Department of Cardiology, Charité Berlin - University Medicine, Campus Benjamin Franklin and Berlin Institute of Health (BIH), Hindenburgdamm 30, 12203 Berlin, Germany.
Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland.
Eur Heart J. 2017 Feb 14;38(7):511-515. doi: 10.1093/eurheartj/ehw563.
MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS).
In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up. From a miRNA profiling in a matched derivation case-control cohort, 14 miRNAs were selected for validation. Comparing 63 cases vs. 126 controls, 3 miRNAs were significantly differentially abundant. In patients with MACE, miR-26b-5p levels (P = 0.038) were decreased, whereas miR-320a (P = 0.047) and miR-660-5p (P = 0.01) levels were increased. MiR-26b-5p has been suggested to prevent adverse cardiomyocyte hypertrophy, whereas miR-320a promotes cardiomyocyte death and apoptosis, and miR-660-5p has been related to active platelet production. This suggests that miR-26b-5p, miR-320a, and miR-660-5p may reflect alterations of different pathophysiological pathways involved in clinical outcome after ACS. Consistently, these three miRNAs reliably discriminated cases from controls [area under the receiver-operating characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683, and miR-320a =0.672]. Combination of the three miRNAs further increased AUC to 0.718. Importantly, addition of the three miRNAs to both, the Global Registry of Acute Coronary Events (GRACE) score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement of 0.20 in both cases.
This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI.
微小 RNA（miRNA）是重要的非编码调控因子，可控制基因表达模式。然而，在急性冠状动脉综合征（ACS）患者中，尚未对与不良心血管结局相关的循环 miRNA 水平进行分析和验证。
在一项多中心前瞻性 ACS 队列研究中，2168 例患者中有 1002 例表现出 ST 段抬高型心肌梗死（STEMI）。63 例 STEMI 患者在 1 年的随访中发生了经裁决的主要心血管不良事件（MACE，定义为心脏死亡或复发性心肌梗死）。在匹配的推导病例对照队列中进行 miRNA 分析后，选择了 14 个 miRNA 进行验证。比较 63 例病例与 126 例对照，有 3 个 miRNA 差异显著。在发生 MACE 的患者中，miR-26b-5p 水平（P=0.038）降低，而 miR-320a（P=0.047）和 miR-660-5p（P=0.01）水平升高。miR-26b-5p 已被建议可预防不良的心肌细胞肥大，而 miR-320a 可促进心肌细胞死亡和凋亡，miR-660-5p 与血小板的活跃生成有关。这表明 miR-26b-5p、miR-320a 和 miR-660-5p 可能反映了 ACS 后与临床结局相关的不同病理生理途径的变化。一致地，这三个 miRNA 可以可靠地区分病例和对照 [年龄和性别调整 Cox 回归中的 miR-26b-5p 的受试者工作特征曲线（AUC）=0.707，miR-660-5p=0.683，miR-320a=0.672]。三种 miRNA 的组合进一步将 AUC 提高至 0.718。重要的是，将三种 miRNA 添加到全球急性冠状动脉事件注册（GRACE）评分和临床模型中，将 AUC 从 0.679 分别提高到 0.720 和 0.722，两种情况下的净重新分类改善均为 0.20。
这是第一项在 STEMI 患者中进行 miRNA 与不良心血管结局相关分析和验证的研究。miR-26b-5p、miR-320a 和 miR-660-5p 可区分 MACE，并在添加到 GRACE 评分和临床模型后增加风险预测。这些发现表明，特定 miRNA 释放到循环中可能反映了对 STEMI 后临床结局有影响的分子途径的激活。
