Department of Translational Medicine, Eastern Piedmont University.
Internal Medicine, ASST Spedali Civili.
J Atheroscler Thromb. 2021 Feb 1;28(2):137-145. doi: 10.5551/jat.53405. Epub 2020 Dec 19.
Periprocedural myocardial infarction (PMI), a severe complication of Percutaneous Coronary Intervention (PCI) procedures, has a negative prognostic effect, both at short and long-term follow-up. So far, adenosine's role in preventing PMI has shown contrasting results. A genetic variant of ADORA2A receptor, 1976 C＞T, has been suggested as a potential determinant of the interindividual response to adenosine, thus conditioning its potential benefits on PMI. In our study, we investigated whether the ADORA2A 1976 C＞T polymorphism is associated with PMI occurrence in patients undergoing coronary stenting.
The study included consecutive patients undergoing PCI at the Azienda Ospedaliera-Universitaria "Maggiore della Carità," Novara, Italy, between January 2010 and January 2016. Their genetic status was assessed using polymerase chain reaction (PCR) and restriction-fragment-length-polymorphism technique. Myonecrosis biomarkers were measured at intervals from 6 to 48 hours. PMI was defined as CKMB increased 3 times over the Upper Limit of Normal (ULN), or 50% of pre-PCI value; periprocedural myonecrosis was defined as troponin I increased 3 times over the ULN or by 50% of the baseline value.
We included 1,104 patients undergoing PCI, 863 (78.2%) of whom carried the ADORA2A T-allele. No difference was found for the main demographic, clinical features, or biochemistry parameters. However, C-carriers had lower statin therapy use (p=0.008) and lower HDL-cholesterol levels (p=0.01). Homozygous C/C patients had more frequent multivessel disease (p=0.03), longer lesions (p=0.01) and Type C lesions (p=0.01), thus requiring more complex procedures. After correction for baseline confounding factors at multivariate analysis, there was no difference in myocardial necrosis according to the ADORA2A genotype (p=0.40). In contrast, PMI tended to increase in the homozygous C/C population (p=0.06), but this trend was attenuated at multivariate analysis after correction for baseline confounding factors (C/C: OR[95%CI]=1.52 [0.88-2.6], p=0.14).
Our study showed that the polymorphism rs5751876 of the ADORA2A receptor is associated with a higher prevalence of complex coronary lesions and multivessel disease. However, it does not significantly influence the occurrence of periprocedural MI or myonecrosis.
经皮冠状动脉介入治疗（PCI）过程中的围手术期心肌梗死（PMI）是一种严重的并发症，无论是在短期还是长期随访中，都具有负面的预后影响。到目前为止，腺苷在预防 PMI 中的作用显示出相互矛盾的结果。ADORA2A 受体的 1976C＞T 基因变异被认为是个体对腺苷反应的潜在决定因素，从而影响其对 PMI 的潜在益处。在我们的研究中，我们调查了 ADORA2A 1976C＞T 多态性是否与接受冠状动脉支架置入术的患者发生 PMI 有关。
本研究纳入了 2010 年 1 月至 2016 年 1 月期间在意大利诺瓦拉的 Azienda Ospedaliera-Universitaria“Maggiore della Carità”医院接受 PCI 的连续患者。使用聚合酶链反应（PCR）和限制性片段长度多态性技术评估其遗传状态。在 6 至 48 小时的时间间隔内测量肌坏死生物标志物。PMI 定义为 CKMB 升高 3 倍超过正常上限（ULN）或升高 50%基线值；围手术期肌坏死定义为肌钙蛋白 I 升高 3 倍 ULN 或升高 50%基线值。
我们纳入了 1104 名接受 PCI 的患者，其中 863 名（78.2%）携带 ADORA2A T-等位基因。主要人口统计学、临床特征或生化参数没有差异。然而，C 携带者他汀类药物使用率较低（p=0.008），HDL 胆固醇水平较低（p=0.01）。纯合 C/C 患者多发病变（p=0.03）、病变较长（p=0.01）和 C 型病变（p=0.01），因此需要更复杂的手术。在多变量分析中校正基线混杂因素后，心肌坏死与 ADORA2A 基因型无关（p=0.40）。相反，在纯合 C/C 人群中，PMI 有增加的趋势（p=0.06），但在多变量分析校正基线混杂因素后，这种趋势减弱（C/C：OR[95%CI]=1.52[0.88-2.6]，p=0.14）。
我们的研究表明，ADORA2A 受体的 rs5751876 多态性与更常见的复杂冠状动脉病变和多血管病变有关。然而，它并没有显著影响围手术期 MI 或肌坏死的发生。
