高危急性冠脉综合征病人经皮冠状动脉支架植入术术后发生氯吡格雷抵抗的相关因素及预后分析

Influencing factors of high risk ACS patients with low clopidogrel response after percutaneous coronary intervention and the effect on the prognosis

目的探讨高危急性冠脉综合征(ACS)病人经皮冠状动脉支架植入术(PCI)术后对P2Y12受体拮抗剂抑制血小板聚集的反应性及影响因素,同时在此基础上探讨对病人预后的影响。方法 86例ACS行PCI术病人,分为氯吡格雷抵抗(CR)组24例,无氯吡格雷抵抗(NCR)组62例。运用焦磷酸测序技术,检测其CYP2C19*2,*3单核苷酸多态性及二磷酸腺苷(ADP)诱导的血小板聚集率,分析病人CR与基因型的关系。经Logistic回归分析CR的影响因素,并对病人进行1年的心脏不良事件(MACE)、卒中、呼吸困难、出血事件的随访。结果单因素及Logistic回归分析表明,野生基因型(OR=0.15,P=0.011,95%CI=0.04~0.67)是CR的保护因素;而高血压病史(P=0.021,OR=8.136,95%CI=1.48~44.80)、空腹血糖值(P=0.012,OR=1.51,95%CI=1.10~2.06)、基础血小板聚集率(P=0.023,OR=1.06,95%CI=0.01~1.11)等3个因素是CR的危险影响因素;此外,术后1年随访,总MACE发生率CR组为29.2%,明显高于NCR的9.7%。结论 CYP2C19基因型与CR引发的心血管事件有重要关联。CYP2C19野生型基因是高危ACS病人发生CR的保护因素;高血压病史、高空腹血糖值、血小板高反应性为CR的危险因素,CR组病人PCI术后MACE事件显著增高。CYP2C19*2,*3是CR发生的独立预测因子,CR作为独立危险因素,预示着心血管事件发生的危险增加。

Objective To observe the reactivityand the influential factors of clopidogrel resistance in high risk patients with coronary heart disease after percutaneous coronary intervention （PCI ） . Methods A total of 86 patients who were treated with aspirin and clopi-dogrel after PCI were enrolled,the CYP2C19 ＊ 2, ＊ 3 single nucleotide polymorphisms were detected by the technology of pyrosequenc- ing,and adenosine monophosphate （ ADP） -induced platelet aggregation ratewas detectedby optical heterometry method. The general bas-ic data,biochemical parameters and imaging characteristics were compared between two groups,and the independent predictors of clopi- dog resistance were confirmed by Logistic regression analysis. Results Single factor analysis and Logistic regression model showed thatWild-type of CYP2C19 （ OR =0. 15 = 0. 011,95% CI = 0. 04-0. 67） was the protective factor of CR, while hypertension history（P = 0. 021,OR =8. 136,95% CI = 1.48^14. 80） ,fasting plasma glucose（ P =0. 012, OR = 1. 51,95% CI = 1. 10-2. 06） , basic ADP- induced platelet aggregation rate （ P = 0. 023 , OR = 1 .0 6 ,95% CI = 0. 01 -1. 11） were risk factors of CR. Postoperative follow-up showed that total MACE incidence in CR was 20. 2% , significantly higher than 9.7% in NCR group. Conclusions Wild-type of CYP2C19 was protective factor of CHD patients with CR. Heterozygous-type was a risk factor for CHD patients with CR. The mutation of single nucleotide polymorphism at the site ＊ 2 and ＊ 3 of CYP2C19 gene may increase the risk of MACE of patients with PCI. Diabe-tes, the high platelet activation level and high blood pressure might be risk factors of CR in patients with CHD after PCI.