| Background and Objective As an anti-platelet drug,clopidogrel is recommended as Class I in the diagnosis and treatment guidelines for coronary heart disease(CHD)at home and abroad,and studies have confirmed its exact role in the prevention and treatment of coronary heart disease.However,clinical observations of some patients with oral administration of clopidogrel according to the doctor’s orders,chest pain,chest tightness and other angina symptoms did not significantly improve,some patients undergoing invasive interventional examination prompted coronary artery stenosis site increased or in the stent platelet adhesion After the formation of thrombosis or stent intimal hyperplasia caused by restenosis,leading to myocardial ischemia and hypoxia increased,and even acute myocardial infarction.The occurrence of these conditions suggests that the antiplatelet effect of clopidogrel after absorption and metabolism is weakened or basically ineffective.Based on this situation,scholars proposed the concept of "Clopidogrel Resistance(CR)".Although there is still no clear systematic description of clopidogrel resistance mechanisms,a number of studies have indicated that clopidogrel resistance is associated with gene polymorphisms involved in drug absorption,metabolism,and excretion of liver drug enzymes,among which cytochrome P450 2C19(ie,CYP2C19)plays a pivotal role in the two-step metabolism of clopidogrel.The relationship between CYP2C19 genotype and CR is relatively close.As one of the risk factors for coronary heart disease,the risk of coronary heart disease is higher in patients with hypertension.Related studies have suggested that there is a certain correlation between essential hypertension with certain genetic background andCYP2C19 gene.By bridging these genes,resistance to clopidogrel may be inextricably linked to coronary heart disease patients with hypertension.The main purpose of this study was to observe the distribution of CYP2C19 genotype polymorphisms and the presence of CR in patients with coronary heart disease and hypertension without coronary heart disease,and thus to further verify the association of coronary heart disease patients with clopidogrel.Whether the resistance is related or not provides theoretical evidence for the physicians to treat anti-platelet drugs in the clinical treatment of coronary heart disease patients with hypertension.Materials and Methods 2016.12 to 2017.5 Coronary angiography(CAG)of the Department of Cardiology at the An-Tex First Affiliated Hospital diagnosed 104 patients with CHD and was divided into coronary heart disease group with hypertension(CHD group with hypertension),56 cases.)and coronary heart disease group without hypertension(CHD group without hypertension,48 cases),oral routine dose of clopidogrel 75 mg/day,aspirin combined with 100 mg/day,rest of the treatment such as expansion of the coronary artery,lipid stabilization Plaques,blood circulation,and other drugs are basically the same in both groups.Five milliliters of venous blood were collected on the next day of admission and 5 days after administration,and the platelet inhibition rate was measured.At the same time,2 ml of blood was collected from peripheral veins on the next morning.The CYP 2C19 genotypes were detected by gene chip technology.The distribution characteristics and mutations of different(wild and mutant)genotypes of CYP2C19 in CHD patients with hypertension and CHD without hypertension were observed.The proportion of patients with the type of gene and their corresponding CR status were analyzed at the same time as the correlations between baseline data,hypertension,CYP2C19 genotype and multiple dependent variables and CR.Results The study found that: 1.Based on the analysis of whether or not patients with coronary artery disease were grouped after combined hypertension,there was no statistically significant difference in the distribution of different metabolic genotypes of clopidogrel CYP2C19 between the two groups(P=0.135,P>0.05);2.Incidence of CR in CHD group with hypertension and CHD without hypertension,also no significant difference in statistics(P=0.236,P>0.05);3.Polymorphism in CYP2C19 gene In grouping,the incidence of clopidogrel resistance was lower in the slow metabolizing group(also known as the weak metabolome group)and the intermediate metabolizing group in patients with fast metabolizing genome(also known as the strong metabolome group),and the difference was statistically significant(P<0.05).The incidence of CR in slow metabolizing group was significantly higher than that in fast metabolizing group;4.Logistic multiple regression analysis of CHD patients with hypertension showed that CYP2C19 genotype could be an independent risk factor for the prediction of clopidogrel resistance.Conclusion 1.The distribution of CYP2C19 gene polymorphisms and the corresponding incidence of CR in patients with coronary heart disease have nothing to do with the merger of hypertension,coronary heart disease patients with hypertension in the clinical course of treatment may not require targeted antiplatelet drug adjustment.2.CR and CYP2C19 gene polymorphisms are closely related,in which fast metabolizing gene patients have relatively low rates of CR in metabolizers and metabolizers.For patients with coronary heart disease who need to be treated with clopidogrel,clinicians can The CYP2C19 genotype was screened for high-risk individuals with CR,adjusted for individualization of antiplatelet drugs and relatively reasonable prognosis. |
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