| Part 1Comparison of Long Term Outcome of Chinese Patients with Premature Triple Vessel Coronary Disease Among Three Treatment StrategiesBackgroundCoronary artery disease(CHD)is a quite common cardiovascular disorder that threatens public health worldwide,which has become prevalent in young and middle-age individuals.CHD in young and middle-age individuals was referred as premature coronary heart disease(PCHD).The incidence of PCHD is gradually increased including triple-vessel disease.PCHD patients possess high potential progress of coronary atherosclerosis and relatively longer expectancy of life,that make them expose to a higher risk of recurrent coronary events.Therefore,it is important to choose the appropriate treatment strategy for patients with premature triple-vessel disease.Revascularization therapy in PCHD patients is associated with lower procedural risk.For premature TVD patients,the evidence of revascularization strategy derived from some small sample studies,so that the optimal treatment remains controversial.However,there is no data comparing long-term clinical outcomes among different treatment modalities,including coronary artery bypass grafting(CABG),percutaneous coronary intervention(PCI)and medical therapy(MT)alone in patients with premature TVD.The long-term efficacy of these three treatment strategies is not clear.ObjectThe aim of this study is to compare the long-term effectiveness and safety among coronary artery bypass grafting(CABG),percutaneous coronary intervention(PCI)and medical therapy alone in patients with premature coronary triple-vessel disease.MethodThis study consecutively enrolled patients in Fuwai hospital(Beijing,China)from April 2004 to February 2010,who underwent coronary angiography and diagnosed as coronary triple-vessel disease.The age standard definition of premature coronary heart disease was:male?50 and female?60 years old.The patients were divided into three groups according to the different treatment strategies,including coronary artery bypass grafting group,percutaneous coronary intervention group and medical therapy group.All patients completed a median 83 months follow-up.One-way ANOVA test,chi square test and Kaplan-Meier method was applied to evaluate the primary end point:all-cause mortality;secondary end points:cardiac death,main adverse cardiovascular and cerebrovascular events(MACCE),recurrent myocardial infarction,nonfatal stroke or repeat revascularization.Cox proportional-hazards regression was expressed by hazard ratios(HR)together with corresponding 95%confidence intervals,in order to compare long-term outcomes among groups.Subgroup analysis was performed for different populations.ResultsPCI,CABG and MT alone were performed in 933(52.1%),459(25.6%)and 400(22.3%)patients respectively.Both PCI and CABG were associated with lower all-cause mortality versus MT alone(4.6%vs.4.1%vs.15.5%,p<0.0001),as well as cardiac death(2.8%vs.2.0%vs.9.8%,p<0.0001),and there was no difference between PCI and CABG group.The incidence of myocardial infarction and repeat revascularization in CABG group were significantly lower than PCI and MT group,respectively(4.4%vs.9.8%vs.4.5%,p=0.0001)and(4.6%vs.16.0%vs.11.3%,p<0.0001).However,there was no difference among these three groups with stroke(4.0%vs.6.8%vs.5.8%,p=0.07).After adjustment of baseline factors,CABG and PCI were associated with lower risk of all-cause mortality versus MT alone(HR:0.35,95%CI:0.18-0.69,p =0.003;HR:0.35,95%CI:0.23-0.53,p<0.0001),and there was no difference between PCI and CABG group,so did cardiac death.CABG patients had a lower incidence of myocardial infarction and repeat revascularization compared with PCI or MT.There was no significantly difference on stroke among three groups.Compared with CABG and MT group,the average SYNTAX score was lower in PCI group(PCI group 21.7±7.7 vs.CABG group 29.6±9.0 vs.MT alone group 24.7 ± 10.2,p<0.0001).The proportion of patients with LM disease in group PCI was 8.2%,which was significantly lower than that in CABG group(31.8%)and MT group(16.5%).ConclusionAmong patients with premature TVD,PCI and CABG both achieved satisfactory and comparable long-term benefits.CABG was associated with lower risk of myocardial infarction and