N末端B型钠尿肽原和大内皮素-1对严重心力衰竭患者的预后作用及其与心血管病关系的研究

Prognostic value of NT-proBNP and big ET-1 in severe heart failure:significance of NT-proBNP and big ET-1 in cardiovascular diseases combining with severe heart failure

目的探讨两检测指标血浆 N 末端 B 型钠尿肽原(NT-proBNP)和大内皮素-1(bigET-1)之间,两指标与心力衰竭(心衰)伴心房颤动(Af)、心衰伴肺动脉高压(PAH)等心血管病的关系,以及两指标对严重心衰患者半年期预后的预测价值。方法阜外医院严重心衰患者132人,测定他们入院时的血浆 LgNT-proBNP 和 big ET-1浓度(酶联免疫法)以及纽约心脏病协会心功能分级(NYHA分级)、左室射血分数(LVEF)等指标。随访观察患者出院后半年内心血管事件的再发生。结果严重心衰患者132人(NYHAⅢ-Ⅳ级,年龄24～80岁,男83人,女49人,LVEF 13%～66%),其血浆 LgNT-proBNP 与 big ET-1呈正相关(r=0.414,P=0.000)。有、无 Af 的两组间 big ET-1水平比较差异有统计学意义(P=0.022);有、无 PAH 的两组间 LgNT-proBNP 和 big ET-1浓度差异均有统计学意义(P=0.019,P=0.000)。以 big ET-1诊断严重心衰患者伴 PAH 的 ROC 曲线下面积为0.74(95%CI:0.65～0.83,P=0.000),以4.09 fmol/ml 为 big ET-1诊断心衰伴 PAH 的 cutoff 值时,灵敏度为71.4%,特异度67.8%。经过6个月的随访,132例严重心衰患者中,有20例发生心源性死亡(15.2%),有25例因心脏原因再住院(18.9%)。Cox 比例风险模型分析显示,包括了年龄、性别、NYHA 分级、LVEF、LgNT-proBNP、big ET-1等指标后,只有 NT-proBNP 是独立的心脏事件再发生的预后因素,RR 为5.30(95%CI:2.07～13.55,P=0.001)。Logistic 回归显示也只有 NT-proBNP 是独立的心源性死亡发生的危险因素,OR 为13.67(95%CI:2.59～72.25,P=0.002)。big ET-1、LVEF、NYHA分级等指标对严重心衰患者心血管事件再发生没有预后价值。结论 NT-proBNP 与 big ET-1间可能存在相互作用;严重心衰伴 Af 的患者可能有内皮细胞损伤和功能异常;big ET-1可辅助诊断严重心衰患者伴发 PAH;NT-proBNP 可用于严重心衰患者半年期预后的评估,而 big ET-1没有此预测价值。

Objective To investigate the prognostic ability of NT-proBNP （N-terminal B-type natriuretic peptide） and big ET-1 （big endothelin-1 ） in patients with severe heart failure （HF）, and the correlation of NT-proBNP and big ET-1 with atrial fibrillation （M） and pulmonary artery hypertension （PAH） in severe HF patients. Methods Plasma concentrations of NT-proBNP and big ET-1 in 132 consecutive patients with severe HF were measured on admission. The left ventricular ejection fractions （LVEF） of the patients were also measured. Results The 132 patients consisted of 83 males and 49 females aged 24-80 years. All the patients showed severe HF （ NYHA class Ⅲ to Ⅳ, LVEF 13% -66% ） . The LgNT-proBNP were positively correlated with big ET-1 （ r = 0. 414, P 〈 0. 001 ） in the patients. Significant differences were observed in plasma big ET-1 concentrations between HF patient groups with and without M and between groups with and without PAH （P 〈0. 05 and P 〈0. 001, respectively）. Plasma big ET-1 was moderately accurate in discriminating HF patients with or without PAH. The area under ROC curve was 0.74 （95% CI： 0. 65-0. 83 ,P 〈0. 001 ） with 71.4 % sensitivity and 67.8% specificity at a cutoff of 4. 09 fmol/ ml. during a follow-up of 6 months, there were 20 deaths and 25 readmissions in 132 HF patients. On a Cox proportional hazards analysis, NT-proBNP was an independent predictor of cardiac events, with a RR of 5.30 （95% CI 2.07-13.55 ,P =0. 001 ）, and the only independent predictor of death with an OR of 13. 67 （95% CI 2. 59-72. 25 ,P =0. 002）. Big ET-1, LVEF and NYHA were not independent predictors of cardiac events. Conclusions There is a possible interaction between NT-proBNP and big ET-1. Endothelia damage may exist in HF patient with Af. The plasma big ET-1 level may be useful as an aid in the diagnosis of HF patients with PAH. NT-proBNP, but not big ET-1 is independently predictive of cardiac events in severe HF. Measurement of NT-proBNP in severe HF patients is beneficial to identify patients at higher short-term risk of cardiac events.