NTproBNP在老年人慢性心力衰竭评估中的临床意义

　　作者：黄春，吴文伟，徐春平，杨文彦，董开武，陈晓春 作者单位：福建医科大学 附属协和医院干部病房，福建省老年医学研究所，福州 350001

　　【摘要】 目的 观察≥70岁老年患者心衰不同阶段、心功能分级和左室射血分数(LVEF)对血清氨基末端钠尿肽前体(NTproBNP)水平的影响。 方法 入选老年住院患者121例。入院即刻评估慢性心衰所处阶段、NYHA心功能分级，超声心动图评估LVEF，电化学发光免疫法测定血清NTproBNP水平。 结果 (1)慢性心衰A,B,C,D各阶段血清NTproBNP的中位数(Median)分别为61.5,95.0,1 102.0和9 995.5 ng/L。非参数检验显示各组间有显著差异(P=0.000)。各组间年龄、性别构成无显著差别。左室舒张末期内径(LVEDD)/LVEF随着心衰的发展而增大/降低。(2)血清NTproBNP水平随NYHA心功能分级恶化而增加(P=0.000)。各组间年龄、性别构成无显著差别。(3)LVEF<50%组血清NTproBNP水平显著高于LVEF≥50%组(P=0.000)。 结论 ≥70岁老年患者血清NTproBNP水平与传统的心衰临床评估手段呈现一致的变化，较准确反映慢性心衰的发展进程并随着心衰症状的加重而增加。

　　【关键词】 利钠肽，脑;心力衰竭，充血性;慢性病

　　Clinical Value of NTproBNP in Diagnosis of Chronic Heart Failure in Elderly Patients

　　HUANG Chun,WU Wenwei,XU Chunping,YANG Wenyan,DONG Kaiwu,CHEN Xiaochun

　　Fujian Institute of Geriatrics, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, 350001, China

　　ABSTRACT: Objective To investigate the serum concentration of Namino terminal probrain natriuretic peptide (NTproBNP) in elderly patients (aged 70 years and older) based on the chronic heart failure (CHF) stages, NYHA function classification, and left ventricular ejection fraction (LVEF). Methods CHF stages and NYHA function classification were determined for 121 patients on admission. LVEF and LVEDD were assessed by echocardiography and NTproBNP was assayed by Roche Diagnostics. Results (1) The median NTproBNP level increased with the progress of CHF stages, respectively, stage A 61.5 ng/L, stage B 95.0 ng/L, stage C 1 102.0 ng/L, and stage D 9 995.5 ng/L, P=0.000 by nonparametric test. The constitution of age and sex of patients was similar among the groups. With the progress of CHF stages, LVEDD increased and LVEF decreased. (2) NTproBNP concentration was directly paralleled to the severity of HF symptoms based on NYHA function classification, P=0.000. The constitution of age and sex of patients was similar among the groups. LVEF was negatively associated with NYHA function classification. (3) Based on LVEF, NTproBNP concentration was higher in patients with LVEF<50% than that in those with LVEF≥50%, P=0.000. LVEF was negatively associated with NTproBNP level. Conclusion For patients aged 70 years and older, serum NTproBNP concentration, consistent with the traditional clinical parameters in evaluating heart failure, is an effective biomarker predictor for monitoring the progress and severity of CHF.To investigate the serum concentration of Namino terminal probrain natriuretic peptide (NTproBNP) in elderly patients (aged 70 years and older) based on the chronic heart failure (CHF) stages, NYHA function classification, and left ventricular ejection fraction (LVEF) . Methods CHF stages and NYHA function classification were determined for 121 patients on admission. LVEF and LVEDD were assessed by echocardiography and NTproBNP was assayed by Roche Diagnostics kit. Results (1) The median NTproBNP level increased with the progress of CHF stages, respectively, stage A[61.5 ng/L, range(22 to 239) ng/L], stage B[95.0 ng/L, range(15 to 458) ng/L], stage C[1 102.0 ng/L, range(112 to 7108) ng/L], and stage D[9 995.5 ng/L, range (566 to 35000) ng/L], P=0.000 by nonparametric test. The constitution of age and sex of patients was similar among the groups. With the progress of CHF stages, LVEDD increased and LVEF decreased. (2) NTproBNP concentration was directly paralleled to the severity of HF symptoms based on NYHA function classification, P=0.000. The constitution of age and sex of patients was similar among the groups. LVEF was negatively associated with NYHA function classification. (3) Based on LVEF, NTproBNP concentration was higher in patients with LVEF<50% than that in those with LVEF≥50%, P=0.000. LVEF was negatively associated with NTproBNP level. Conclusion For patients aged 70 years and older, serum NTproBNP concentration, consistent with the traditional clinical parameters in evaluating heart failure, is an effective biomarker predictor for monitoring the progress and severity of CHF.

