摘要
目的：分析冠状动脉粥样硬化性心脏病（冠心病）患者行经皮冠状动脉介入术（ PCI）后1年和15年内再次发生不良心血管事件的相关因素。方法1998年1月至2013年3月在北京医院心内科行 PCI 术或同时行冠状动脉搭桥术、病历资料完整并接受氯吡格雷和阿司匹林双联抗血小板治疗1年的冠心病患者纳入本研究。取患者静脉血进行与氯吡格雷代谢有关的细胞色素 P450（CYP）2C19基因型检测，并据此将患者分为正常代谢型组（＊1/＊1）、中间代谢型组（＊1/＊2和＊1/＊3）和慢代谢型组（＊2/＊2、＊2/＊3和＊3/＊3），回顾性分析患者 PCI 术后1年内和首次 PCI 术后15年内再发不良心血管事件的情况与相关因素。结果共纳入210例患者，男性148例，女性62例；年龄49-84岁，平均（67±10）岁；行首次 PCI 术者163例，行2次 PCI 术者47例；单独行 PCI 术者185例，同时行冠状动脉搭桥术者25例。合并高血压、高脂血症和糖尿病者分别为158、156和91例。正常代谢型组、中间代谢型组和慢代谢型组 PCI 术后1年内不良心血管事件发生率分别为13.3%（13/98）、24.7%（23/93）和31.6%（6/19），慢代谢型组和中间代谢型组的发生率分别是正常代谢型组的2.37倍和1.86倍。携带 CYP2C19＊2或＊3等位基因是 PCI 术后1年内发生不良心血管事件的独立危险因素[比值比（OR）=1.781，95%置信区间（CI）：1.042-3.046，P =0.035），适量饮白酒是不良心血管事件的防护因素（OR =0.054，95% CI：0.175-1.016，P =0.045）。正常代谢型组、中间代谢型组和慢代谢型组首次 PCI 术后15年内不良心血管事件发生率分别为32.7%（32/98）、33.3%（31/93）和36.8%（7/19），3组间差异无统计学意义。合并糖尿病（OR =3.243、95% CI：1.245-5.165，P 〈0.05）和有冠心病家族史（OR =2.683，95% CI：1.232-5.359，P =0.006）是 PCI 术后15年内发生不良心血管事件的独立危险因素。结论携带 CYP2C19＊2或＊3等位基因是冠心病患者 PCI 术后1年内再发不良心血管事件的独立危险因素，合并糖尿病和有冠心病家族史是 PCI 术后15年内再发不良心血管事件的独立危险因素。建议准备行 PCI 术或新近行 PCI 术的冠心病患者检测 CYP2C19基因型，并根据检测结果决定是否采用氯吡格雷抗血小板治疗。
Objective To analyze the influential factors for recurrent adverse cardiovascular events within one year and 15 years after percutaneous coronary intervention（ PCI）in patients with coronary atherosclerotic heart disease（CHD）. Methods The patients with CHD,who underwent PCI or bypass operation of coronary artery meanwhile in Department of Cardiology,Beijing Hospital from january 1998 to March 2013,had complete medical records and received dual antiplatelet therapy with clopidogrel and aspirin for one year,were enrolled in the study. Patients＇ specimens of blood were collected and cytochrome P450 （CYP）2C19 genotype associated with metabolism of clopidogrel were detected. The patients were divided into the reference metabolizers group（ ＊1 / ＊1）,intermediate metabolizers group（ ＊1 / ＊2 and ＊1 / ＊3）and slow metabolizers group（ ＊2 / ＊2,＊2 / ＊3 and ＊3 / ＊3）by the results of genotype detection. The situation of recurrent adverse cardiovascular events within one year and 15 years after the first PCI and the correlative factors were analyzed retrospectively. Results A total of 210 patients were enrolled in the study. They comprised of 148 males and 62 females with age 49-84（67 ± 10）years. There were 163 and 47 patients undergoing PCI for the first and second times,respectively. There were 185 and 25 patients undergoing PCI only and bypass operation of coronary artery meanwhile,respectively. There were 158,156,and 91 cases complicated with hypertension,hyperlipoidemia,and diabetes,respectively. The incidence of adverse cardiovascular events in the reference metabolizers group,the intermediate metabolizers group,and the slow metabolizers group within one year after PCI were 13. 3%（13 / 98）,24. 7%（23 / 93）,and 31. 6%（6 /19）,respectively. The incidence of adverse cardiovascular events in the slow metabolizers group and the intermediate metabolizers group were 2. 37 and 1. 86 times of those in the reference metabolizers group, respectively. Carrying CYP2C19＊2 or ＊3 genotype was the independent risk factor（OR = 1. 781,95% CI：1. 042-3. 046,P = 0. 035）and moderate drinking of white spirit was the independent protection factor （OR = 0. 054,95% CI：0. 175-1. 016,P = 0. 045）in adverse cardiovascular events within one year after PCI. The incidence of adverse cardiovascular events in the reference metabolizers group,the intermediate metabolizers group,and the slow metabolizers group within 15 years after PCI were 32. 7% （32 / 98）, 33. 3%（ 31 / 93 ）,and 36. 8% （ 7 / 19 ）,respectively,the differences among the 3 groups were not statistically significant. Combination with diabetes（OR = 3. 243,95% CI：1. 245-5. 165,P 〈 0. 05）and with familial history of CHD（OR = 2. 683,95% CI：1. 232-5. 359,P = 0. 006）were the independent risk factors in adverse cardiovascular events within 15 years after PCI. Conclusions Carrying CYP2C19＊2 or＊3 genotype is the risk factor in recurrent adverse cardiovascular events in patient with CHD within one year after PCI. Combination of diabetes and with familial history of CHD are the risk factors in recurrent adverse cardiovascular events within 15 years after PCI. It is suggested that the patients who prepare to perform PCI or have performed PCI recently should detect the CYP2C19 genotype and decide whether or not to receive the antiplatelet therapy with clopidogrel by the results of genotype detection.
出处
《药物不良反应杂志》
CSCD
2014年第6期350-355,共6页
Adverse Drug Reactions Journal
关键词
经皮冠状动脉介入术
细胞色素
P450
酶系统
多态性
基因
心血管事件
Percutaneous coronary intervention
Cytochrom P-450 enzyme system
Polymorphism,genetic
Adverse cardiovascular events
