| Coronary artery bypass grafting(CABG)is one of the main therapies of coronary artery disease(CAD),especially for severe CAD patients with left main(LM)lesions,multi-vessel diseases,diabetes mellitus,and left ventricular dysfunction.CABG has the best efficacy among the main therapies for CAD,still,death,myocardial infarction,stroke and repeat revascularization in the long-term run after CABG bothers both surgeons and patients.According to reports,the occurrence of major adverse cardiac and cerebrovascular events(MACCE)would be 11.8%?31.0%.To predict the long-term risk after CABG is very important for the optimization of secondary prevention and improvement of prognosis after CABG.This study compared three common-used clinical variable-based evaluation score systems of risk after CABG,and assessed the efficiency of the score systems for predicting the long-term adverse events.We found out that these three systems were not good enough for the evaluation of long-term risk after CABG.To improve the predicting of prognosis after CABG,we then introduced genetic variables to establish a single nucleotide polymorphisms(SNP)-based genetic risk score(GRS),assessed the efficiency of GRS and compared GRS with clinical variable based scores.We concluded that GRS had higher values on the predicting of long-term risk after CABG.In addition,we explored the underlying mechanisms of one associated SNP-GPIA rs1126643.Finally,we studied one of the severe kind of CAD-left main disease(LMCAD),and found out a genetic common variant in COX-2 gene(COX-2 rs5277)was associated with the occurrence of LMCAD and the prognosis of CABG for LMCAD patients.Part?Study on the score system based on single nucleotide polymorphisms for the long-term prognosis after CABG.Backgrounds-Severe clinical variables-based score systems were established to evaluated short-term prognosis after CABG,and long-term clinical-based score systems were also used to evaluate risk after CABG in Western patients.However,how well these score systems perform for predicting long-term risk after CABG among Chinese patiens were unkown.This part of study was aimed to assess the efficiency of three common clinical variables-based score system for predicting long-term risk after CABG in Chinese patients,and established a genetic-based score system to predict long-term risk after CABG in Chinese patients.Methods and results-Cox proportional regression model was used to study the association of score systems and long-term MACCE,C-index under Cox model,Hosmer-Lemeshow statistic,IDI and NRI was used to evaluate the efficiency of different models.The hazard ration under Cox model of EuroSCORE was 1.066(95%CI:1.001?1.136,p=0.048),of SinoSCORE was 1.052(95%CI:1.016?1.088,p=0.004),of NYScore was 1.078(95%CI:1.032?1.126,p=0.001).All the three models showed strong association with long-term MACCE.However,All the three models have limited ability to predict long-term MACCE.Among all the adverse events after CABG,the efficacy of predicting all cause death after CABG was best:C-index of EuroSCORE was 0.629(95%CI:0.574?0.684,p<0.001),of SinoSCORE was 0.629(95%CI:0.564?0.684,p<0.001),of NYScore was 0.646(95%Cl:0.591?0.701,p<0.001).SinoSCORE has acceptable ability on long-term MI and repeat revascularization predicting,the C-index was 0.613(95%CI:0.513?0.713,p=0.031)and 0.601(95%CI:0.532?0.670,p=0.006).Using survival analysis,we found out that IL-6R rs1800796(HR=1.268,95%CI:1.083?1.483,p=0.003),GPIArs1126643(HR=1.277,95%CI:1.081?1.508:,p=0.004),THBD rs1042579(HR=1.225,95%CI:1.031?1.455,p=0.021),P2RY12 rs2046934(HR=1.236,95%CI:1.022?1.494,p=0.029)and CYP2C19 rs4244285(HR=1.185,95%CI:1.008?1.392,p=0.040)were associated with long-term MACCE after CABG.Based on these five single nucleotide polymorphisms,we established a genetic risk score to predict long-term MACCE after CABG,and the predicting ability of genetic risk score was better than clinical-based score systems.Then we also used C-index,Hosmer-Lemeshow statistic,IDI and NRI to study whether combination of genetic risk score and clinical risk score can improve the efficiency of MACCE predicting,and we proved that combine genetic risk score and clinical risk score can achiev the best efficacy.Conclusions-In conclusion,the efficiency for long-term MACCE predicting of clinical-based score was not good enough,and it was of necessity to set up new model of long-term model of long-term MACCE after CABG among Chinese patients.We established the genetic risk score and found that this score system has highest efficacy to predict long-term MACCE and combination of genetic factors and clinical factors can be used to improvent the ability of long-term MACCE predicting.This part of study proved that genetic risk score has the potential to be used for secondary prevention and avoiding adverse events.Part ?Study on the association and underlying mechanisms of GPIA rs1126643 polymorphism and the long-term adverse events after CABGBackgrounds-This study was aimed to investigate the clinical relevance between GPIA rsl 126643C/T polymorphism and the outcome of CAD after coronary artery bypass graft(CABG)surgery and to explore the involved potential mechanisms.Methods and results-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(MACCE)risk after CABG than patients who are CC homozygotes(HR=1.29,p=0.022).The clinical association between the risk allele(T)carriage and MACCE 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 MACCE(HR=1.735 p=0.019).To explore the underlying mechanisms,we prospectively recruited 131 CAD patients,assessed their platelet aggregation function,and focused on detecting their GPIA mRNA level and protein expression.Results showed that the patients with rs1126643 T allele have elevated platelet aggregation activity(p=0.029)when the protein expression is increased(p<0.001),and not affected by the glycoprotein la mRNA level.Conclusions-The synonymous common variant GPIA rsl 126643 increases the long-term adverse events risk of CABG by augmenting the GPIa protein expression and enhancing the platelet aggregation function.This finding can serve as the implication of improving secondary prevention of CABG patients.Part ?Study on the association of single nucleotide polymorphism in COX-2 gene and left main coronary artery disease and the prognosis after CABGBackgrounds-As a particularly severe phenotype of coronary artery disease(CAD),left main coronary artery disease(LMCAD)is heritable.Genetic variants related to prostaglandin metabolism is 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).Methods and Results-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;pp=0.013).Furtherly,long-term follow-up data suggested 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).Conclusions-In conclusion,we demonstrate 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. |
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