repeat revascularization,without increased risk of stroke.Patients received MT alone was associated with worst long-term clinical outcomes.It should choose the appropriate revascularization strategy according to the complexity of coronary artery lesions and SNYTAX score.Part 2Association of Genetic Variants with Premature Coronary Triple Vessel DiseaseBackgroundCoronary heart disease(CHD)is a complex multi-factorial disease,and the genetic factors of CHD have always been the focus of researchers.In recent years,a series of gene variants which related to CHD had been identified by genome-wide association studies.CHD in young and middle-age individuals was referred as premature coronary heart disease(PCHD).Previous studies suggested that genetic factors gave a greater impact on PCHD.However,it is not clear about the role of genetic factors in premature coronary triple vessel disease(PTVD).Combined with previous literatures and Chinese genome-wide association study(GWAS)of CHD patients,the associated genes of Chinese premature coronary triple vessel disease were speculated,including guanylate cyclase 1 soluble subunit alpha(GUCY1A3),CDKN2B antisense RNA 1(CDKN2B-AS1),phosphatase and actin regulator 1(PHACTR1),transcription factor 21(TCF21),and ADAM metallopeptidase with thrombospondin type 1 motif 7(ADAMTS7)gene.It is not clear of the association between the polymorphisms of these genes and premature coronary triple vessel disease Chinese patients.ObjectiveTo found the possible genetic mutations of Chinese premature coronary triple vessel disease,and provide a theoretical basis for the process of genetic factors in the occurrence and development of premature coronary heart disease.Find a feasible target for individual diagnosis and therapy with premature coronary heart disease patients.MethodsThis study consecutively enrolled patients in Fuwai hospital(Beijing,China)from April 2004 to February 2010,who underwent coronary angiography and diagnosed as coronary triple-vessel disease.The age standard definition of premature coronary heart disease was:male?50 and female?60 years old.Healthy control group without coronary artery disease was selected at the same time.There were 37 tag SNPs selected from GUCY1A3,CDKN2B-AS1,PHACTR1,TCF21,and ADAMTS7 genes,which were detected by the ligase detection reaction.Genome-wide association study(GAWS)of China Han population and research literature about coronary heart disease related genes of foreign expert were consulted.Tag SNPs were selected by the HapMap database of China Han population.The first 200 patients in each group were sent to preliminary experiment,then using chi square test to analysis the results of tag SNPs.Secondly,sent the residual samples for test,and found the clear correlation between positive tag SNPs and premature triple-vessel disease.ResultsA total of 37 tag SNPs of the 5 genes were detected in the preliminary experiment.The mutation allele frequencies of 7 tag SNPs from the CDKN2B-AS1 gene of 9p21.3 were significantly higher in group of premature triple-vessel disease(PTVD)compared with control group,respectively,rs1063192(p=0.009);rs10757274(p=0.006);rs1333042(p=0.01);rs1333049(p=0.04);rs3217986(p=0.01);rs4977574(p=0.004);rs9632884(p=0.01).In the official test,9 tag SNPs of CDKN2B-AS1 gene were sent to detect.It showed that the mutation allele frequencies of 7 tag SNPs were significantly higher in PTVD group compared with the control group,respectively,rs1063192(Gp<0.001);rs10757274(G p=0.001);rs1333042(A p<0.001);rs1333049(C p<0.001);rs2285327(Cp=0.034);rs3217992(T p=0.045);rs4977574(G p=0.003);rs9632884(G p<0.001).After FDR BH correction,the p values still had statistically different between the groups.Conclusion1.Several mutations in CDKN2A-AS1 gene from 9p21.3 were associated with premature triple-vessel disease in china.2.The mutation of CDKN2A-AS1 gene in Chinese population is an important genetic basis for premature triple-vessel disease.3.CDKN2A-AS1 gene polymorphism is not only involved in the occurrence of premature coronary heart disease,but may also be related to the severity of coronary artery disease in patients with premature coronary heart disease. |
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