血清成纤维细胞生长因子21对缺血性心肌病患者的预后价值研究

The prognostic value of serum fibroblast growth factor 21 levels in patients with ischemic cardiomyopathy

目的:探讨血清成纤维细胞生长因子21(FGF21)水平对缺血性心肌病(ICM)患者预后的预测价值。方法:连续选取2016年1月至2018年12月于南通大学附属江阴医院心血管内科就诊的ICM患者及同期健康体检群众。通过酶联免疫吸附法(ELISA)检测血清FGF21水平,比较两者血清FGF21水平的差异。对ICM患者进行随访,临床终点事件包括全因死亡或再入院。计算受试者工作特征(ROC)曲线下面积(AUC),评估血清FGF21水平对ICM患者临床终点事件的预测价值,确定预测的最佳界值,根据界值将ICM患者分为FGF21高水平组和低水平组,采用Kaplan-Meier生存曲线法比较两组患者无临床终点事件生存率的差异,采用多因素Cox回归分析方法评估临床终点事件的预测因素。结果:本研究共纳入115例ICM患者,63例体检群众。ICM组患者的血清FGF21水平高于体检群众[(207.60±43.89)pg/mL比(136.86±33.48)pg/mL,P<0.001]。在ICM患者中,血清FGF21水平与N末端B型利钠肽原及超声心动图测量的左心房内径、左心室收缩末期内径呈正相关(相关系数分别为r=0.528,r=0.196和r=0.195,P均<0.05),与超声心动图测量的左心室射血分数呈负相关(r=-0.213,P<0.05)。ICM患者随访时间为25(7,56)个月,共有68例发生临床终点事件。血清FGF21预测ICM患者发生临床终点事件的AUC值为0.851(95%可信区间为0.779~0.924,P<0.001),以FGF21=209.17 pg/mL为界值分为高水平组和低水平组,Kaplan-Meier生存曲线法分析结果显示,高水平组ICM患者的无临床终点事件生存率低于低水平组(log-rank检验,P<0.001)。多因素Cox回归分析结果显示,校正其他混杂因素后,FGF21水平仍是ICM患者发生临床终点事件的独立预测因素(每升高1pg/mL,风险比为1.032,95%可信区间为1.022~1.042,P<0.001)。结论:血清FGF21水平升高对ICM患者发生全因死亡或再入院具有预测价值,是ICM患者预后不良的独立预测因素。

Objective To investigate the prognostic value of serum fibroblast growth factor 21(FGF21)levels in patients with ischemic cardiomyopathy(ICM).Methods Patients admitted to the Department of Cardiology of Jiangyin Hospital Affiliated to Nantong University from January 2016 to December 2018 with the diagnosis of ICM and the healthy people who underwent physical examination during the same period were selected.Serum FGF21 levels were tested by enzyme-linked immunosorbent assay(ELISA).Patients with ICM were followed-up and the clinical endpoint events included all-cause death and re-hospitalization.According to receiver operating characteristic curve(ROC),the area under the curve(AUC)was calculated to evaluate the predictive value of serum FGF21 for the clinical endpoint events and the optimal cutoff value was determined.According to the cutoff value of serum FGF21 level,patients with ICM were divided into higher level group and lower level group,and the difference in the incidence of clinical endpoint events between these two groups were compared by using of the Kaplan-Meier survival curve method.Moreover,multivariate Cox regression analysis was used to identify the predictors of clinical endpoint events.Results A total of 115 ICM patients and 63 healthy people were included in this study.The levels of serum FGF21 were significantly higher in ICM patients than those in healthy people[(207.60±43.89)pg/mL vs.(136.86±33.48)pg/mL,P<0.001].Among patients with ICM,serum FGF21 levels were positively correlated with serum N terminal-pro B type natriuretic peptide levels(r=0.528,P<0.05),left atrial diameter(r=0.196,P<0.05)and left ventricular end systolic diameter(r=0.195,P<0.05)measured by echocardiography,while a negative correlation was observed between serum FGF21 levels and left ventricular ejection fraction measured by echocardiography(r=-0.213,P<0.05).The follow-up time of ICM patients was 25(7,56)months and a total of 68 patients had clinical endpoint events.The AUC value of serum FGF21 for predicting clinical endpoint events in ICM patients was 0.851[95%confidence interval(CI)0.779~0.924,P<0.001]at the optimal cutoff value of serum FGF21 of 209.17 pg/mL.Kaplan-Meier survival curve analysis showed that the clinical endpoints-free survival rate in patients among the higher level group was significantly lower than those in the lower level group(log-rank test,P<0.001).Moreover,multivariate Cox regression analysis demonstrated that serum FGF21 level was an independent predictor of clinical endpoints in patients with ICM after adjusting for other confounding factors(per 1 pg/mL increase,hazard ratio 1.032,95%CI 1.022~1.042,P<0.001).Conclusions Increase of serum FGF21 level has a prognostic value for all-cause death or readmission in patients with ICM.Serum FGF21 was an independent predictor of poor prognosis in ICM patients.