即时检验检测的中性粒细胞明胶酶相关脂质运载蛋白相关影响因素及其对心力衰竭预后的预测价值

Predictors of Point of Care Test-measured Neutrophil Gelatinase-associated Lipocalin and Its Predictive Value for the Prognosis of Heart Failure

目的:探讨即时检验(POCT)检测的中性粒细胞明胶酶相关脂质运载蛋白(NGAL)相关影响因素及其对心力衰竭预后的预测价值。方法:纳入2015年7月至2017年7月在中国医学科学院阜外医院心力衰竭重症监护病房住院的心力衰竭患者864例,采用POCT检测患者基线血清NGAL水平。根据基线NGAL水平三分位数分为低NGAL组(NGAL≤75.41ng/ml,n=288)、中NGAL组(75.41 ng/ml<NGAL<135.33 ng/ml,n=288)及高NGAL组(NGAL≥135.33 ng/ml,n=288),比较三组患者的一般临床资料。采用多元线性回归分析与NGAL相关的独立预测因子。采用多因素Cox回归分析、限制性立方样条图、多因素Cox回归模型风险预测检验及Kaplan-Meier生存曲线评估基线NGAL水平对心力衰竭预后的预测价值。结果:与低NGAL组、中NGAL组相比,高NGAL组患者年龄较大,血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂应用率、丙氨酸氨基转移酶、血钠水平及估算肾小球滤过率(eGFR)较低,白细胞计数、血钾、血肌酐、尿素氮、尿酸、高敏C反应蛋白及N末端B型利钠肽原(NT-proBNP)水平较高,差异均有统计学意义(P均<0.05)。多元线性回归分析显示,血钾(β=0.152,P=0.017)及血肌酐(β=0.337,P<0.001)是NGAL的独立预测因子。共117例(13.5%)患者失访,中位随访949 d时,231例(30.9%)患者死亡或接受心脏移植。多因素Cox回归分析显示,基线NGAL水平是心力衰竭患者全因死亡或接受心脏移植的独立预测因子(对数值每增加1个单位,校正后HR=1.22,95%CI:1.03~1.44,P=0.024)。限制性立方样条图分析显示,当基线NGAL>102 ng/ml时,心力衰竭患者全因死亡或接受心脏移植的风险随着NGAL水平升高而增加。多因素Cox回归模型风险预测检验结果显示,在基础模型+基线NT-proBNP基础上联用基线NGAL水平可为心力衰竭预后评估提供额外的预测价值[C指数(基础模型+NTproBNP+NGAL)0.7983 vs.C指数(基础模型+NT-proBNP)0.7973,P=0.025]。Kaplan-Meier生存曲线分析显示,三组间的生存率差异具有统计学意义(P=0.016)。结论:血钾及血肌酐是NGAL的独立预测因子。POCT检测的基线NGAL水平是心力衰竭患者全因死亡或接受心脏移植的独立预测因子,在基线NT-proBNP基础上,基线NGAL水平可提供额外的预测价值。

Objectives:To investigate the related risk factors of neutrophil gelatinase-associated lipocalin(NGAL)measured by the point of care test(POCT)and its value in predicting the prognosis of heart failure.Methods:A total of 864 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed with heart failure from July 2015 to July 2017 were enrolled.Baseline serum NGAL concentration was tested by POCT According to serum NGAL levels,patients were divided into three groups:low NGAL group(NGAL≤75.41 ng/m1.n=288),middle NGAL group(75.41 ng/m<NGAL<135.33 ng/ml,n=288)and high NGAL group(NGAL>135.33 ng/ml,n=288).The general clinical characteristics were collected and compared among the three groups.Multivariate linearregression analysis was conducted to investigate the independent risk factors of NGAL.Multivariate Cox regressionanalysis,restricted cubic spline(RCS),risk prediction test with multivariate Cox regression model and Kaplan-Meieranalysis were conducted to investigate the relationship between NGAL and the prognosis of heart faiture.Results:Compared with low and middle NGAL groups,patients in high NGAL group were older,had lower rateof angiotensin-converting enzyme inhibitors(ACEI)/angiotensinⅡreceptor blockers(ARB)treatment,lower levelsof alanine aminotransferase,sodium and estimated glomerular filtration rate(eGFR),and higher levels of white bloodcell,potassium,creatinine,blood urea nitrogen,uric acid,high sensitivity C reactive protein and N-terminal pro-B-typenatriuretic peptide(NT-proBNP)(all p<0.05).Multivariate linear regression analysis showed that potassium(B=0.152,P-0.017)and creatinine(B=0.337,P<0.001)were independent predictors of NGAL.117 patients(13.5%)were lost tofollow-up,and 231 patients(30.9%)suffered from all-cause death or heart transplantation during the median follow-upduration of 949 days.Multivariate Cox regression analysis showed that baseline NGAL was an independent predictor ofall-cause death or heart transplantation in patients with heart failture(per 1 log unit,adjusted HR=1.22,95%CI:1.03-1.44,P-0.024).RCS showed that the risk of all-cause death or heart transplantation increased significantly along withthe increase of NGAL level when NGAL concentration was more than 102 ng'm1.Risk prediction test with multivariateCox regression model showed that baseline NGAL could provide additional prognostic value for heart failture patientson top of basic model and baseline NT-proBNP(C-index[basic model+NT-proBNP+NGAL]0.7983 vs.C-index[basicmode1+NT-proBNP]0.7973,P-0.025).Kaplan-Meier analysis showed that the survival rates were significantly differentamong the three groups(P=0.016).Conclusions:Potassium and creatinine are independent predictors of NGAL.Baseline NGAL is an independentpredictor of al-cause death or heart transplantation in patients with heart failture.And baseline NGAL could provideadditional prognostic value in combination with baseline NT-proBNP in predicting adverse events for heart faiture patients.