氨基末端脑钠肽水平与老年血液透析合并心力衰竭死亡的相关性

孙 波，田红霞，李 晟，王月娥，荆 忱，王 军



氨基末端脑钠肽水平与老年血液透析合并心力衰竭死亡的相关性

孙 波1，田红霞1，李 晟1，王月娥1，荆 忱1，王 军2

目的 研究氨基末端脑钠肽(N terminal-pro brain nalriuretic peptide，NT-proBNP)水平与老年维持性血液透析并充血性心力衰竭死亡的相关性。方法 选择维持性血液透析并充血性心力衰竭入院患者52例，因心力衰竭死亡22例为死亡组，心力衰竭缓解30例为非死亡组，比较住院前、住院期间死亡组和非死亡组NT-proBNP水平，采用二分类Logistic回归分析影响死亡的相关因素，偏相关分析影响死亡组NT-proBNP水平的相关因素，受试者工作特征(ROC)曲线评价NT-proBNP水平对死亡的预测效能。结果 死亡组入院时NT-proBNP中位数为31 000 ng/L，与非死亡组入院时NT-proBNP中位数28 500 ng/L比较无统计学意义；死亡组住院期间NT-proBNP中位数为9200 ng/L，明显高于非死亡组NT-proBNP中位数4700 ng/L，差异有统计学意义(P<0.01)；二分类Logistic回归分析提示住院期间NT-proBNP水平为影响死亡的唯一相关因素(P<0.01)；左室EF值、透析间期体质量增加值、左室扩大为影响死亡组住院期间NT-proBNP水平相关因素(P<0.01)。死亡组住院期间NT-proBNP的AUC值为0.962，差异有统计学意义(P<0.05)；NT-proBNP>7650 ng/L作为界值(Cut off值)的敏感度为82.4%，特异度为84%；非死亡组住院期间NT-proBNP的AUC值为0.038，差异无统计学意义。结论 老年维持性血液透析并充血性心力衰竭住院期间高水平NT-proBNP与死亡具有相关性，可作为预测死亡的指标。

维持性血液透析；氨基末端脑钠肽；充血性心力衰竭；受试者工作特征；死亡

维持性血液透析(maintenance hemodialysis，MHD)患者心血管事件发生率高，合并充血性心力衰竭(CHF)比例大于非血液透析和非尿毒症者。NT-proBNP有判断心力衰竭程度和预后的价值[1-4]，但少见预测血液透析合并CHF死亡的报告，本研究回顾性分析了氨基末端脑钠肽水平与老年MHD并CHF死亡的相关性，旨在作为预测死亡的指标，为临床提供依据。

1 对象与方法

1.1 对象 选择2010-01至2015-12因终末期肾衰竭血液透析并CHF住院患者，根据是否死亡分为死亡组和非死亡组。入选标准:(1)血液透析1个月以上，每周血液透析>8 h;(2)年龄≥60岁，性别不限;(3)同时合并CHF，心功能Ⅲ级和Ⅳ级。排除标准：(1)合并肺心病、急性心肌梗死;(2)心功能Ⅰ级和Ⅱ级;(3)合并肿瘤者。用碳酸氢盐透析液透析,3次/周,采用醋酸空心纤维透析器(NIPRO Sureflus-150G透析器),膜面积1.5 m2,血流量180～220 ml/min,透析液流量500 ml/min。CHF按美国纽约心脏病协会(New Youk Heart Association,NYHA)心功能分级。

1.2 血浆NT-proBNP测定 于入院时、住院期间分别抽取血样，肝素锂抗凝。测定方法：采用丹麦AQT90 FLEX快速免疫分析仪检测,试剂由丹麦Radiometer Medical Aps提供,检测范围12～35 000 ng/L。1.3 左室扩大的评估 入院后行超声心动图检查，测量左心室射血分数(LVEF)、左室舒张末期后壁厚度(LVPWT)、左室舒张末期室间隔厚度(IVST)、左心室舒张末期内径(LVEDD)。LVEDD男≥5.5 cm，女≥5.0 cm诊断为左室扩大[5]。

1.4 实验室检查 治疗前采血测定血常规、钾钠氯、钙、磷、血糖、血肌酐(Scr)、尿素氮、全段甲状旁腺素(iPTH)、白蛋白。

1.5 统计学处理 采用SPSS 19.0软件进行分析。组间均数比较采用成组t检验；偏态分布变量用中位数(四分位数间距)表示，组间比较采用非参数检验，计数资料用χ2检验；P<0.05为差异有统计学意义。用二分类Logistic回归分析和偏相关分析死亡组与死亡相关因素以及住院期间NT-proBNP水平的影响因素，用ROC曲线评价NT-proBNP水平对预测死亡的诊断效能，用AUC及95%可信区间表示。

