血瘀证和CYP2C19基因多态性与氯吡格雷抵抗和PCI术预后的关系

目的探讨不同程度血瘀证和CYP2C19基因多态性与氯吡格雷抵抗(CR)和经皮冠脉介入(PCI)术预后的关系。方法收集2008年1月—2009年7月连续住院的中国汉族血瘀证冠状动脉粥样硬化性心脏病(CAHD)患者415例,比较轻重程度不同血瘀证患者CYP2C19*2基因分布情况,不同程度血瘀证、CYP2C19*2(681GA)与实验室CR[LCR,即ADP诱导的最大血小板聚集率(MPA)在氯吡格雷治疗10天后比用药前下降≤10%]之间的关系,并观察择期PCI治疗术后,常规运用氯吡格雷联合阿司匹林治疗随访患者(180例)的MPA抑制率、LCR、再发心血管事件(CVEs)与血瘀证程度和CYP2C19*2基因突变之间的关系,随访7个月(中位数)。结果 (1)重度血瘀证CAHD和PCI患者681GA基因突变人数均多于轻度血瘀证患者(P0.01);(2)氯吡格雷治疗后LCR发生比率为45.06%(187/415),重度血瘀证患者LCR为61.63%(143/232),携带681A等位基因患者LCR为53.24%(115/216);(3)与轻度血瘀证CAHD患者比较,重度血瘀证CAHD患者MPA下降幅度较少(P0.01),LCR比率高(P0.01);(4)与携带CYP2C19681GG基因型CAHD患者比较,氯吡格雷治疗后,携带681A等位基因患者MPA下降幅度较少(P0.01),LCR比率高(P0.01);(5)对180例PCI术后患者随访表明,重度血瘀证和携带CYP2C19681A等位基因PCI患者不仅MPA抑制率低,LCR比率高,而且CVEs再发率高(均P0.01)。调整各项危险因素后,重度血瘀证PCI术后CVEs的危险比轻度血瘀证高(OR:4.01;95%CI:1.79-8.99);携带CYP2C19681A等位基因PCI术后CVEs的危险比GG基因型高(OR:6.89;95%CI:2.97-15.97)。结论重度血瘀证与CYP2C19*2突变不仅与CAHD患者LCR相关,而且增加PCI术后CVEs的危险。

Relationships of Blood Stasis Syndrome,CYP2C19 Gene Polymorphism with Clopidogrel Resistance and Post-PCI Prognosis

Objective To study the relationships of blood stasis syndrome （BSS）,CYP2C19 gene polymorphism with clopidogrel resistance （CR） and post-PCI prognosis.Methods Materials of 415 patients （Han nationality） with coronary atherosclerotic heart disease （CAHD） hospitalized between January 2008 and July 2009 were collected.The CYP2C192 gene distribution in patients with different degrees of BBS was observed,and the relationships of BSS,CYP2C192 with the laboratory CR [LCR,percentage of patients with ADP-induced maximal platelet aggregation （MPA） rate reduced for≤10% after a 10-day clopidogrel treatment] were analyzed.Besides,an assay on the relations of maximal platelet aggregation suppressive rate （MPAS）,LCR,recurrent cardiovascular events （RCEs） with BSS and CYP2C192 gene mutation was performed in a 7-month （in median） follow-up study on 180 post-PCI patients who received conventional treatment by clopidogrel and aspirin.Results （1） The frequency of 681GA mutation in patients with severe BSS and in those who received PCI was higher than that in those with mild BSS （P0.01）;（2） After clopidogrel treatment,LCR was 45.06% （187/415） in total patients,61.63% （143/232） in patients with severe BSS,53.24% （115/216） in patients carrying 681A allele;（3） The MPA was less decreased and the LCR was higher in patients with severe BSS than in those with mild BSS （P0.01）;（4） After clopidogrel treatment,the MPA was less decreased and the LCR was higher in carrying CYP2C19 681A allele than in those carrying 681 GG type gene （P0.01）;（5） Followup study showed that not only the MPA suppressive rate was lower,LCR was higher in patients with severe BSS or those carrying CYP2C19 681A allele,but a higher RCEs was also shown in them （P0.01）.Moreover,after the various risk factors had been adjusted,the RCEs in patients with severe BSS or carrying CYP2C19 681A allele was higher than in those with mild BSS （OR：4.01;95% CI：1.79-8.99） or carrying GG type gene （OR：6.89;95% CI：2.97-15.97）.Conclusion Severe BSS and CYP2C192 gene mutation are associated with LCR,and could increase the risk of postPCI cardiovascular events recurrence in patients with CAHD.