| BackgroudCoronary heart disease(CHD)is a kind of disease which seriously threatens human health and leads to death in the contemporary society,Among them,acute coronary syndrome(ACS)is characterized by acute onset,rapid change of disease and severe disease.ACS is based on coronary atherosclerosis due to endothelial injury and unstable plaque rupture secondary cause platelet adhesion,activation and aggregation,coagulation and fibrinolysis system disequilibrium cause thrombosis,and strong vascular spasm leads to the emergence of a series of clinical symptoms.Thrombosis is an important factor in the occurrence and development of acute coronary syndrome,and anticoagulation and antiplatelet therapy are the cornerstone of its treatment.Currently,the combined use of clopidogrel and aspirin is the most classic antiplatelet therapy,clopidogrel is platelet ADP receptor antagonist,which is needed in the liver of cytochrome P450(CYP)enzyme metabolism to become active metabolites,while CYP2C19 gene enzyme which is one of cytochrome P450(CYP)enzyme play a most important influence in the clopidogrel drug efficacy.The use of clopidogrel antiplatelet therapy in patients with coronary heart disease,due to the existence of individual differences,some patients have recurrent episodes of myocardial ischemia,myocardial infarction and other serious adverse cardiovascular events in clopidogrel treatment process,considering the existence of clopidogrel resistance can,and the study found the increased probability of adverse cardiovascular events in patients with clopidogrel resistance.There are many factors that influence clopidogrel resistance,and the present study shows that genetic factors play a key role.Now,more and more research attention the CYP2C19 gene polymorphism,the aim of this study were to analysis the patients with acute coronary syndrome CYP2C19 gene polymorphisms distribution and clinical characteristics,and to evaluate the ralationship between CYP2C19 gene polymorphisms curative effect of clopidogrel and short-term adverse cardiovascular events,provide evidence for clinical treatment.AimThrough the detection of CYP2C19 gene polymorphism of ACS patients,clinical data collection,analysis of the distribution of different CYP2C19 genotype metabolism,clinical characteristics,and to evaluate the ralationship between CYP2C19 gene polymorphisms curative effect of clopidogrel and short-term adverse cardiovascular events,provide evidence for clinical treatment.MethodsMethods a total of 341 patients who were admitted to the Department of Cardiology of Guangzhou No.1 People’s Hospital affiliated to Guangzhou Medical University from December 2015 to February 2017 were selected as the subjects of the study.The all patients were diagnosed with ACS and treated with in parallel with percutaneous coronary intervention(PCI).The patients with ACS according to CYP2C19 gene metabolic type divided into fast metabolism group(including CYP2C19 *1/*1),middle metabolism group(including CYP2C19 *1/*2,CYP2C19 *1/*3)and slow metabolism group(including CYP2C19 *2/*2,CYP2C19 group *2/*3,CYP2C19,*3/*3),and fast metabolism group 133 cases(including 95 male and 38 female),middle metabolic group 169 cases(including 114 male and 55 female)and slow metabolism group 39 cases(including 29 male and 10 female).Comparison of three groups in aspects like general clinical materials(including ages,gender,smoking,hypertension,diabetes,body mass index and so on),blood biochemical index,coronary artery stenosis and the number of lesions,the number of sents,gensini score,inhibition of platelet aggregation,clopidogrel resistance,the occurrence of major adverse cardiovascular events in hospitalization.Logistic regression was used to analyze the risk factors of clopidogrel resistance and major adverse cardiovascular events.Rusults1.The distribution of CYP2C19 genotype in 341 patients with ACS was in accordance with the Hardy-Weinberg genetic equilibrium(P>0.05),and the samples were representative;The metabolic type of CYP2C19 gene was the highest in the middle metabolism group(49.6%),fast metabolism group ranked second(39.0%),slow metabolism group had the lowest percentage(11.4%).CYP2C19 *1,CYP2C19 *2,CYP2C19 *3 allele frequencies were 63.8%,31.4%,4.8%;CYP2C19 genotypes *1/*1,*1/*2,*1/*3,*2/*2,*2/*3,*3/*3 accounted for 39.0%,41.9%,7.6%,9.7%,1.5% and 0.3%.2.Three different groups of CYP2C19 gene metabolic phenotype of patients at risk factors of coronary heart disease(age,gender,smoking,diabetes,hypertension,hyperlipidemia,BMI),ACS(STEMI,NSTEMI,UA),vital signs(systolic blood pressure,diastolic blood pressure,heart rate),auxiliary examination(white blood cell,hemoglobin,platelet,blood creatinine,high sensitivity C-reactive protein,uric acid,total cholesterol,triglyceride,high density lipoprotein cholesterol,low density lipoprotein cholesterol,homocysteine,glycosylated hemoglobin,left ventricular ejection fraction,left ventricular end diastolic diameter),coronary angiography and PCI results(stenosis degree,lesion number,the number of stent implantation and the Gensini score),no statistical significance in comparison of clinical data(P > 0.05).3.The use of thrombelastogram for inhibition of platelet aggregation assay,CYP2C19 gene fast metabolism group,middle metabolism group and slow metabolism group platelet inhibition rates were 66.40±21.28%、53.64±24.75%、46.82±21.95%,variance analysis showed that between the three groups was statistically significant(P< 0.05),group and the group comparison shows that fast metabotropic group and middle metabolism group and slow metabolism group has statistical significance(P<0.05);but between the middle metabolism group and slow metabolism were not statistically significant(P>0.05);4.The inhibition rate of platelet aggregation less than 30% was defined as clopidogrel resistance,341 cases of ACS patients with a total of 109 cases of clopidogrel resistance(31.96%).wherein the fast metabolism group,meddle metabolism group and slow metabolism group were accounted for 22 cases(16.5%),67 cases(39.6%),20 cases(51.3%).The occurrence of clopidogrel resistance as the dependent variable for two multi factor classification logistic regression analysis showed that the middle metabolic group(OR=3.22,95%CI:1.814~5.716,P=0.000)and slow metabolism group(OR=6.071,95%CI:2.692~13.688,P=0.000)may be the independent risk factors of clopidogrel resistance occurred.5.The three group of CYP2C19 genotype was the single event during the period of hospitalization(death,heart failure,malignant arrhythmia,target vessel revascularization,stent thrombosis,hemorrhage)and total MACE was not statistically significant,the single event and total MACE Logistic regression analysis showed that systolic blood pressure at admission and the normal hemoglobin is to protect total MACE events;systolic blood pressure at admission was a protective factor of malignant arrhythmia,and male patients are risk factors;admission age,high BMI,high uric acid,the number of blood vessels of coronary artery disease are risk factors for heart failure,and hemoglobin,creatinine were the protective factors.However,there was no significant correlation between CYP2C19 genotype and single event or total MACE events.Comlusions1.The CYP2C19 genotype of the patients with ACS was the most in the middle metabolic group,the second in the fast metabolic group,and the lowest in the slow metabolism group;2.The CYP2C19 gene in the middle metabolic groups and slow metabolic groups increased risk of clopidogrel resistance;3.The study finds that the higher systolic pressure and normal hemoglobin were the protective factors for total MACE in hospital,while CYP219 genotypes was not related to total MACE.4.The study finds that the high systolic pressure is a protective factor for malignant arrhythmia,while male patients are the risk factor.The risk factors for heart failure include old ages,high BMI,high uric acid and the number of diseased blood vessels,while hemoglobin and normal creatinine are the protective factors.However,there was no significant correlation between CYP219 genotype and single MACE. |
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