2 结 果

2.1 临床资料比较 两组年龄、性别比和心房颤动、冠心病，心功能分级例数及舒张压、血钾、白蛋白、血肌酐、尿素氮、iPTH、eGFR值比较均无统计学意义；左室扩大例数、收缩压、左室EF值、血红蛋白、透析间期体质量增加量比较差异有统计学意义(P<0.05,表1)。

表1 心力衰竭死亡组与非死亡组临床资料比较

项目死亡组(n=22)非死亡组(n=30)统计值P年龄(岁)74.10±6.4768.02±5.65t=1.271>0.05性别(男/女)15/719/11χ2=0.103>0.05左室扩大(有/无,例)16/610/20χ2=10.084<0.05心房颤动(有/无,例)6/164/26χ2=0.600>0.05冠心病(有/无,例)12/1013/17χ2=0.113>0.05心功能分级(Ⅲ级/Ⅳ级)5/1712/18χ2=1.018>0.05收缩压(mmHg)156.03(137.75～151.25)141.50(130.4-153.8)z=-1.862<0.05舒张压(mmHg)68.50(67.75～81.25)70.00(65.25-75.5)z=0.554>0.05左室EF值(%)42.59±4.8450.06±2.52t=-4.126<0.01血钾(mmol/L)4.21±0.674.06±0.53t=1.230>0.05血红蛋白(g/L)82.20(64.45～98.50)102.00(98.32-101.25)z=-2.836<0.05白蛋白(g/L)36.00(33.65～42.20)37.40(36.51～46.74)z=0.853>0.05血肌酐(μmol/L)870.50±148.40817.28±156.24t=0.623>0.05BUN(mmol/L)24.32±6.4626.40±5.08t=0.514>0.05iPTH(ng/L)312.30(158.47～1040.26)296.40(180.17～690.35)z=0.831>0.05残余尿量(ml/d)56.00(21～134)62.00(34～147)z=0.973>0.05eGFR[(ml/min·1.73m2)]8.40±1.208.82±1.13t=0.210>0.05透析间期体质量增加(Kg)4.52(4.0～4.5)3.20(3.4～3.9)z=-5.756<0.01

2.2 血浆NT-proBNP水平比较结果 入院时死亡组血浆NT-proBNP值为31.0×103ng/L，非死亡组血浆NT-proBNP值为28.5×103ng/L，两组比较差异无统计学意义；住院期间死亡组血浆NT-proBNP值为9.2×103ng/L，明显高于非死亡组血浆NT-proBNP值4.7×103ng/L，差异有统计学意义(P<0.01)。

2.3 死亡组相关因素的Logistic回归分析及偏相关分析结果 以死亡为因变量，选取表1中的左室扩大、收缩压、左室EF值、Hb、透析间期体质量增加以及入院时和住院期间NT-proBNP为自变量，用二分类Logistic相关分析结果提示死亡与住院期间NT-proBNP(Wald为7.163，Exp为1.124)相关(P<0.05)。偏相关分析提示住院期间NT-proBNP与透析间期体质量增加及左室EF值、左室扩大相关(P均<0.01)。

2.4 NT-proBNP对死亡组患者死亡判定的ROC曲线诊断效能 住院期间NT-proBNP判断老年血透并心力衰竭患者死亡的AUC值为0.962，大于0.5，差异有统计学意义(P<0.05)；NT-proBNP>7650 ng/L作为界值(Cut off值)的敏感度82.4%，特异度84%。

3 讨 论

MHD患者80%存在左心室肥厚、功能受损及缺血性心脏病等心血管并发症，其不良心血管事件发生率较正常人群高20倍，病死率约占MHD患者死因的50%以上[6]。NT-proBNP是心室肌细胞在容量和压力负荷增加时合成和分泌的多肽类神经激素，作为心血管疾病诊断、治疗和预后评价的重要生物学标志物已广泛用于心血管疾病的检查。

