血浆NT-proBNP、血清ST2与急性失代偿性心力衰竭预后评估

贺明轶,秦俭(首都医科大学宣武医院急诊科,北京 100053)

·论 著·

血浆NT-proBNP、血清ST2与急性失代偿性心力衰竭预后评估

贺明轶,秦俭*
(首都医科大学宣武医院急诊科,北京 100053)

目的 观察急性失代偿性心力衰竭(ADHF)患者血浆NT-proBNP和血清ST2水平变化,探讨其与ADHF患者预后的关系。方法 选取2011年7月～2012年4月期间急诊科就诊的ADHF患者75例(心衰组), 根据预后分为事件组30例及非事件组45例；选取同期健康体检者42例为对照组。检测并比较血浆NT-proBNP、血清ST2、CK-MB、cTnI及超声心动图等指标。 结果 ADHF患者NT-proBNP、ST2均高于对照组(P<0.01)；事件组NT-proBNP、ST2和cTnI均高于非事件组(P<0.01或P<0.05)；NT-proBNP、ST2和cTnI与预后呈正相关。Logistic回归分析显示,NT-proBNP [B=1.61,P<0.01,OR=4.43,95%CI=(2.20～10.98)]和ST2[B=1.7,P<0.01,OR=2.03,95%CI(1.47～4.16)]是不良预后的独立预测因子。结论 NT-proBNP、ST2水平升高是ADHF患者不良预后的危险因素。

急性失代偿性心力衰竭；NT-proBNP；ST2；预后

急性失代偿性心力衰竭(acute decompensated heart failure, ADHF)临床上以突发严重的呼吸困难为首要症状,可表现为急性肺水肿或心源性休克,严重时甚至危及生命。ST2蛋白是白介素-1受体家族成员之一, 其基因的发现可追溯到 1989 年小鼠成纤维细胞的研究[1]。ST2 基因主要编码两个差异性剪切产物,即血清可溶性 ST2 蛋白(sST2) 和跨膜性 ST2 蛋白(ST2L)。ST2是生物机械应力产生的一种心肌蛋白,可由心肌成纤维细胞及心肌细胞表达[2]。近年来国外多个研究[3-5]均肯定了ST2在心功能不全诊断、严重程度及预后评价方面的价值。NT-proBNP(N-terminal-probrain natriuretic peptide, NT-proBNP)是由前BNP(pro brain natriuretic peptide, proBNP)分解成无活性的N端前BNP。国外研究[6]显示,NT-proBNP在 ADHF患者长期及短期预后均有预测价值,但国内采用NT-proBNP联合ST2评价心衰患者预后的研究较少。为此,本研究拟探讨血浆NT-proBNP、血清ST2 与ADHF患者预后的关系 。

1 资料和方法

1.1 临床资料

选取2011年7月～2012年4月急诊就诊的ADHF患者,出现明显呼吸困难、肺部湿罗音(诊断符合2008 ESC AHF诊断指南标准[7])75例(心衰组),男44例,女31例,平均年龄(73±12)岁。其中扩张型心肌病7例,先天性心脏病4例,风湿性心脏病8例,老年退行性心脏病9例,冠状动脉硬化性心脏病47例。排除标准：1)急性心肌梗死、急性脑卒中或伴有恶性肿瘤的终末期患者,2)有明显肝或肾脏原发疾病的心衰患者,3)有自身免疫疾病、急性创伤、急慢性感染或变态反应性疾病者,4)妊娠者。心衰组患者均经吸氧、镇静、利尿、减轻心脏负荷及强心等治疗(符合2010年心衰治疗指南[8])。选取同期我院健康体检者42例为对照组,男20例,女22例,平均年龄(67±10)岁,均无各种急、慢性疾病史。两组年龄、性别构成比等一般资料比较,差异无统计学意义(P>0.05),具有可比性(见表1)。

1.2 方法

1.2.1 资料收集 记录研究对象的性别、年龄及病史,入院或体检时的收缩压、舒张压、心率及肺部罗音。心衰组的出院转归及180 d事件发生(包括心脏性死亡、非致死性心梗、卒中、反复发作心绞痛住院、心衰住院、冠脉血运重建及其他原因死亡情况等),根据预后又将心衰组分为事件组30例及非事件组45例。

1.2.2 指标检测 心衰组入院或对照组体检时均取外周静脉血5 mL置于无热原和内毒素的试管中,以3 000 r/min离心10 min后分离血清,低温(-86 ℃)保存以集中检测。采用ALP标记的化学发光酶联免疫结合磁珠分离技术测定血浆NT-proBNP、CK-MB和cTnI水平,应用双抗体夹心法测定血清ST2浓度,所有受试对象均行常规超声心动图检查,按Simpson's法测左室射血分数(LVEF),取3个心动周期的均值,进行统计学处理。

1.3 统计学方法

2 结果

2.1 心衰组和对照组临床特征、实验室指标比较

两组在性别、年龄方面比较,差异无统计学意义(P>0.05)；但心衰组收缩压、ST2和NT-proBNP明显高于对照组,差异有显著统计学意义(P<0.01)(见表1)。

