血漿NT-proBNP、血清ST2與急性失代償性心力衰竭預(yù)后評(píng)估

賀明軼,秦儉(首都醫(yī)科大學(xué)宣武醫(yī)院急診科,北京 100053)

·論 著·

血漿NT-proBNP、血清ST2與急性失代償性心力衰竭預(yù)后評(píng)估

賀明軼,秦儉*
(首都醫(yī)科大學(xué)宣武醫(yī)院急診科,北京 100053)

目的 觀察急性失代償性心力衰竭(ADHF)患者血漿NT-proBNP和血清ST2水平變化,探討其與ADHF患者預(yù)后的關(guān)系。方法 選取2011年7月～2012年4月期間急診科就診的ADHF患者75例(心衰組), 根據(jù)預(yù)后分為事件組30例及非事件組45例；選取同期健康體檢者42例為對(duì)照組。檢測(cè)并比較血漿NT-proBNP、血清ST2、CK-MB、cTnI及超聲心動(dòng)圖等指標(biāo)。 結(jié)果 ADHF患者NT-proBNP、ST2均高于對(duì)照組(P<0.01)；事件組NT-proBNP、ST2和cTnI均高于非事件組(P<0.01或P<0.05)；NT-proBNP、ST2和cTnI與預(yù)后呈正相關(guān)。Logistic回歸分析顯示,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)]是不良預(yù)后的獨(dú)立預(yù)測(cè)因子。結(jié)論 NT-proBNP、ST2水平升高是ADHF患者不良預(yù)后的危險(xiǎn)因素。

急性失代償性心力衰竭；NT-proBNP；ST2；預(yù)后

急性失代償性心力衰竭(acute decompensated heart failure, ADHF)臨床上以突發(fā)嚴(yán)重的呼吸困難為首要癥狀,可表現(xiàn)為急性肺水腫或心源性休克,嚴(yán)重時(shí)甚至危及生命。ST2蛋白是白介素-1受體家族成員之一, 其基因的發(fā)現(xiàn)可追溯到 1989 年小鼠成纖維細(xì)胞的研究[1]。ST2 基因主要編碼兩個(gè)差異性剪切產(chǎn)物,即血清可溶性 ST2 蛋白(sST2) 和跨膜性 ST2 蛋白(ST2L)。ST2是生物機(jī)械應(yīng)力產(chǎn)生的一種心肌蛋白,可由心肌成纖維細(xì)胞及心肌細(xì)胞表達(dá)[2]。近年來國外多個(gè)研究[3-5]均肯定了ST2在心功能不全診斷、嚴(yán)重程度及預(yù)后評(píng)價(jià)方面的價(jià)值。NT-proBNP(N-terminal-probrain natriuretic peptide, NT-proBNP)是由前BNP(pro brain natriuretic peptide, proBNP)分解成無活性的N端前BNP。國外研究[6]顯示,NT-proBNP在 ADHF患者長(zhǎng)期及短期預(yù)后均有預(yù)測(cè)價(jià)值,但國內(nèi)采用NT-proBNP聯(lián)合ST2評(píng)價(jià)心衰患者預(yù)后的研究較少。為此,本研究擬探討血漿NT-proBNP、血清ST2 與ADHF患者預(yù)后的關(guān)系 。

1 資料和方法

1.1 臨床資料

選取2011年7月～2012年4月急診就診的ADHF患者,出現(xiàn)明顯呼吸困難、肺部濕羅音(診斷符合2008 ESC AHF診斷指南標(biāo)準(zhǔn)[7])75例(心衰組),男44例,女31例,平均年齡(73±12)歲。其中擴(kuò)張型心肌病7例,先天性心臟病4例,風(fēng)濕性心臟病8例,老年退行性心臟病9例,冠狀動(dòng)脈硬化性心臟病47例。排除標(biāo)準(zhǔn)：1)急性心肌梗死、急性腦卒中或伴有惡性腫瘤的終末期患者,2)有明顯肝或腎臟原發(fā)疾病的心衰患者,3)有自身免疫疾病、急性創(chuàng)傷、急慢性感染或變態(tài)反應(yīng)性疾病者,4)妊娠者。心衰組患者均經(jīng)吸氧、鎮(zhèn)靜、利尿、減輕心臟負(fù)荷及強(qiáng)心等治療(符合2010年心衰治療指南[8])。選取同期我院健康體檢者42例為對(duì)照組,男20例,女22例,平均年齡(67±10)歲,均無各種急、慢性疾病史。兩組年齡、性別構(gòu)成比等一般資料比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性(見表1)。

1.2 方法

1.2.1 資料收集 記錄研究對(duì)象的性別、年齡及病史,入院或體檢時(shí)的收縮壓、舒張壓、心率及肺部羅音。心衰組的出院轉(zhuǎn)歸及180 d事件發(fā)生(包括心臟性死亡、非致死性心梗、卒中、反復(fù)發(fā)作心絞痛住院、心衰住院、冠脈血運(yùn)重建及其他原因死亡情況等),根據(jù)預(yù)后又將心衰組分為事件組30例及非事件組45例。