本研究发现，死亡组住院期间NT-proBNP水平明显高于非死亡组，而且死亡组存在更多的左室扩大、高收缩压、低的左室EF值、贫血纠正不佳、透析间期体质量增加等因素，提示这些指标是影响患者死亡的相关因素。进一步Logistic回归分析和偏相关分析显示住院期间高水平NT-proBNP和左室EF值、左室扩大是影响患者死亡的主要指标。有研究证明，NT-proBNP对心力衰竭诊断具有极高的敏感性和特异性，是1年死亡风险的强烈预测因素[7，8]。而且具有预测血液净化患者生存率的意义[9，10]。Paniagua等[11]对 753 例 MHD 患者随访16 个月，多变量分析显示NT-proBNP是独立于透析模式的全因病死率及心血管病死率的预测因子。本研究发现住院期间NT-proBNP水平主要受透析间期体质量增加影响。文献[12]报道导致NT-proBNP升高的各种心脏异常情况包括左心室收缩和舒张功能不全、心室大小和功能，其次与容量潴留有关。血液透析患者由于残余尿量减少，透析间期易出现容量负荷增加，超出心脏代偿范围后可伴有NT-proBNP升高，甚至出现心力衰竭。NT-proBNP水平除反映MHD患者心功能外，也是细胞外容量扩充的标志。即NT-proBNP与容量超负荷相关，可以用于评估患者的容量负荷[13]。这些结果说明血液透析患者在左室EF值下降基础上，透析间期体质量增加可增加心脏负荷，使心室肌张力增加，促使NT-proBNP产生增加。长期透析间期体质量增加也是诱发和加重心脏扩大、血压高和心力衰竭的风险因素。

本研究ROC曲线分析结果提示高水平NT-proBNP作为预测因CHF死亡具有较高敏感度和特异度。将治疗后的住院期间NT-proBNP水平持续大于7650 ng/L作为心血管事件及死亡预测指标有助于早期判断老年血液透析患者充血性心力衰竭死亡风险。以往一些研究发现经治疗后测定的出院前NT-proBNP水平比入院时NT-proBNP水平具有更高的预后评价能力[14，15]。高水平的 NT-proBNP 有较高的病死率[16]。这些研究虽然不是专门针对血液透析患者的研究，但证实持续高水平NT-proBNP是心血管意外及死亡的独立危险因素。目前在血液透析患者这个特殊人群还没有一个公认确定的监测心衰和判断预后的合适NT-proBNP水平范围。根据上述研究结果我们认为老年维持性血液透析并充血性心力衰竭住院期间高水平NT-proBNP与死亡具有相关性，可作为预测死亡的指标。

本研究由于病例数不多，还有待今后工作中继续观察，期待更多前瞻性大规模临床试验证实并确定NT-proBNP水平范围来指导临床工作。

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(2016-06-12收稿 2016-09-21修回)

(责任编辑 张 楠)

Relevance of NT-proBNP level to elderly hemodialysis patients with congestive heart failure

SUN Bo1,TIAN Hongxia1,LI Sheng1,WANG Yuee1,JING Chen1,and WANG Jun2.1.No.2 Department of Internal Medicine,2.School Office, Hospital Attached to Aeromedicine Institute of PLA, Beijing 100089,China

Objective To investigate the predictive value of the NT-proBNP level for elderly patients of maintenance hemodialysis and congestive heart failure. Methods 52 cases of maintenance hemodialysis combined with congestive heart failure were selected, 22 cases of congestive heart failure were selected as death group, and another 30 patients with congestive heart failure remission as non-death group. The NT-proBNP level before and during hospitalization was compared between the death group and non-death group. Binary logistic regression methods were used to analyze the correlation factors that affected death, especially the related factors that influenced NT-proBNP of death group. The diagnostic performance of NT-proBNP of patients was evaluated using the receiver-operating characteristic (ROC) curve to determine the prediction efficiency. Results The median value of NT-proBNP in death group before hospitalization was 31000ng/L, compared with 28 500 ng/L in non-death group. The difference was of no statistical significance(P>0.05). The median value of NT-proBNP in death group was 9200 ng/L before admission, significantly higher than 4700ng/L in non-death group. The difference was statistically significant (P<0.01). The left ventricular EF value , mass increase during dialysis and left ventricular enlargement were the main factors that influenced the NT-proBNP level of death group during hospitalization. The NT-proBNP AUC value of death group during hospitalization was 0.962, which was statistically significant(P<0.05). The sensitivity was 82.4% and the specificity was 84% when NT-proBNP>7650 ng/L served as the boundary value (cutoff value). NT-proBNP AUC value was 0.038 in non-death group during hospitalization, which was of no statistical significance. Conclusions The NT-proBNP level of elderly patients with maintenance hemodialysis combined with congestive heart failure can be used as a prediction index of death during hospitalization.

maintenance hemodialysis;n terminal-pro brain nalriuretic peptide;congestive heart failure;receiver operator characteristic;Death

孙 波，硕士研究生，副主任医师。

100089 北京，解放军航空医学研究所附属医院：1.内二科，2.院办

王 军，E-mail:wang_jun466@sina.com

R692.5