postoperative major adverse cardiac events (MACEs) in patients undergoing coronary artery bypass graft (CABG) surgery.We prospectively studied 1403 patients undergoing primary CABG surgery with cardiopulmonary bypass (CPB) (http://clinicaltrials.gov/show/NCT00281164). The primary clinical end point was occurrence of MACE, defined as a composite outcome of any one or more of the following: postoperative death, reoperation for coronary graft occlusion, myocardial infarction, stroke, pulmonary embolism, or cardiac arrest until first hospital discharge. Plasma AT activity was measured before surgery, after post-CPB protamine, and on postoperative days (PODs) 1-5. Multivariate logistic regression modeling was performed to estimate the independent effect of perioperative AT activity upon MACE.MACE occurred in 146 patients (10.4%), consisting of postoperative mortality (n = 12), myocardial infarction (n = 108), stroke (n = 17), pulmonary embolism (n = 8), cardiac arrest (n = 16), or a subsequent postoperative or catheter-based treatment for graft occlusion (n = 6). AT activity at baseline did not differ between patients with (0.91 ± 0.13 IU/mL; n = 146) and without (0.92 ± 0.13 IU/mL; n = 1257) (P = 0.18) MACE. AT activity in both groups was markedly reduced immediately after CPB and recovered to baseline values over the ensuing 5 PODs. Postoperative AT activity was significantly lower in patients with MACE than those without MACE. After adjustment for clinical predictors of MACE, AT activity on PODs 2 and 3 was associated with MACE.Preoperative AT activity is not associated with MACE after CABG surgery. MACE is independently associated with postoperative AT activity but only at time points occurring predominantly after the MACE.

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.

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Common Variant in Glycoprotein Ia Increases Long-Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery.

Publications

Common Variant in Glycoprotein Ia Increases Long-Term Adverse Events Risk After Coronary Artery Bypass Graft Surgery.

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