Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients
Circulating microRNAs as candidate markers to distinguish heart failure in breathless patients
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DOI：
10.1093/eurjhf/hft078
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发表时间：
2013-10-01
影响因子：
18.2
通讯作者：
Richards, A. Mark
中科院分区：
文献类型：
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作者：
Ellis, Katrina L.;Cameron, Vicky A.;Richards, A. Mark
自从它们在循环中被鉴定以来，microRNA作为心血管疾病的推定生物标志物受到了相当大的关注。我们研究了microRNA在区分心力衰竭（HF）和非HF相关呼吸困难患者，以及HF EF降低（HF-REF）和EF保持（HF-PEF）之间的诊断效用。对32名HF和15名COPD患者以及14名健康对照者的血浆进行了microRNA分析。在44例HF、32例COPD、59例其他呼吸困难和15例对照中选择了17种microRNA进行验证。HF病例平均分为HF-REF和HF-PEF。将诊断效用与NT-proBNP和高敏肌钙蛋白T（hs-肌钙蛋白T）进行比较。miR-103 [曲线下面积（AUC）0.642，P 0.007]，miR-142- 3 p（AUC 0.668，P 0.002），miR-199a-3p（AUC 0.668，P 0.002），miR-23a（AUC 0.637，P 0.010），miR-27 b（AUC 0.642，P 0.008），miR-324-5p在回归和受试者工作特征（ROC）分析中，miR-342- 3 p（AUC 0.644，P 0.007）与HF诊断相关。NT-proBNP（AUC 0.896，P 9.68 10（14））和hs-肌钙蛋白T（AUC 0.750，P 2.50 10（6））显示出更高的灵敏度和特异性。然而，将显著相关的microRNA与NT-proBNP组合使NT-proBNP的AUC提高了4.6（P 0.013）。HF与对照、COPD和其他呼吸困难患者之间有4种microRNA（miR-103、miR-142- 3 p、miR-30 b和miR-342- 3 p）的差异表达（P 0.0020.030）。在筛选中区分HF-REF和HF-PEF的8种microRNA（P 0.017 0.049）在验证中没有重复。4种microRNA区分HF和COPD加重、其他呼吸困难原因和对照。在回归和ROC分析中，7个与HF诊断相关。虽然单独的NT-proBNP在预测HF方面远远优于上级，但将microRNA水平与NT-proBNP结合可能会增加诊断价值。
Since their identification in the circulation, microRNAs have received considerable interest as putative biomarkers of cardiovascular disease. We have investigated the diagnostic utility of microRNAs in differentiating between patients with heart failure (HF) and non-HF-related breathlessness, and between HF with reduced (HF-REF) and preserved (HF-PEF) EF.MicroRNA profiling was performed on plasma from 32 HF and 15 COPD patients, as well as 14 healthy controls. Seventeen microRNAs were selected for validation in 44 HF, 32 COPD, 59 other breathless, and 15 controls. Cases of HF were split evenly between HF-REF and HF-PEF. Diagnostic utility was compared with NT-proBNP and high sensitivity troponin T (hs-troponin T). MiR-103 [area under the curve (AUC) 0.642, P 0.007], miR-142-3p (AUC 0.668, P 0.002), miR-199a-3p (AUC 0.668, P 0.002), miR-23a (AUC 0.637, P 0.010), miR-27b (AUC 0.642, P 0.008), miR-324-5p (AUC 0.621, P 0.023), and miR-342-3p (AUC 0.644, P 0.007) were associated with HF diagnosis in regression and receiver operating characteristic (ROC) analyses. Individually, NT-proBNP (AUC 0.896, P 9.68 10(14)) and hs-troponin T (AUC 0.750, P 2.50 10(6)) exhibited greater sensitivity and specificity. However, combining significantly associated microRNAs with NT-proBNP improved the AUC of NT-proBNP by 4.6 (P 0.013). Four microRNAs, miR-103, miR-142-3p, miR-30b, and miR-342-3p, were differentially expressed between HF and controls, COPD, and other breathless patients (P 0.0020.030). Eight microRNAs that distinguished between HF-REF and HF-PEF in screening (P 0.0170.049) were not replicated in the validation.Four microRNAs distinguished between HF and exacerbation of COPD, other causes of dyspnoea, and controls. Seven were associated with HF diagnosis in regression and ROC analysis. Although individually NT-proBNP was far superior in predicting HF, combining microRNA levels with NT-proBNP may add diagnostic value.