血浆microRNA-21水平与左室射血分数保留的心力衰竭相关性肺高压的关系

Association between plasma level of microRNA-21 and pulmonary hypertension in heart failure patients with preserved ejection fraction

目的:探讨血浆微小RNA-21(miR-21)水平与左室射血分数保留的心力衰竭(HFpEF)相关性肺高压(PH-HFpEF)的关系。方法:选择2014年1月～2017年2月在江西省人民医院心内科就诊的HFpEF患者102例,通过三尖瓣反流压差法估测肺动脉收缩压(pulmonary artery systolic pressure,PASP),并按PASP分为PH-HFpEF组(n=36,PASP≥50 mmHg)和HFpEF组(n=40,PASP <50 mmHg),另选年龄和性别相应的同期健康体检者作为对照组(n=36),比较各组患者的临床资料,血浆miR-21水平与临床资料的相关性用Spearman相关分析,血浆miR-21水平预测PH-HFpEF准确性用受试者工作特征(ROC)曲线分析。多因素logistic回归分析与PH-HFpEF相关的危险因素。结果:PH-HFpEF组患者年龄、血浆内皮素1(ET-1)、血浆白细胞介素6(IL-6)、脑钠尿肽(BNP)和左房直径(LAD)均高于HFpEF组(P <0. 05)。PH-HFpEF组血浆miR-21表达明显高于HFpEF组及健康对照组(P <0. 05)。Spearman相关分析显示,血浆miR-21与PASP (r=0. 267,P=0. 000)、血浆IL-6 (r=0. 302,P=0. 013)和左心室重量指数(LVMI)(r=0. 515,P=0. 036)相关;血浆IL-6与ET-1正相关(r=0. 622,P=0. 002);PASP分别与血浆IL-6 (r=0. 36,P=0. 023)、ET-1 (r=0. 76,P=0. 004)、BNP (r=0. 43,P=0. 031)及LAD (r=0. 39,P=0. 044)正相关。血浆miR-21诊断PH-HFpEF的ROC曲线分析显示,曲线下面积为0. 8。多因素logistic回归分析显示,血浆miR-21相对表达水平、LAD、BNP与HFpEF患者肺高压相关。结论:血浆miR-21水平与PHHFpEF呈正相关,是HFpEF患者出现肺高压的独立预测因素。血浆miR-21可能是PH-HFpEF的标志物。

AIM:To investigate the correlation between microRNA-21(miR-21)and pulmonary hypertension(PH)in the patients with heart failure with preserved ejection fraction(HFpEF).METHODS:From January 2014 to February 2016,102 HFpEF patients presenting to Jiangxi Provincial People’s Hospital were enrolled in this study.The patients were divided into PH-HFPEF group(n=36,PASP≥50 mmHg)and HFpEF group(n=40,PASP<50 mmHg).Another 36 age-and sex-matched subjects served as healthy controls.The plasma level of miR-21 and its correlations with clinic data were examined,and multivariate logistic regression analysis was performed to identify the independent predictors of PH-HFpEF.Receiver operating characteristic(ROC)curve was analyzed,and the area under the curve(AUC)was calculated.The sensitivity and specificity for PH-HFPEF diagnosis were also determined.RESULTS:Age,plasma endothelin-1(ET-1),interleukin-6(IL-6),brain natriuretic peptide(BNP)and left atrial diameter(LAD)were significantly higher in PH-HFPEF group than those in HFPEF group(P<0.05).The level of miR-21 was significantly increased in PH-HFPEF group compared with HFpEF group and healthy control group.In addition,the miR-21 level was correlated with PASP(r=0.267,P=0.000),plasma IL-6(r=0.302,P=0.013)and left ventricular mass index(LVMI)(r=0.515,P=0.036).Plasma IL-6 was positively correlated with plasma ET-1(r=0.622,P=0.002).PASP was positively correlated with plasma IL-6(r=0.36,P=0.023),ET-1(r=0.76,P=0.004),BNP(r=0.43,P=0.031),and LAD(r=0.39,P=0.044).ROC curve showed that the AUC of miR-21 was 0.80.Multivariate logistic regression analysis showed that miR-21,LAD and BNP were the independent predictors of PH-HFpEF.CONCLUSION:Increased plasma miR-21 level is positively correlated to PH-HFpEF,and is an independent predictor of PH-HFpEF,suggesting that plasma miR-21 might be a useful new biomarker for predicting PH in HFpEF patients.