Gager Gloria M, Eyileten Ceren, Postula Marek, Gasecka Aleksandra, Jarosz-Popek Joanna, Gelbenegger Georg, Jilma Bernd, Lang Irene, Siller-Matula Jolanta
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Front Cardiovasc Med. 2022 Jul 8;9:948006. doi: 10.3389/fcvm.2022.948006. eCollection 2022.
MicroRNAs (miRNA, miR) have an undeniable physiological and pathophysiological significance and act as promising novel biomarkers. The aim of the study was to investigate blood-derived miRNAs and their association with long-term all-cause mortality in patients with multivessel disease (MVD) suffering from acute coronary syndrome (ACS).
This study was an observational prospective study, which included 90 patients with MVD and ACS. Expression of miR-125a, miR-125b, and miR-223 was analysed by polymerase chain reaction (PCR). Patients were followed-up for a median of 7.5 years. All-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events.
Elevated expression of miR-125b (>4.6) at the time-point of ACS was associated with increased long-term all-cause mortality (adjusted [adj.] hazard ratio [HR] = 11.26, 95% confidence interval [95% CI]: 1.15-110.38; = 0.038). The receiver operating characteristic (ROC) analysis showed a satisfactory c-statistics for miR-125b for the prediction of long-term all-cause mortality (area under the curve [AUC] = 0.76, 95% CI: 0.61-0.91; = 0.034; the negative predictive value of 98%). Kaplan-Meier time to event analysis confirmed an early separation of the survival curves between patients with high vs low expression of miR-125b ( = 0.003). An increased expression of miR-125a and miR-223 was found in patients with non-ST-segment elevation ACS (NSTE-ACS) as compared to those with ST-segment elevation myocardial infarction (STEMI) ( = 0.043 and = 0.049, respectively) with no difference in the expression of miR-125b between the type of ACS.
In this hypothesis generating study, lower values of miR-125b were related to improved long-term survival in patients with ACS and MVD. Larger studies are needed to investigate whether miR-125b can be used as a suitable predictor for long-term all-cause mortality.
微小RNA（miRNA，miR）具有不可忽视的生理和病理生理意义，有望成为新型生物标志物。本研究旨在调查急性冠状动脉综合征（ACS）合并多支血管病变（MVD）患者血液中的miRNA及其与长期全因死亡率的关系。
本研究为观察性前瞻性研究，纳入90例MVD合并ACS患者。采用聚合酶链反应（PCR）分析miR-125a、miR-125b和miR-223的表达。对患者进行了中位时间为7.5年的随访。将全因死亡率视为主要终点。采用校正Cox回归分析预测事件发生情况。
ACS时miR-125b表达升高（>4.6）与长期全因死亡率增加相关（校正[adj.]风险比[HR]=11.26，95%置信区间[95%CI]：1.15-110.38；P=0.038）。受试者工作特征（ROC）分析显示，miR-125b对长期全因死亡率的预测具有良好的c统计量（曲线下面积[AUC]=0.76，95%CI：0.61-0.91；P=0.034；阴性预测值为98%）。Kaplan-Meier事件发生时间分析证实，miR-125b高表达和低表达患者的生存曲线早期分离（P=0.003）。与ST段抬高型心肌梗死（STEMI）患者相比，非ST段抬高型ACS（NSTE-ACS）患者中miR-125a和miR-223表达增加（分别为P=0.043和P=0.049），不同类型ACS患者的miR-125b表达无差异。
在这项探索性研究中，较低的miR-125b水平与ACS合并MVD患者的长期生存率提高相关。需要开展更大规模的研究来调查miR-125b是否可作为长期全因死亡率的合适预测指标。
