孫 波,田紅霞,李 晟,王月娥,荊 忱,王 軍
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氨基末端腦鈉肽水平與老年血液透析合并心力衰竭死亡的相關性
孫 波1,田紅霞1,李 晟1,王月娥1,荊 忱1,王 軍2
目的 研究氨基末端腦鈉肽(N terminal-pro brain nalriuretic peptide,NT-proBNP)水平與老年維持性血液透析并充血性心力衰竭死亡的相關性。方法 選擇維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例為死亡組,心力衰竭緩解30例為非死亡組,比較住院前、住院期間死亡組和非死亡組NT-proBNP水平,采用二分類Logistic回歸分析影響死亡的相關因素,偏相關分析影響死亡組NT-proBNP水平的相關因素,受試者工作特征(ROC)曲線評價NT-proBNP水平對死亡的預測效能。結果 死亡組入院時NT-proBNP中位數(shù)為31 000 ng/L,與非死亡組入院時NT-proBNP中位數(shù)28 500 ng/L比較無統(tǒng)計學意義;死亡組住院期間NT-proBNP中位數(shù)為9200 ng/L,明顯高于非死亡組NT-proBNP中位數(shù)4700 ng/L,差異有統(tǒng)計學意義(P<0.01);二分類Logistic回歸分析提示住院期間NT-proBNP水平為影響死亡的唯一相關因素(P<0.01);左室EF值、透析間期體質量增加值、左室擴大為影響死亡組住院期間NT-proBNP水平相關因素(P<0.01)。死亡組住院期間NT-proBNP的AUC值為0.962,差異有統(tǒng)計學意義(P<0.05);NT-proBNP>7650 ng/L作為界值(Cut off值)的敏感度為82.4%,特異度為84%;非死亡組住院期間NT-proBNP的AUC值為0.038,差異無統(tǒng)計學意義。結論 老年維持性血液透析并充血性心力衰竭住院期間高水平NT-proBNP與死亡具有相關性,可作為預測死亡的指標。
維持性血液透析;氨基末端腦鈉肽;充血性心力衰竭;受試者工作特征;死亡
維持性血液透析(maintenance hemodialysis,MHD)患者心血管事件發(fā)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癥者。NT-proBNP有判斷心力衰竭程度和預后的價值[1-4],但少見預測血液透析合并CHF死亡的報告,本研究回顧性分析了氨基末端腦鈉肽水平與老年MHD并CHF死亡的相關性,旨在作為預測死亡的指標,為臨床提供依據(jù)。
1.1 對象 選擇2010-01至2015-12因終末期腎衰竭血液透析并CHF住院患者,根據(jù)是否死亡分為死亡組和非死亡組。入選標準:(1)血液透析1個月以上,每周血液透析>8 h;(2)年齡≥60歲,性別不限;(3)同時合并CHF,心功能Ⅲ級和Ⅳ級。排除標準:(1)合并肺心病、急性心肌梗死;(2)心功能Ⅰ級和Ⅱ級;(3)合并腫瘤者。用碳酸氫鹽透析液透析,3次/周,采用醋酸空心纖維透析器(NIPRO Sureflus-150G透析器),膜面積1.5 m2,血流量180~220 ml/min,透析液流量500 ml/min。CHF按美國紐約心臟病協(xié)會(New Youk Heart Association,NYHA)心功能分級。
1.2 血漿NT-proBNP測定 于入院時、住院期間分別抽取血樣,肝素鋰抗凝。測定方法:采用丹麥AQT90 FLEX快速免疫分析儀檢測,試劑由丹麥Radiometer Medical Aps提供,檢測范圍12~35 000 ng/L。1.3 左室擴大的評估 入院后行超聲心動圖檢查,測量左心室射血分數(shù)(LVEF)、左室舒張末期后壁厚度(LVPWT)、左室舒張末期室間隔厚度(IVST)、左心室舒張末期內徑(LVEDD)。LVEDD男≥5.5 cm,女≥5.0 cm診斷為左室擴大[5]。
1.4 實驗室檢查 治療前采血測定血常規(guī)、鉀鈉氯、鈣、磷、血糖、血肌酐(Scr)、尿素氮、全段甲狀旁腺素(iPTH)、白蛋白。
1.5 統(tǒng)計學處理 采用SPSS 19.0軟件進行分析。組間均數(shù)比較采用成組t檢驗;偏態(tài)分布變量用中位數(shù)(四分位數(shù)間距)表示,組間比較采用非參數(shù)檢驗,計數(shù)資料用χ2檢驗;P<0.05為差異有統(tǒng)計學意義。用二分類Logistic回歸分析和偏相關分析死亡組與死亡相關因素以及住院期間NT-proBNP水平的影響因素,用ROC曲線評價NT-proBNP水平對預測死亡的診斷效能,用AUC及95%可信區(qū)間表示。
2.1 臨床資料比較 兩組年齡、性別比和心房顫動、冠心病,心功能分級例數(shù)及舒張壓、血鉀、白蛋白、血肌酐、尿素氮、iPTH、eGFR值比較均無統(tǒng)計學意義;左室擴大例數(shù)、收縮壓、左室EF值、血紅蛋白、透析間期體質量增加量比較差異有統(tǒng)計學意義(P<0.05,表1)。
表1 心力衰竭死亡組與非死亡組臨床資料比較
