Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction

• Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients. 目的： 探讨入院基线N末端B型利钠肽原（NT-proBNP）对射血分数保留的心力衰竭（HFpEF）患者全因死亡的预测价值。 方法： 入选中国住院患者心力衰竭注册研究（CN-HF）中符合HFpEF诊断标准的患者，根据随访期间是否死亡分为死亡组和存活组。从CN-HF中获得研究对象的人口学信息、入院时体格检查信息、入院首次超声心动图检查结果、实验室检查结果、合并症情况、用药情况和临床结局等资料。通过单因素Cox回归模型对可能预测预后的变量进行筛选，将单因素分析中与全因死亡有统计学意义的协变量纳入多因素Cox回归模型，进而分析基线NT-proBNP对全因死亡的预测价值。采用Spearman相关分析分析NT-proBNP与估算的肾小球滤过率（eGFR）的关系，并进一步探讨肾功能不全与NT-proBNP预测全因死亡的交互作用。鉴于NT-proBNP不服从二元正态分布，本研究中NT-proBNP作连续变量分析时均取自然对数（LnNT-proBNP）。 结果： 共1 846例患者纳入本研究，平均年龄71.5岁，男性1 017例（55.1%），NT-proBNP中位数860 ng/L，eGFR中位数73.9 ml·min-1·1.73m-2。本研究中位随访时间34（24~42）个月，随访期间全因死亡213例（11.5%）被纳入死亡组，存活1 633例（88.5%）被纳入存活组。与存活组比较，死亡组患者年龄较大，纽约心脏协会（NYHA）心功能Ⅲ~Ⅳ级者比例较高，住院时间较长，血钾、NT-proBNP较高，合并糖尿病、心律失常、心房颤动者较多，服用血管紧张Ⅱ受体阻滞剂（ARB）、盐皮质激素受体拮抗剂（MRA）、利尿剂和地高辛者较多（P均<0.05）。与存活组比较，死亡组患者体重指数（BMI）、舒张压、左心室射血分数（LVEF）较低，血红蛋白、血清总胆固醇（TC）、血清甘油三酯（TG）、eGFR较低，服用血管紧张素转化酶抑制剂（ACEI）、他汀类药物和阿司匹林者较少（P均<0.05）。单因素Cox回归分析结果显示NT-proBNP是HFpEF患者全因死亡的预测因素（HR=2.522，95%CI 2.040~3.119，P<0.001）。多因素Cox回归分析结果显示，校正了年龄、BMI、舒张压、LVEF、血红蛋白、血钾、血钠、TC、高密度脂蛋白胆固醇、TG、eGFR、心房颤动以及ACEI/ARB、MRA、利尿剂、地高辛使用情况后，NT-proBNP仍是HFpEF患者全因死亡的独立预测因素（HR=1.230，95%CI 1.049~1.442，P=0.011）。Spearman相关分析结果显示，LnNT-proBNP与eGFR呈负相关（r=-0.361，P<0.001）。而校正了混杂因素后，多因素Cox回归分析结果显示肾功能不全与NT-proBNP预测HFpEF患者全因死亡无交互作用（P>0.05）。 结论： 入院基线NT-proBNP是HFpEF患者全因死亡的独立预测因素。.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Keyword

Heart failure

N-terminal B-type natriuretic peptide

Prognosis

biological marker

brain natriuretic peptide

peptide fragment

aged

China

female

heart stroke volume

human

male

Biomarkers

Humans

Natriuretic Peptide

Brain

Peptide Fragments

Stroke Volume

Publication and Content Type

ref (subject category)

art (subject category)