　　KEY WORDS: natriuretic peptide, brain ; heart failure, congestive ; chronic disease

　　心力衰竭是心血管事件链的最后一个环节，是导致心血管病死亡的首要原因。既往对心衰的诊断主要依据症状体征和超声心动图、X光胸片等影像学检查，缺乏相应的实验室指标。老年患者由于各脏器生理机能的衰退，往往多种疾病并存，疾病间会彼此相互影响和掩盖，部分患者因认知功能障碍不能表达早期的症状和搬动困难，导致误诊或不能及时诊断而使病情重症化。

　　近年来，B型钠尿肽(brain natriuretic peptide，BNP)检测作为一种方便、有效的手段广泛地应用于急性呼吸困难的心源性/肺源性鉴别诊断，而氨基末端钠尿肽前体(Namino terminal probrain natriuretic peptide，NTproBNP)因其半衰期更长、更稳定，更适用于临床检查[1]。高龄、肾功能不全和急性脓毒症等可均影响BNP和NTproBNP水平，并有可能削弱其诊断价值。笔者观察老年患者血清NTproBNP在慢性心衰不同阶段、纽约心脏协会(New York Heart Association，NYHA)心功能分级、不同左室射血分数(left ventricular ejection fraction，LVEF)中的变化，了解其对老年患者心衰诊断评估和临床严重程度的预测价值。

　　1 对象与方法

　　1.1 对象

　　收集笔者医院2007年6月-2008年7月期间住院治疗的老年患者121例，入选标准：符合“2007年中国慢性心力衰竭诊断治疗指南”的心衰各阶段患者[2];排除标准：急性心肌梗塞、慢性阻塞性肺病、脓毒症、慢性肾功能不全和痴呆患者。其中男性88例，女性33例;年龄(78.3±6.0)岁(70～95岁)。疾病构成：冠心病98例(81.0%)，高血压病93例(76.9%)，糖尿病44例(36.4%)，代谢综合征15例(12.4%)，扩张型心肌病3例(2.5%)，心动过速心肌病1例(0.8%)，心脏毒性药物史7例(5.8%);慢性心衰分级：A级14例(11.6%)，B级39例(32.2%)，C级54例(44.6%)，D级14例(11.6%);NYHA心功能分级：Ⅰ级53例(43.8%)，Ⅱ级26例(21.5)，Ⅲ级22例(18.2%)，Ⅳ级20例(16.5%)。

　　1.2 研究方法及观察指标

　　入院即刻进行心衰各阶段(前心衰阶段A、前临床心衰阶段B、临床心衰阶段C、难治性心衰阶段D)的评估和NYHA心功能分级评估。采用罗氏公司的电化学发光双抗体夹心法测定血清NTproBNP水平(每一批次样品的检测均用罗氏公司提供的质控品进行监测)。超声心动图测定左室舒张末期内径(left ventricular end diastolic diameter,LVEDD)和LVEF。

　　1.3 统计学处理

　　计量资料以x±s表示。采用SPSS 14.0统计软件包处理，符合正态分布的计量资料多个均数间比较采用单因素方差分析，不符合正态分布的计量资料采用非参数检验，计数资料采用Fisher’s精确检验，NTproBNP与其他指标的相关性采用Spearman's rho分析。P<0.05为差别有统计学意义。

