细胞色素P4502 C19快代谢基因型缺血性卒中患者氯吡格雷抵抗的影响因素分析

目的 探讨细胞色素P4502C19(CYP2C19)快代谢基因型缺血性卒中患者氯吡格雷抵抗的影响因素.方法 回顾性连续纳入CYP2C19快代谢基因型(CYP2C19*1/*1)缺血性卒中住院患者204例,均于确诊后连续服用氯吡格雷75 mg/d,共7 d,第8天晨起空腹抽取静脉血,2 h内完成血栓弹力图血小板图的检测....

Analysis of risk factors for clopidogrel resistance in ischemic stroke patients with cytochrome P4502C19 extensive metabolic genotype

Objective To investigate risk factors for clopidogrel resistance in ischemic stroke patients with cytochrome P4502C19(CYP2C19)extensive metabolic genotype.Methods A total of 204 ischemic stroke patients treated with clopidogrel with CYP2C19 extensive metabolic genotype(CYP2C19*1/*1)were enrolled retrospectively.Continuously administration of clopidogrel 75 mg daily for 7 days after diagnosis,fasting venous blood was extracted on the morning of the 8th day,and thrombelastogram was performed within 2 hours.Platelet inhibition rate<30%induced by adenosine diphosphate(ADP)was defined as clopidogrel resistance,and platelet inhibition rate≥30%as clopidogrel non-resistance,respectively.All of patients were divided into clopidogrel resistant group and clopidogrel non-resistant group according to platelet inhibition rate.The baseline data(age,gender,past medical historyhypertension,hyperlipidemia,diabetes mellitus,coronary heart disease])and laboratory test indexes(blood routine,glycosylated hemoglobin,liver and kidney function,blood lipid,uric acid,homocysteine,etc.)were compared.Clopidogrel resistance was taken as the dependent variable and risk factors with P<0.05 were selected as independent variables through univariate analysis for multivariate Logistic regression analysis.Results(1)All 204 ischemic stroke patients with CYP2C19 extensive metabolic genotype(CYP2C19*1/*1)were divided into clopidogrel resistant group(n=65 cases)and clopidogrel non-resistant group(n=139 cases).The incidence of clopidogrel resistance was 31.9%.The proportion of female,hypertension and the level of white blood cell count in the clopidogrel resistant group was higher than that in the clopidogrel non-resistant group,with significant differences between the two groups(33.8%22/65]vs.20.9%29/139],χ²=3.981;70.8%46/65]vs.55.4%77/139],χ²=4.372;7.2±1.6]×109/L vs.6.7±1.4]×109/L,t=2.220;all P<0.05).Age,hyperlipidemia,diabetes mellitus,coronary heart disease,platelet count,glycosylated hemoglobin,alanine aminotransferase,fasting glucose,triacylglycerine,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,uric acid and homocysteine between two groups had no statistically significant difference(all P>0.05).(2)Binary Logistic regression analysis showed that female(OR,2.115,95%CI 1.066-4.196,P=0.032),history of hypertension(OR,2.196,95%CI 1.138-4.237,P=0.019)and high level of white blood cell count(OR,1.253,95%CI 1.016-1.545,P=0.035)were independent risk factors for clopidogrel resistance.Conclusion Female gender,hypertension and high level of white blood cell count can increase the risk of clopidogrel resistance in ischemic stroke patients with CYP2C19 extensive metabolic genotype.