表1 心衰组和对照组临床特征、实验室指标比较

2.2 事件组与非事件组比较

心衰组患者根据预后分为事件组30例及非事件组45例,事件组患者入院时NT-proBNP、ST2和cTnI均高于非事件组,差异有统计学意义(P<0.05或<0.01)(见表2)。

表2 事件组及非事件组NT-proBNP、ST2、cTnI指标比较

2.3 相关性分析

心衰组的NT-proBNP、ST2 呈显著正相关(r=0.55,P<0.01), NT-proBNP、ST2、cTnI与事件发生呈正相关,EF值呈负相关(见表3)。

表3 心衰组各参数与预后的相关性分析

2.4 影响因素筛选

心衰组总体终点事件发生率为16.23%,将与其有相关性的参数进行Logistic回归分析发现,NT-proBNP、ST2是不良预后的独立预测因子(P<0.01)(见表4)。

表4 NT-proBNP、ST2与心衰患者总体事件发生的风险的Logistic回归分析

3 讨论

ADHF是指由于心脏结构或功能异常,引起心排量急剧降低,导致组织器官低灌注和急性淤血的一组临床综合征。近年来,ADHF的预后有所改善,但发病率和病死率仍然很高, 是内科年龄≥60岁住院患者死亡的重要原因,故应对ADHF患者进行充分的危重程度及预后评估。

ST2基因是1989年由Tominaga等[1]首先在BALB/c-3T3细胞系中获得,该基因编码产生两种蛋白: 跨膜性ST2蛋白(ST2L)和sST2。ST2L蛋白由免疫球蛋白结构域、跨膜部分和胞浆结构域3部分组成,它主要与其特异性配体IL-33结合,参与构成IL-33受体复合物[9-11]。sST2缺乏跨膜和胞浆结构域,但含有由9个氨基酸组成的独特C端序列[12]。据报道[2,13,14],sST2可作为一种诱骗受体,以剂量依赖的方式中和IL-33,阻止其与ST2L结合,从而抑制 IL-33 /ST2L信号通路抗动脉粥样硬化和心肌重构的作用。sST2属于反映心肌负荷情况的生化标志物,并且被证明在心力衰竭的诊断和治疗中具有较高的预测价值,可以提供危险分层和预后信息[15]。BNP是一种含32个氨基酸的多肽,由心房和心室共同分泌,而左心室是最主要的分泌场所。BNP分泌时,由前BNP分解成无活性的N端前BNP和有分泌活性的BNP。BNP具有扩张血管、拮抗肾素、抑制交感神经活性、促进尿钠排泄和减少水钠潴留等作用,并可特异地调节心室收缩功能和压力负荷。研究[16]显示,BNP和其他内分泌激素相比,更能反映心脏的功能。NT-pro-BNP是BNP激素原分裂后的N一端片断,两者血浆浓度具有很好的相关性。有学者[17]认为,NT-proBNP比BNP更能反映心功能受损的情况。据研究[18-20]报道,NT-proBNP可预测心衰入院后60 d、出院后6个月和1年的病死率。

本研究显示,心衰组患者NT-proBNP、ST2显著高于对照组,并且ST2与目前公认的反映心功能的指标NT-proBNP 之间明显正相关,提示ST2在ADHF患者心功能的评价有临床价值。本研究对心衰患者进行Logistic回归分析显示,NT-proBNP、ST2水平升高是急性失代偿性心衰患者180 d死亡及心脏事件的危险预测因素。因此,联合检测NT-proBNP、ST2水平有助于准确评估ADHF患者预后。

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The Plasma NT-proBNP and Serum ST2 of Acute Decompensated Heart Failure Patients for Evaluation of Prognosis

HEMing-yi,QINJian*

(DepartmentofEmergency,XuanwuHospitalofCapitalUniversityofMedicalSciences,Beijing100053,China)

Objective To study plasma NT-proBNP and serum ST2 of acute decompensated heart failure patients (ADHF) for evaluation of the prognosis. Methods Seventy-five patients with ADHF (HF group) were selected from July 2011 to April 2012 in the emergency department. Patients were divided according to the prognosis into the events of 30 cases, the non-events of 45 patients, and 42 normal healthy people were used as controls. Their plasma levels of NT-proBNP and serum levels of ST2,as well as plasma levels of CK-MB,cTnI were measured and echocardiography were perforomed and compared. Results The NT-proBNP and ST2,of ADHF group were higher than the control group (P<0.01). In events group. NT-proBNP, ST2, and cTnI were higher than the non-events group (P<0.01 orP<0.05). NT-proBNP, ST2 and cTnI were positively correlated with the outcome. Logistic regression showed that NT-proBNP was B=1.61,P<0.01,OR=4.43,95%CI=2.20-10.98 and ST2 was B=1.7,P<0.01,OR=2.03,95%CI=1.47-4.16. Conclusion High level of NT-proBNP and ST2 are risk factors for adverse outcomes in patients with ADHF.

Acute Decompensated Heart Failure; N-Terminal Probrain Natriuretic Peptides; ST2; Prognosis

秦俭, E-mail：evahe1977@sina.com

http://www.cnki.net/kcms/detail/51.1705.R.20140415.1051.007.html

10.3969/j.issn.1674-2257.2014.02.009

R541.6+1

A