Correlation Study Between Clopidogrel Resistance And Recurrence Of Ischemic Stroke And Gene Polymorphism

Part 1 Recurrence of ischemic stroke and clopidogrel resistance:Correlation Study.Objective:To discuss the relationship between clopidogrel resistance and recurrence of cerebral ischemic stroke,and to explore the factors related to the recurrence of cerebral infarction.Methods:From June 2017 to August,61 patients with acute ischemic stroke hospitalized in the neurology department of the second hospital of Hebei Medical University were treated with clopidogrel.After 7 days,platelet function was detected,and they were divided into clopidogrel sensitive(CS)group and clopidogrel resistance(CR)group.All patients discharged were asked to continue to take clopidogrel and were followed up for half a year.Remove the patients with drug-replacement and irregular oral-clopidogrel.According to the follow-up results of the primary endpoint,the patients were divided into recurrent and non recurrent cerebral infarction group.The cilnical data of the two groups:age,sex,hypertension,diabetes,coronary heart disease,smoking,alcohol consumption,triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),homocysteine(HCY)and others were compared.And compared the recurrence of cerebral infarction between CS group and CR group.Results:1.There were 22 people in group CS and 39 in group CR.According to the follow-up results,there were 9 cases of recurrent group and 37 cases in the non recurrent group except for the excluded ones.In group CS,there were 0recurrent cerebral infarction,1 of cerebral hemorrhage.And in group CR,there were 9 patients with recurrent cerebral infarction and 1 for non fatal myocardial infarction.2.Comparing with non recurrent group,the proportionof the history of heart disease in group of recurrent cerebral infarction is higher(44.4%to5.4%),and the difference was statistically significant(c~2=6.59,P=0.01).There was no significant difference of the general clinical data between two groups.(P>0.05).3.The recurrence rate of cerebral infarction in group CR(37.5%)was significantly higher than that in group CS(0%)(P<0.05).Part 2 Correlation study of CYP2C19 and ABCB1 gene polymorphisms with clopidogrel resistance in cerebral ischemic strokeObjective:To detect the genetic polymorphisms of CYP2C19*2(681G>A),CYP2C19*3(636G>A)and ABCB1(3435C>T),to analysis the correlation of them with CR and recurrence of cerebral infarction,and to discuss the influencing factors of CR.Methods:From June 2017 to August,61 patients with acute ischemic stroke hospitalized in the neurology department of the second hospital of Hebei Medical University were treated with clopidogrel.After 7 days,platelet function was detected,and they were divided into clopidogrel sensitive(CS)group and clopidogrel resistance(CR)group.The general clinical data of group CS and CR were compared.By Snapshot gene sequencing,a total of 58patients received 3 gene locus’polymorphism detection,and they were divided into wild type,heterozygous type and homozygous type.The correlation between CYP2C19 and ABCB1 gene polymorphisms and CR was analyzed.All patients discharged were asked to continue to take clopidogrel and were followed up for half a year.Remove the patients with drug-replacement and irregular oral-clopidogrel.The relationship between gene polymorphism and recurrence of cerebral infarction was observed.*1/*1is defined as the normal metabolic type(NM);*1/*2 or*1/*3 are defined as intermediate metabolic type(IM);*2/*3,*2/*2 and*3/*3 are defined as slow metabolism type(PM),and analysis wether there are differences between the3 metabolic kinds of CR and of the recurrence of cerebral infarction.Results:1.There were 22 people in group CS and 39 in group CR.A comparison of general clinical data in these two groups showed that age,sex and smoking may have an impact on CR(P<0.05).Age was the independent risk factor of CR after Logistic regression(OR=1.087,95%CI=1.012-1.168,P<0.05).2.The mutation rate of CYP2C19*2 locus was 53.45%,the mutation rate of CYP2C19*3 site was 5.17%,and there was no homozygous mutation at this locus,and the mutation rate of ABCB1(3435C>T)was 72.41%.Among the 3loci,there was no significant difference in the distribution of genotypes between the CS group and the CR group(P>0.05).3.It was found that the proportion of CR in slow metabolic type(80%)was higher than that in normal metabolic type(62.5%)and intermediate metabolic type(65.52%),but there was no significant difference between the 3groups(P>0.05).4.After follow-up,there were 9 patients had recurrent cerebral infarction and 37 patients had no recurrence,and of which 43 were tested by snapshot.In the 3 locus,there was no significant difference of the recurrence of cerebral infarction between the 3 genotypes(P>0.05).5.Of the 3 metabolic types,the recurrence of cerebral infarction were 4(21.1%),5(21.7%)and 0(0),respectively.There was no significant difference between the groups(P>0.05).Part 3 Correlation study of atorvastatin dose and clopidogrel resistanceObjective:To observe whether clopidogrel resistance and atorvastatin dose were related.Methods:From June 2017 to August in the second hospital of Hebei Medical University,patients of acute ischemic stroke were treated with Clopidogrel Bisulfate Tablets 75mg/d,Atorvastatin Calcium Tablets 40mg/d oral treatment.platelet function was detected.Asked all discharged patients with CR continue to take Clopidogrel Bisulfate Tablets 75mg/d,Atorvastatin Calcium Tablets 20mg/d.After 2 weeks,the platelet function test was reviewed.The results of two platelet aggregation rates was compared.Results:There was no significant difference of MAR before and after the reduction of the dose of atorvastatin in 15 CR patients(P>0.05).Conclusion:1.There are some patients of cerebral infarction with CR,and the recurrence rate of cerebral infarction in CR patients is high.The history of heart disease may affect the recurrence of cerebral infarction.2.Age,sex,and smoking may have impacts on CR.Among them,age is an independent risk factor for CR.3.The mutation rates of CYP2C19*2(681G>A)and ABCB1(3435C>T)were high,and the mutation rate of CYP2C19*3(636G>A)was low.There was no significant correlation between the mutation of the 3 loci and CR and the recurrence of cerebral infarction.4.CR may not be related to the dose of atorvastatin.