Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients
Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients
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DOI：
10.1002/ejhf.984
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发表时间：
2018-01-01
影响因子：
18.2
通讯作者：
Pinto, Yigal M.
中科院分区：
文献类型：
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作者：
Bayes-Genis, Antoni;Lanfear, David E.;Pinto, Yigal M.
小型研究表明，循环microRNAs （miRNAs）可作为心力衰竭（HF）的生物标志物。然而，测量循环mirna的标准化方法和质量评估并没有统一建立，而且大多数研究都是小规模的，因此结果不一致。我们使用了标准化的数据处理方案，优化了循环miRNA qpcr来去除噪声，并使用它来评估哪些循环miRNA有力地增加了心衰患者的预后信息。方法和结果我们在两个独立的队列共2203名受试者中测量了12种mirna。队列1（巴塞罗那）包括834例慢性心衰患者。队列II（底特律）包括1369名慢性心衰患者。每个样本一式两份测量，并归一化为非常丰富和稳定的miRNA （miR-486-5p）。我们使用多步算法来区分错误的放大信号，从而将每个miRNA测量分为“有效”，“不可检测”或“无效”。在两个队列中，较高水平的miR-1254和miR-1306-5p与全因死亡率和HF住院的联合终点风险显著相关，每对数增加的风险比范围为1.11至1.21 （p值为0.004至0.009）。然而，将这些mirna添加到已建立的预测因子（年龄、性别、血红蛋白、肾功能和NT-proBNP）中并没有进一步增加c统计量，超过0.69（队列I）或0.70（队列II）。结论：我们对miRNA检测进行了严格的质量评估，并且能够在两个独立队列的HF患者中重复miR-1254和miR-1306-5p与死亡和HF住院风险的关联。然而，这两种循环mirna未能改善已建立的预测因子的预后。
Aims Small studies suggested circulating microRNAs (miRNAs) as biomarkers for heart failure (HF). However, standardized approaches and quality assessment for measuring circulating miRNAs are not uniformly established, and most studies have been small, so that results are inconsistent. We used a standardized data handling protocol, optimized for circulating miRNA qPCRs to remove noise and used it to assess which circulating miRNAs robustly add prognostic information in patients with HF.Methods and results We measured 12 miRNAs in two independent cohorts totalling 2203 subjects. Cohort I (Barcelona) comprised 834 chronic HF patients. Cohort II (Detroit) comprised 1369 chronic HF patients. Each sample was measured in duplicate, and normalized to a very abundant and stable miRNA (miR-486-5p). We used a multistep algorithm to distinguish false amplification signals and thus classify each miRNA measurement as 'valid', 'undetectable' or 'invalid'. Higher levels of miR-1254 and miR-1306-5p were significantly associated with risk of the combined endpoint of all-cause mortality and HF hospitalization in both cohorts, with hazard ratios ranging from 1.11 to 1.21 per log increase (P-values 0.004 to 0.009). However, adding these miRNAs to established predictors (age, sex, haemoglobin, renal function, and NT-proBNP) did not further augment the c-statistic beyond 0.69 (cohort I) or 0.70 (cohort II).Conclusion We used a stringent quality assessment for miRNA testing, and were able to replicate the association of miR-1254 and miR-1306-5p with risk of death and HF hospitalization in HF patients of two independent cohorts. However, these two circulating miRNAs failed to improve prognostication over established predictors.