老年慢性心力衰竭患者血清microRNA-208a、CASP3与心室重构和预后的关系

Association of serum microRNA-208a and CASP3 levels with ventricular remodeling and prognosis in elderly patients with chronic heart failure

摘要:

目的 探讨老年慢性心力衰竭（CHF）患者血清microRNA-208a（miR-208a）、含半胱氨酸的天冬氨酸蛋白水解酶3（CASP3）与心室重构和预后的关系。方法 选取2019年1月—2021年9月新余市中医院收治的155例老年CHF患者为CHF组，另选取同期该院体检健康者57例为对照组，CHF组患者根据预后情况分为预后不良组（58例）和预后良好组（97例）。实时荧光定量聚合酶链反应（qRT-PCR）检测miR-208a mRNA相对表达量；酶联免疫吸附试验（ELISA）检测CASP3、B型脑利钠肽（BNP）水平；采用Pearson/Spearman相关系数分析老年CHF患者血清miR-208a、CASP3与BNP、右心室内径（RVD）、左心室舒张末期内径（LVEDD）、左心室短轴缩短率（LVFS）、左室射血分数（LVEF）、左心室质量指数（LVMI）的相关性；多因素Logistic回归分析老年CHF患者预后不良的影响因素；绘制受试者工作特征（ROC）曲线分析血清miR-208a、CASP3对老年CHF患者预后不良的预测价值。结果 CHF组血清miR-208a、CASP3、BNP水平，LVMI高于对照组，RVD、LVEDD大于对照组，LVFS、LVEF低于对照组（P <0.05）。Pearson/Spearman相关性分析结果显示，老年CHF患者血清miR-208a、CASP3与BNP、RVD、LVEDD、LVMI呈正相关（r /r_s =0.577、0.627、0.535、0.619和0.619、0.721、0.601、0.631，均P <0.05），与LVFS、LVEF呈负相关（r /r_s =-0.555、-0.568和-0.655、-0.700，均P <0.05），血清miR-208a与CASP3呈正相关（r_s =0.638，P <0.05）。多因素Logistic回归分析结果显示，NYHA ≥Ⅲ级［O^R=3.383（95％ CI：1.358，8.423）］、BNP［O^R=1.006（95% CI：1.002，1.009）］、LVMI［O^R=1.114（95% CI：1.005，1.233）］、miR-208a［O^R=1.203（95% CI：1.096，1.321）］、CASP3［O^R=1.196（95% CI：1.088，1.315）］为老年CHF患者预后不良的独立危险因素（P <0.05），LVEF［O^R=0.867（95％ CI：0.753，0.998）］为独立保护因素（P <0.05）。ROC曲线分析结果显示，血清miR-208a、CASP3单独及联合预测老年CHF患者预后不良的ROC曲线下面积（AUC）分别为0.785、0.783和0.867。结论 血清miR-208a、CASP3与老年CHF患者心室重构和预后密切相关，可能成为老年CHF患者预后不良的辅助预测指标。

Abstract:

Objective To investigate the relationship of serum microRNA-208a (miR-208a) and cysteinyl aspartate specific proteinase 3 (CASP3) levels with ventricular remodeling and prognosis in elderly patients with chronic heart failure (CHF).Methods A total of 155 elderly patients with CHF admitted from January 2019 to September 2021 in Xinyu Traditional Chinese Medicine Hospital (CHF group) were selected and divided into a poor prognosis subgroup (n = 58) and a good prognosis subgroup (n = 97) according to their prognosis, and another 57 healthy patients (control group) were selected from the hospital physical examination during the same period. The miR-208a level was measured by qPCR and the CASP3 level was measured by ELISA. The correlation between serum miR-208a and CASP3 levels and B-type brain natriuretic peptide (BNP), right ventricular diameter (RVD), left ventricular end diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS), left ventricular ejection fraction (LVEF), and left ventricular mass index (LVMI) in elderly patients with CHF was analyzed using Pearson/Spearman correlation coefficients, multi-factor logistic regression was used to analyze the factors influencing poor prognosis in elderly CHF patients, and ROC curves were used to analyze the predictive value of serum miR-208a and CASP3 levels on poor prognosis in elderly CHF patients.Results Serum levels of miR-208a, CASP3, and BNP, and RVD, LVEDD and LVMI were higher in the CHF group than in the control group, and LVFS and LVEF were lower than in the control group (P < 0.05). Pearson/Spearman correlation coefficients showed that serum miR-208a and CASP3 levels in elderly CHF patients were positively correlated with BNP, RVD, LVEDD, and LVMI (r / r_s = 0.577, 0.627, 0.535, 0.619, 0.619, 0.721, 0.601 and 0.631, all P < 0.05) and negatively correlated with LVFS and LVEF (r / r_s = -0.555, -0.568, -0.655 and -0.700, all P < 0.05); serum miR-208a was positively correlated with CASP3 levels (r_s = 0.638, P < 0.05). Multifactorial logistic regression analysis showed that NYHA classification ≥ grade Ⅲ [O^R = 3.383 (95% CI: 1.358 , 8.423) ] and BNP [O^R = 1.006 (95% CI: 1.002, 1.009) ], LVMI [O^R = 1.114 (95% CI: 1.005, 1.233) ], miR-208a [O^R = 1.203 (95% CI: 1.096, 1.321) ], and CASP3 [O^R = 1.196 (95% CI: 1.088, 1.315) ] were independent risk factors for poor prognosis in elderly CHF patients, and elevated LVEF [O^R = 0.867 (95% CI: 0.753, 0.998) ] was an independent protective factor (all P < 0.05). ROC curve analysis showed that the area under the curve for serum miR-208a and CASP3 levels alone and in combination to predict poor prognosis in elderly CHF patients was 0.785, 0.783 and 0.867, respectively.Conclusion Elevated levels of serum miR-208a and CASP3 are closely associated with ventricular remodeling and poor prognosis in elderly CHF patients, and may be an auxiliary predictor of poor prognosis in elderly CHF patients.