基于ACE基因多态性探讨冠心病患者支架术后心血管事件发生风险

    Risk exploration of cardiovascular events after coronary stent implantation in patients with coronary heart disease: a study based on ACE gene polymorphisms

    • 摘要:
      目的 探讨血管紧张素I转换酶(ACE)基因插入/缺失(I/D)基因多态性与冠心病患者支架术后心血管事件发生风险的关系。
      方法 本研究为2021年1月~2022年3月在武汉市中西医结合医院进行的单中心队列研究。对象为接受急诊或择期冠状动脉支架植入术的冠心病患者,并在植入后使用氯吡格雷和阿司匹林双重抗血小板治疗,持续至少1年。对患者随访12个月。使用TaqMan分析对ACE I/D进行基因分型。通过光透射聚集测定法评估血小板聚集。主要不良心血管事件(MACE)定义为心血管死亡、心肌梗死和缺血性卒中的复合事件。
      结果 在随访期间,共有44例患者出现MACE,包括15例心源性死亡、16例非致死性心肌梗死和13例缺血性卒中。与未发生MACE的患者相比,发生MACE的患者年龄更大,左心室射血分数降低比例更高,诊断为稳定型心绞痛例数更少和ST段抬高急性心肌梗死例数更多(均P<0.01)。与无MACE组相比,MACE组II基因型与DD基因型比例低,ID基因型+DD基因型比例高(均P<0.05)。进行COX回归分析,模型根据临床协变量进行了调整,调整模型包括年龄、既往心肌梗死、高血压、糖尿病、左心室射血分数、血清肌酐、诊断、低密度脂蛋白、吸烟状况和既往经皮冠状动脉介入治疗。各类型基因型比较,ID或DD基因型患者的MACE风险是II基因型患者的1.99倍(调整模型中校正HR:1.99,95% CI:1.00~3.98,P<0.05)。ID基因型患者发生MACE的风险是II基因型患者的2.13倍(调整模型中校正HR:2.13;95%CI:1.10~4.12,P<0.05),而DD和II基因型之间的MACE风险无显著差异。与II基因型相比,基线的和1个月的ID或DD基因型患者血小板反应性百分数值升高;与ID基因型相比,基线的和1个月的DD基因型患者血小板反应性百分数值升高,均P<0.01。
      结论 ACE I/D基因多态性(rs4646994)中ID基因型与PCI支架植入术后患者1年随访时心血管风险增加相关,ID或DD与血小板反应性百分数值升高有关。

       

      Abstract:
      AIM To investigate the relationship between the insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme (ACE) gene and the risk of cardiovascular events in patients with coronary heart disease after stent implantation.
      METHODS This was a single-center cohort study conducted in our hospital from January 2021 to March 2022. The inclusion criteria were patients with coronary heart disease who received emergency or elective coronary stent implantation and were treated with clopidogrel 75 mg and aspirin 100mg once a day for at least one year after implantation. The patients were followed up for 12 months. ACE I/D was genotyped by TaqMan analysis and platelet aggregation was evaluated by light transmission aggregation assay. Major cardiovascular adverse events (MACE) were defined as compound events of cardiovascular death, myocardial infarction and ischemic stroke.
      RESULTS During the follow-up period, a total of 44 patients experienced MACE, including 15 cases of cardiac death, 16 cases of non fatal myocardial infarction, and 13 cases of ischemic stroke. Compared with patients who did not experience MACE, patients who experienced MACE were older, had more cases of decreased left ventricular ejection fraction, fewer cases of diagnosed stable angina, and more cases of ST segment elevation acute myocardial infarction (all P<0.01). Compared with the non MACE group, the MACE group had a lower proportion of genotype II and DD, and a higher proportion of genotype ID and DD (both P<0.05). Cox regression analysis was conducted, and the model was adjusted according to clinical covariates, including age, previous myocardial infarction, hypertension, diabetes, left ventricular ejection fraction, serum creatinine, diagnosis, low-density lipoprotein, smoking status, and previous percutaneous coronary intervention. The MACE risk of patients with ID or DD genotype is 1.99 times higher than that of patients with II genotype compared to different genotypes (adjusted for HR: 1.99, 95% CI: 1.00~3.98, P<0.05). The risk of MACE in patients with ID genotype is 2.13 times higher than that in patients with II genotype (adjusted for HR: 2.13; 95% CI: 1.10~4.12, P<0.05), while there is no significant difference in MACE risk between DD and II genotypes. Compared with genotype II, baseline and 1-month ID or DD genotype patients had higher platelet reactivity percentage values; Compared with the ID genotype, the percentage of platelet reactivity in baseline and 1-month DD genotype patients increased, all P<0.01.
      CONCLUSIONS The ID genotype in ACE I/D gene polymorphism (rs4646994) is associated with increased cardiovascular risk at 1-year follow-up in patients after PCI stent implantation, and ID or DD is associated with increased platelet reactivity percentage values.

       

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