　　2 结 果

　　2.1 慢性心衰不同阶段血清 NTProBNP水平和超声心动图心功能指标的变化

　　慢性心衰A,B,C,D各阶段 NTproBNP的中位数分别为61.5，95.0，1 102.0和9 995.5 ng/L，非参数检验显示各组间有显著差异(P=0.000)。各组间年龄、性别构成无显著差别，年龄和性别与NTproBNP的水平无显著相关性;LVEDD/LVEF随着心衰的发展而增大/降低，多组间均数比较年龄无显著差别(P=0.126，单因素方差分析)，性别无显著差别(P=0.156，Fisher’s精确检验)，LVEDD和LVEF有显著差异(P=0.000，单因素方差分析)，NTproBNP有显著差异(P=0.000，非参数检验);各组间两两比较显示：阶段A和阶段B之间无差异，其余各组间两两比较有显著差异(表1)。表1 慢性心衰不同阶段超声心动图心功能指标及NTproBNP水平变化(略)

　　2.2 NYHA心功能分级对血清NTproBNP水平和超声心动图心功能指标的影响

　　随着NYHA心功能分级的恶化，NTproBNP水平逐渐升高(P=0.000);LVEF随心功能恶化而降低(P=0.000);LVEDD则随心功能恶化而增大(P=0.000);多组间比较：年龄无显著差别(P=0.566，单因素方差分析)，性别无显著差别(P=0.165，Fisher’s精确检验)，LVEDD和LVEF有显著差异(P=0.000，单因素方差分析)，NTproBNP有显著差异(P=0.000，非参数检验，表2)。表2 NYHA心功能分级对NTproBNP水平和超声心动图心功能指标的影响(略)

　　2.3 不同LVEF患者NTproBNP水平的变化

　　将慢性心衰患者按照LVEF高低分成两组，与LEVF正常组(LVEF≥50%)患者相比较，LVEF<50%者NTproBNP水平显著升高(P=0.000)，LVEDD显著增加(P=0.000)，LVEF与NTproBNP呈负相关(r=-0.315，P=0.000);LVEDD与NTproBNP呈正相关(r=0.29，P=0.000);两组间比较：年龄无显著差别(P=0.195，单因素方差分析)，性别无显著差别(P=0.176，卡方检验)，LVEDD有显著差异(P=0.000，单因素方差分析)，NTproBNP有显著差异(P=0.000，非参数检验，表3).表3 不同LVEF患者NTproBNP水平变化(略)

　　3 讨 论

　　根据心衰发生发展的过程，将心衰分成A、B、C、D四个阶段，有助于提供从“防”到“治”的全面干预[3]。本研究根据2007年中国CHF指南，对入选患者进行慢性心衰的阶段评估，发现≥70岁患者至少有1项或1项以上心衰危险因素，常见的心衰危险因素和病因有高血压病、冠心病、糖尿病和代谢综合症，其他疾病包括心动过速性心肌病、扩张型心肌病和心脏毒性药物史，未发现心肌炎和风湿性心脏病患者，可能与笔者科室收住患者高龄、多数为保健对象、医疗条件较好有关。

　　本结果表明，在心衰发生发展过程中，A或B阶段NTproBNP水平较低，C和D阶段NTproBNP水平显著升高，且阶段D高于阶段C，提示NTproBNP随着心衰的发展进程而逐渐升高，与心衰症状的发生密切相关，并随心衰症状的加重(NYHA心功能分级的恶化)而增加。按LVEF分组，LVEF<50%的患者NTproBNP中位数显著高于LVEF≥50%组，与PRIDE超声心动图的亚组研究的趋势一致[4]。由此可见，对于≥70岁的老年患者，心脏生物学标志物NTproBNP水平与传统的心衰临床评估手段呈现一致的变化，能够较准确地反映慢性心衰的发展进程和严重程度，与国内外的研究结果相一致[56]。在心衰发展的不同阶段、NYHA心功能不同级别中，本研究入选患者年龄和性别组成无差别，可排除各组间NTproBNP水平变化受年龄和性别因素的影响。

　　综上所述，老年人是心衰的高发人群，并存疾病多，症状不典型且互相掩盖，检测NTproBNP能快速、简便地反映心室壁张力，对老年患者早期识别心衰和评估心衰严重程度具有重要的参考价值，可以作为老年人心衰诊断和评估的常规指标。但是，70岁以上老年患者若合并肾功能不全、心房颤动和脓毒症等其他病理状况，NTproBNP对心衰的诊断阈值，尚有待前瞻性、随机对照临床研究的结果进行界定。

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