1.2.2 指標(biāo)檢測(cè) 心衰組入院或?qū)φ战M體檢時(shí)均取外周靜脈血5 mL置于無熱原和內(nèi)毒素的試管中,以3 000 r/min離心10 min后分離血清,低溫(-86 ℃)保存以集中檢測(cè)。采用ALP標(biāo)記的化學(xué)發(fā)光酶聯(lián)免疫結(jié)合磁珠分離技術(shù)測(cè)定血漿NT-proBNP、CK-MB和cTnI水平,應(yīng)用雙抗體夾心法測(cè)定血清ST2濃度,所有受試對(duì)象均行常規(guī)超聲心動(dòng)圖檢查,按Simpson's法測(cè)左室射血分?jǐn)?shù)(LVEF),取3個(gè)心動(dòng)周期的均值,進(jìn)行統(tǒng)計(jì)學(xué)處理。

1.3 統(tǒng)計(jì)學(xué)方法

2 結(jié)果

2.1 心衰組和對(duì)照組臨床特征、實(shí)驗(yàn)室指標(biāo)比較

兩組在性別、年齡方面比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05)；但心衰組收縮壓、ST2和NT-proBNP明顯高于對(duì)照組,差異有顯著統(tǒng)計(jì)學(xué)意義(P<0.01)(見表1)。

表1 心衰組和對(duì)照組臨床特征、實(shí)驗(yàn)室指標(biāo)比較

2.2 事件組與非事件組比較

心衰組患者根據(jù)預(yù)后分為事件組30例及非事件組45例,事件組患者入院時(shí)NT-proBNP、ST2和cTnI均高于非事件組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05或<0.01)(見表2)。

表2 事件組及非事件組NT-proBNP、ST2、cTnI指標(biāo)比較

2.3 相關(guān)性分析

心衰組的NT-proBNP、ST2 呈顯著正相關(guān)(r=0.55,P<0.01), NT-proBNP、ST2、cTnI與事件發(fā)生呈正相關(guān),EF值呈負(fù)相關(guān)(見表3)。

表3 心衰組各參數(shù)與預(yù)后的相關(guān)性分析

2.4 影響因素篩選

心衰組總體終點(diǎn)事件發(fā)生率為16.23%,將與其有相關(guān)性的參數(shù)進(jìn)行Logistic回歸分析發(fā)現(xiàn),NT-proBNP、ST2是不良預(yù)后的獨(dú)立預(yù)測(cè)因子(P<0.01)(見表4)。

表4 NT-proBNP、ST2與心衰患者總體事件發(fā)生的風(fēng)險(xiǎn)的Logistic回歸分析

3 討論

ADHF是指由于心臟結(jié)構(gòu)或功能異常,引起心排量急劇降低,導(dǎo)致組織器官低灌注和急性淤血的一組臨床綜合征。近年來,ADHF的預(yù)后有所改善,但發(fā)病率和病死率仍然很高, 是內(nèi)科年齡≥60歲住院患者死亡的重要原因,故應(yīng)對(duì)ADHF患者進(jìn)行充分的危重程度及預(yù)后評(píng)估。

ST2基因是1989年由Tominaga等[1]首先在BALB/c-3T3細(xì)胞系中獲得,該基因編碼產(chǎn)生兩種蛋白: 跨膜性ST2蛋白(ST2L)和sST2。ST2L蛋白由免疫球蛋白結(jié)構(gòu)域、跨膜部分和胞漿結(jié)構(gòu)域3部分組成,它主要與其特異性配體IL-33結(jié)合,參與構(gòu)成IL-33受體復(fù)合物[9-11]。sST2缺乏跨膜和胞漿結(jié)構(gòu)域,但含有由9個(gè)氨基酸組成的獨(dú)特C端序列[12]。據(jù)報(bào)道[2,13,14],sST2可作為一種誘騙受體,以劑量依賴的方式中和IL-33,阻止其與ST2L結(jié)合,從而抑制 IL-33 /ST2L信號(hào)通路抗動(dòng)脈粥樣硬化和心肌重構(gòu)的作用。sST2屬于反映心肌負(fù)荷情況的生化標(biāo)志物,并且被證明在心力衰竭的診斷和治療中具有較高的預(yù)測(cè)價(jià)值,可以提供危險(xiǎn)分層和預(yù)后信息[15]。BNP是一種含32個(gè)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場(chǎng)所。BNP分泌時(shí),由前BNP分解成無活性的N端前BNP和有分泌活性的BNP。BNP具有擴(kuò)張血管、拮抗腎素、抑制交感神經(jīng)活性、促進(jìn)尿鈉排泄和減少水鈉潴留等作用,并可特異地調(diào)節(jié)心室收縮功能和壓力負(fù)荷。研究[16]顯示,BNP和其他內(nèi)分泌激素相比,更能反映心臟的功能。NT-pro-BNP是BNP激素原分裂后的N一端片斷,兩者血漿濃度具有很好的相關(guān)性。有學(xué)者[17]認(rèn)為,NT-proBNP比BNP更能反映心功能受損的情況。據(jù)研究[18-20]報(bào)道,NT-proBNP可預(yù)測(cè)心衰入院后60 d、出院后6個(gè)月和1年的病死率。

本研究顯示,心衰組患者NT-proBNP、ST2顯著高于對(duì)照組,并且ST2與目前公認(rèn)的反映心功能的指標(biāo)NT-proBNP 之間明顯正相關(guān),提示ST2在ADHF患者心功能的評(píng)價(jià)有臨床價(jià)值。本研究對(duì)心衰患者進(jìn)行Logistic回歸分析顯示,NT-proBNP、ST2水平升高是急性失代償性心衰患者180 d死亡及心臟事件的危險(xiǎn)預(yù)測(cè)因素。因此,聯(lián)合檢測(cè)NT-proBNP、ST2水平有助于準(zhǔn)確評(píng)估ADHF患者預(yù)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

秦儉, 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