Division of Prevention Community Health, National Center for Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences.
Heart Center and Beijing Key Laboratory of Hypertension, Chaoyang Hospital, Capital Medical University.
Circ J. 2020 Jun 25;84(7):1155-1162. doi: 10.1253/circj.CJ-19-1181. Epub 2020 May 13.
Circulating microRNAs (miRNA) are potential prognostic biomarkers for cardiovascular disease. We aimed to identify serum miRNA as an effective predictor for coronary artery disease (CAD) events in a general population cohort.
Serum miRNAs associated with CAD were determined by small RNA sequencing and quantitative RT-PCR. Further, the predictive ability of identified serum miRNAs was measured in a general population of 2,812 people. As a main outcome measure, CAD events were collected for 6 years and included acute myocardial infarction and subsequent myocardial infarction. Out of the 48 miRNA candidates, 5 miRNAs (miR-10a-5p, miR-126-3p, miR-210-3p, miR-423-3p and miR-92a-3p) showed better reliability and repeatability in serum. Then, the association of serum levels of the 5 miRNAs with CAD was validated. Furthermore, miR-10a-5p and miR-423-3p, which showed better performance, were tested in the large cohort, with a median follow up of 6.0 years. In multivariable Cox regression analysis, only miR-423-3p (P for trend<0.001) was able to precisely predict CAD events. Moreover, the addition of circulating miR-423-3p with the traditional risk factors together markedly improved the various model performance measures, including the area under the operating characteristics curve (0.782 vs. 0.806), Akaike Information Criterion (965.845 vs. 943.113) and net reclassification improvement (19.18%).
Circulating miR-423-3p can improve the prediction of primary CAD outcomes on the basis of a traditional risk factor model in general population.
循环 microRNA（miRNA）是心血管疾病的潜在预后生物标志物。我们旨在确定血清 miRNA 是否可作为一般人群队列中冠心病（CAD）事件的有效预测因子。
通过小 RNA 测序和定量 RT-PCR 确定与 CAD 相关的血清 miRNA。此外，在 2812 人的一般人群中测量了鉴定出的血清 miRNA 的预测能力。主要观察指标为 6 年 CAD 事件，包括急性心肌梗死和随后的心肌梗死。在 48 个 miRNA 候选物中，有 5 个 miRNA（miR-10a-5p、miR-126-3p、miR-210-3p、miR-423-3p 和 miR-92a-3p）在血清中具有更好的可靠性和可重复性。然后，验证了血清中 5 种 miRNA 水平与 CAD 的相关性。此外，在大队列中进一步检测了表现更好的 miR-10a-5p 和 miR-423-3p，中位随访时间为 6.0 年。多变量 Cox 回归分析显示，只有 miR-423-3p（趋势 P<0.001）能够准确预测 CAD 事件。此外，将循环 miR-423-3p 与传统危险因素联合应用可显著提高各种模型性能指标，包括工作特征曲线下面积（0.782 比 0.806）、Akaike 信息准则（965.845 比 943.113）和净重新分类改善（19.18%）。
循环 miR-423-3p 可以在一般人群中基于传统危险因素模型改善原发性 CAD 结局的预测。
