肝细胞生长因子、生长分化因子-15对慢性心力衰竭的诊断和预后价值

The diagnostic and prognostic value of hepatocyte growth factor and growth differentiation factor-15 in the patients with chronic heart failure

目的探讨血清肝细胞生长因子(HGF)、生长分化因子-15(GDF-15)水平对慢性心力衰竭(CHF)的诊断和预后价值。方法选取150例CHF患者作为心衰组,根据纽约心脏病学会(NYHA)心功能分级进一步分为NYHA II级亚组、NYHA III级亚组、NYHA IV级亚组;根据原发病病因分为缺血性心衰(IHF)亚组、非缺血性心衰(NIHF)亚组。选取健康人28例为对照组。检测血清HGF、GDF-15水平;测定脑钠肽(BNP)水平,测定左室射血分数(LVEF)、左室舒张末期内径(LVEDd)。对CHF组患者随访6个月,记录CHF不良事件。通过西雅图心衰模型(SHFM)计算CHF组患者平均生存年。结果与对照组相比,心衰组血清HGF、GDF-15、BNP、LVEDd明显升高,LVEF明显降低(P <0. 05)。HGF、GDF-15随着NYHA心功能分级增加而明显升高(P <0. 05)。与NIHF亚组相比,IHF亚组HGF升高更明显(P <0. 05)。血清HGF、GDF-15水平与BNP、LVEDd、NYHA心功能分级呈正相关性(r=0. 47、0. 34,0. 42、0. 33,0. 85、0. 74,P<0. 05),与LVEF、SHFM生存年呈负相关性(r=-0. 49、-0. 45,-0. 27、-0. 30,P <0. 05)。受试者工作特性(ROC)曲线显示,血清HGF、GDF-15对CHF诊断的曲线下面积(AUC)分别是0. 886、0. 862,两者联合AUC为0. 891,HGF、GDF-15、BNP三者联合AUC为0. 898 (P <0. 05)。血清HGF、GDF-15诊断IHF的AUC分别是0. 757、0. 458 (P <0. 05)。血清HGF、GDF-15对CHF不良事件预测的AUC分别是0. 843、0. 817,HGF、GDF-15两者联合AUC为0. 873,HGF、GDF-15、BNP三者联合AUC为0. 911 (P <0. 05)。血清HGF、GDF-15对IHF、NIHF亚组的CHF不良事件预测的AUC是0. 806、0. 488,0. 481、0. 429 (P <0. 05)。结论 CHF患者血清HGF、GDF-15水平明显升高,提示心功能恶化,临床预后不良;基础心脏疾病为IHF的CHF患者,血清HGF水平升高更为明显,提示血清HGF对CHF患者基础心脏疾病的鉴别诊断具有一定价值;多指标的联合可提高对CHF的诊断和预测价值。

Objective To investigate the diagnostic and prognostic value of hepatocyte growth factor(HCF)and growth differentiation factor-15(GDF-15)in the patients with chronic heart failure(CHF).Methods One hundred and fifty CHF patients were selected as the CHF group.According to the New York Heart Association(NYHA)classification of cardiac function,the CHF group was divided into three groups,including NYHAⅡsubgroup,NYHAⅢsubgroup,NYHA IV subgroup,and according to the underlying disease type,the CHF group was divided into two groups,including ischemic heart failure(IHF)subgroup,non-ischemic heart failure(NIHF)subgroup.Twenty eight healthy people were selected as the control group.Serum HGF,GDF-15 and brain natriuretic peptide(BNP)levels were detected by ELISA.Left ventricular ejection fraction(LVEF)and left ventricular end-diastolic diameter(LVEDd)were detected by echocardiography.The CHF group patients were followed up for 6 months and CHF adverse events were recorded finally,the mean survival years was calculated using the Seattle Heart Failure Model(SHFM).Results Compared with the normal group,the serum levels of HGF,GDF-15,BNP and LVEDd were significantly higher and LVEF were lower in the CHF group(P<0.05).Furthermore,the HGF and GDF-15 levels increase along with NYHA functional classification(P<0.05).Compared with NIHF group,the serum levels of HGF were higher in IHF group significantly.The levels of serum HGF and GDF-15 were positively correlated with BNP,LVEDd and NYHA functional classifications(r=0.47,0.34,0.42,0.33,0.85,0.74,P<0.05),and negatively correlated with LVEF and SHFM survival years(r=-0.49,-0.45,-0.27,-0.30,P<0.05).The ROC curve showed that the AUC of HGF and GDF-15 in diagnosis of CHF were 0.886 and 0.862.The combined AUC was 0.891.The combined AUC of HGF,GDF-15,and BNP was 0.898(P<0.05).The AUC of HGF and GDF-15 in diagnosis of IHF and NIHF were 0.757,0.458(P<0.05).The AUC of HGF and GDF-15 in predicting CHF adverse events were 0.843 and 0.817,and the combined AUC was 0.873.The combined AUC of HGF,GDF-15 and BNP was 0.911(P<0.05).The AUC of serum HGF and GDF-15 in predicting CHF adverse events in IHF and NIHF groups were 0.806,0.488,0.481,and 0.429(P<0.05).Conclusion The levels of serum HGF and GDF-15 in patients with CHF are significantly higher,suggesting that deterioration of cardiac function and poor clinical prognosis.The level of serum HGF are significantly higher in IHF group,suggesting a certain value for the differential diagnosis of basic heart disease in CHF patients.Combination of multiple indicators can improve the value of diagnosis and prediction of CHF.It is suggested that serum HGF is valuable for the differential diagnosis of basic heart disease in CHF patients.