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[血瘀证、CYP2C19基因多态性与氯吡格雷抵抗及经皮冠状动脉介入治疗后预后的关系]

[Relationships of blood stasis syndrome, CYP2C19 gene polymorphism with clopidogrel resistance and post-PCI prognosis].

作者信息

Chen Hui, Yan Wei, Wu Xiao-ying

机构信息

Provincial Clinical College of Fujian Medical University, Fujian Provincial Institute of Cardiovascular Disease, Fuzhou 350001.

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010 Dec;30(12):1245-9.

Abstract

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 < or = 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 CYP2C19*2 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 681G>A mutation in patients with severe BSS and in those who received PCI was higher than that in those with mild BSS (P<0.01); (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 (P<0.01); (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 (P<0.01); (5) Follow-up 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 (P<0.01). 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 CYP2C19*2 gene mutation are associated with LCR, and could increase the risk of post-PCI cardiovascular events recurrence in patients with CAHD.

摘要

目的

研究血瘀证(BSS)、CYP2C19基因多态性与氯吡格雷抵抗(CR)及经皮冠状动脉介入治疗(PCI)后预后的关系。

方法

收集2008年1月至2009年7月住院的415例汉族冠心病(CAHD)患者资料。观察不同程度BSS患者的CYP2C192基因分布,分析BSS、CYP2C192与实验室CR[LCR,氯吡格雷治疗10天后二磷酸腺苷(ADP)诱导的最大血小板聚集(MPA)率降低≤10%的患者百分比]的关系。此外,对180例接受氯吡格雷和阿司匹林常规治疗的PCI术后患者进行了为期7个月(中位时间)的随访研究,分析最大血小板聚集抑制率(MPAS)、LCR、心血管事件复发(RCEs)与BSS和CYP2C19*2基因突变的关系。

结果

(1)重度BSS患者及接受PCI患者的681G>A突变频率高于轻度BSS患者(P<0.01);(2)氯吡格雷治疗后,总患者LCR为45.06%(187/415),重度BSS患者为61.63%(143/232),携带681A等位基因患者为53.24%(115/216);(3)重度BSS患者的MPA降低幅度小于轻度BSS患者,LCR高于轻度BSS患者(P<0.01);(4)氯吡格雷治疗后,携带CYP2C19 681A等位基因患者的MPA降低幅度小于携带681 GG型基因患者,LCR高于携带681 GG型基因患者(P<0.01);(5)随访研究表明,重度BSS患者或携带CYP2C19 681A等位基因患者不仅MPA抑制率较低、LCR较高,而且RCEs也较高(P<0.01)。此外,在调整各种危险因素后,重度BSS患者或携带CYP2C19 681A等位基因患者的RCEs高于轻度BSS患者(比值比:4.01;95%可信区间:1.79-8.99)或携带GG型基因患者(比值比:6.89;95%可信区间:2.97-15.97)。

结论

重度BSS和CYP2C19*2基因突变与LCR相关,可增加CAHD患者PCI术后心血管事件复发风险。

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