| Background:Acute myocardial infarction(AMI)is the leading cause of death worldwide and it accounts for more than 50 percent mortality of cardiovascular disease(CVD)in China.Recently,Chinese incidence and mortality of AMI has been rising gradually,especially in young adults.Percutaneous coronary intervention(PCI)is the primary treatment for AMI and is more effective in reducing mortality and adverse events compared with medications.Clopidogrel is an anti-platelet drug used by approximately 40 million patients worldwide to treat or prevent atherothrombotic events after PCI.However,about 4-30%of the patients treated with clopidogrel display no or an insufficient anti-platelet response.This phenomenon is called clopidogrel resistance or clopidogrel non-responsiveness(CR).Many studies have indecate that CYP2C19 loss-of-function polymorphisms may be the main mechanism of CR,which encode not fully-function enzymes to transform clopidogrel into active metabolite.Previous studies have investigated the relationship between CYP2C 19*2 and CYP2C 19*3 loss-of-function polymorphisms and clinical prognosis in CVD patients undergoing PCI and treated with clopidogrel,but the outcomes were inconsistent.However,most studies involved either foreigners or elders Chinese counterparts.Datas just concerning Chinese AMI young adults(?40 years)are in shortage and urgent demand.This study aims to determine the effect of CYP2C19a*2 and CYP2C19*3 loss-of-function polymorphisms on the platelet activity and the occurrence of adverse clinical events in Chinese AMI adults younger than40 years old,as well as on Qi deficiency and blood stasis syndrome diagnosing by Traditional Chinese Medicine(TCM).We also investigate the risk factors for serious AMI in more young AMI adults in China.Objective:1.To investigate the risk factors for serious AMI of young adults in China.2.To determine the effect of CYP2C19*2 and CYP2C19*3 loss-of-function polymorphism s on the platelet activity and clinal prognosis in Chinese AMI adults younger than 40 years old.3.To find the relationship between CYP2C19*2 and CYP2C19*3 loss-of-funct ion polymorphisms and qi deficiency and blood stasis syndrome diagnosing by TCM i n young AMI adults(?40)after PCI.Methods:This is a prospective cohort study.AMI young adults(?40 years)treated in Fuwai hospital were consecutively enrolled between 2012-01-01 and 2016-12-01.Part 1.Amount to 732 young AMI patients were classified into 2 groups determined by serious AMI diagnose.Serious AMI is defined as large area myocardial infarction.The risk factors for serious MI were analyzed.Part 2.A total of 122AMI patients with drug-eluting stent and treated with clopidogr el after successfully PCI were enrolled and divided into 2 groups,as normal metaboli zers--extensive metabolizers(EMs),and weak metabolizers--intermediate and slow metab olizers(IMs,PMs),according to the CYP2C19 genotype.The ADP-induced platelet inh ibition rate was measured by thrombo-elastography(TEG).The relationships between CYP2C19 genotype and ADP inhibition rate 24-72 hours after PCI,as well as main a dverse cardiovascular events(MACEs)within 18 months after the procedure,were analy zed between 2 groups.The MACE were recoded as cardiac death,non-fatal MI,early stent thrombosis(ST)and coronary revascularization.Part 3.57 patients out of above 122 patients were separated into 2 groups depending on with Qi deficiency and blood stasis syndrome or not.The relationships between Qi deficiency and blood stasis syndrome and CYP2C19 genotype,as well as ADP inhib ition rate within 24-72 hours after PCI,were analyzed between the 2 groups.Results:1.Smoking more than 15 years(OR=1.862,CI:1.351?2.567,P<0.001),rising h igh-sensitivity C reactive protein(Hs-CRP)(OR=1.034,CI:1.000-1.070,P=0.047)were ind ependent risk factors for serious AMI in young adults younger than 40 years old.2.The CR/HTPR rate in patients of the normal metabolizers and weak metabolizers were respectively 26.9%and 24.3%,(P=0.741).The cumulative 18-month incidence of primary clinical end point events in patients of the normal metabolizers and weak metabolizers were 7.69%and 22.86%(P=0.032)and the composite ones were respectively 17.3%and 32.86%(p=0.028).3.Survival analysis of Kaplan-Meier curves showed that the survival rates of the major metabolic events(EMs)were significantly lower in the weak metabolic group(PMs and IMs)than that in the normal metabolic group(MACE),and the difference was statistically significant.(Log-rank,P = 0.021).However,multivariate analysis indicated that there is no independent causal association of CYP2C19 loss-of-function allele carriage with MACE(P=0.215).4.The weak metabolizers in the qi deficiency and blood stasis syndrome group and the control group were respectively 16(82.6%)and 19(41.7%),p=0.007.The ADP-induced inhibition rate were respectively 77.93 ± 31.33 and 75.35 ± 25.60(P=0.360).The difference of CR/HTPR between the two groups was not statistically significant(P=0.561).Conclusion:l.Smoking more than 15 years,rising Hs-CRP increase the risk for seriou s AMI in young adults younger than 40 years old.2.CYP2C19 genotype is insufficient evidence for accurate prediction of CR and progn osis in AMI patients younger than 40 years.3.The Qi deficiency and blood stasis syndrome is associates with CYP2C19*2 and CYP2C19*3 loss-of-function polymorphisms and these patients had increase risk in adverse prognosis. |
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