項目死亡組(n=22)非死亡組(n=30)統(tǒng)計值P年齡(歲)74.10±6.4768.02±5.65t=1.271>0.05性別(男/女)15/719/11χ2=0.103>0.05左室擴大(有/無,例)16/610/20χ2=10.084<0.05心房顫動(有/無,例)6/164/26χ2=0.600>0.05冠心病(有/無,例)12/1013/17χ2=0.113>0.05心功能分級(Ⅲ級/Ⅳ級)5/1712/18χ2=1.018>0.05收縮壓(mmHg)156.03(137.75~151.25)141.50(130.4-153.8)z=-1.862<0.05舒張壓(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血鉀(mmol/L)4.21±0.674.06±0.53t=1.230>0.05血紅蛋白(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殘余尿量(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透析間期體質量增加(Kg)4.52(4.0~4.5)3.20(3.4~3.9)z=-5.756<0.01
2.2 血漿NT-proBNP水平比較結果 入院時死亡組血漿NT-proBNP值為31.0×103ng/L,非死亡組血漿NT-proBNP值為28.5×103ng/L,兩組比較差異無統(tǒng)計學意義;住院期間死亡組血漿NT-proBNP值為9.2×103ng/L,明顯高于非死亡組血漿NT-proBNP值4.7×103ng/L,差異有統(tǒng)計學意義(P<0.01)。
2.3 死亡組相關因素的Logistic回歸分析及偏相關分析結果 以死亡為因變量,選取表1中的左室擴大、收縮壓、左室EF值、Hb、透析間期體質量增加以及入院時和住院期間NT-proBNP為自變量,用二分類Logistic相關分析結果提示死亡與住院期間NT-proBNP(Wald為7.163,Exp為1.124)相關(P<0.05)。偏相關分析提示住院期間NT-proBNP與透析間期體質量增加及左室EF值、左室擴大相關(P均<0.01)。
2.4 NT-proBNP對死亡組患者死亡判定的ROC曲線診斷效能 住院期間NT-proBNP判斷老年血透并心力衰竭患者死亡的AUC值為0.962,大于0.5,差異有統(tǒng)計學意義(P<0.05);NT-proBNP>7650 ng/L作為界值(Cut off值)的敏感度82.4%,特異度84%。
MHD患者80%存在左心室肥厚、功能受損及缺血性心臟病等心血管并發(fā)癥,其不良心血管事件發(fā)生率較正常人群高20倍,病死率約占MHD患者死因的50%以上[6]。NT-proBNP是心室肌細胞在容量和壓力負荷增加時合成和分泌的多肽類神經激素,作為心血管疾病診斷、治療和預后評價的重要生物學標志物已廣泛用于心血管疾病的檢查。
本研究發(fā)現(xiàn),死亡組住院期間NT-proBNP水平明顯高于非死亡組,而且死亡組存在更多的左室擴大、高收縮壓、低的左室EF值、貧血糾正不佳、透析間期體質量增加等因素,提示這些指標是影響患者死亡的相關因素。進一步Logistic回歸分析和偏相關分析顯示住院期間高水平NT-proBNP和左室EF值、左室擴大是影響患者死亡的主要指標。有研究證明,NT-proBNP對心力衰竭診斷具有極高的敏感性和特異性,是1年死亡風險的強烈預測因素[7,8]。而且具有預測血液凈化患者生存率的意義[9,10]。Paniagua等[11]對 753 例 MHD 患者隨訪16 個月,多變量分析顯示NT-proBNP是獨立于透析模式的全因病死率及心血管病死率的預測因子。本研究發(fā)現(xiàn)住院期間NT-proBNP水平主要受透析間期體質量增加影響。文獻[12]報道導致NT-proBNP升高的各種心臟異常情況包括左心室收縮和舒張功能不全、心室大小和功能,其次與容量潴留有關。血液透析患者由于殘余尿量減少,透析間期易出現(xiàn)容量負荷增加,超出心臟代償范圍后可伴有NT-proBNP升高,甚至出現(xiàn)心力衰竭。NT-proBNP水平除反映MHD患者心功能外,也是細胞外容量擴充的標志。即NT-proBNP與容量超負荷相關,可以用于評估患者的容量負荷[13]。這些結果說明血液透析患者在左室EF值下降基礎上,透析間期體質量增加可增加心臟負荷,使心室肌張力增加,促使NT-proBNP產生增加。長期透析間期體質量增加也是誘發(fā)和加重心臟擴大、血壓高和心力衰竭的風險因素。
本研究ROC曲線分析結果提示高水平NT-proBNP作為預測因CHF死亡具有較高敏感度和特異度。將治療后的住院期間NT-proBNP水平持續(xù)大于7650 ng/L作為心血管事件及死亡預測指標有助于早期判斷老年血液透析患者充血性心力衰竭死亡風險。以往一些研究發(fā)現(xiàn)經治療后測定的出院前NT-proBNP水平比入院時NT-proBNP水平具有更高的預后評價能力[14,15]。高水平的 NT-proBNP 有較高的病死率[16]。這些研究雖然不是專門針對血液透析患者的研究,但證實持續(xù)高水平NT-proBNP是心血管意外及死亡的獨立危險因素。目前在血液透析患者這個特殊人群還沒有一個公認確定的監(jiān)測心衰和判斷預后的合適NT-proBNP水平范圍。根據(jù)上述研究結果我們認為老年維持性血液透析并充血性心力衰竭住院期間高水平NT-proBNP與死亡具有相關性,可作為預測死亡的指標。
本研究由于病例數(shù)不多,還有待今后工作中繼續(xù)觀察,期待更多前瞻性大規(guī)模臨床試驗證實并確定NT-proBNP水平范圍來指導臨床工作。
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(2016-06-12收稿 2016-09-21修回)
(責任編輯 張 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
孫 波,碩士研究生,副主任醫(yī)師。
100089 北京,解放軍航空醫(yī)學研究所附屬醫(yī)院:1.內二科,2.院辦
王 軍,E-mail:wang_jun466@sina.com
R692.5