血清Endostatin、CTRP3、FGF21与射血分数保留心力衰竭患者临床疗效及预后的关系

The relationship between serum Endostatin,CTRP3,FGF21 and clinical efficacy and prognosis of heart failure patients with preserved ejection fraction

目的探讨血清内皮抑素(Endostatin)、补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)、成纤维细胞生长因子21(FGF21)与射血分数保留的心力衰竭(HFpEF)患者临床疗效的关系及预测预后不良的价值。方法选择2019年5月—2022年2月长沙市第三医院/湖南中医药大学附属长沙医院心血管内科收治的HFpEF患者158例(HFpEF组)和体检心功能正常的志愿者107例(健康对照组)。HFpEF患者接受常规抗心力衰竭治疗,根据疗效分为有效亚组122例和无效亚组36例,随访的152例患者根据预后情况分为预后良好亚组122例和预后不良亚组30例。比较各组血清Endostatin、CTRP3、FGF21水平,不同预后HFpEF患者超声心动图特点;多因素Logistic回归分析影响HFpEF患者预后不良的危险因素,受试者工作特征(ROC)曲线分析血清Endostatin、CTRP3、FGF21预测HFpEF患者发生预后不良的价值。结果HFpEF组血清Endostatin、FGF21水平高于健康对照组,血清CTRP3水平低于健康对照组(t/P=9.585/<0.001、13.798/<0.001、42.478/<0.001)。无效亚组血清Endostatin、FGF21水平高于有效亚组,血清CTRP3水平低于有效亚组(t/P=32.125/<0.001、9.681/<0.001、21.620/<0.001)。预后不良亚组心房颤动、美国纽约心脏病协会(NYHA)Ⅳ级比例,血清Endostatin、FGF21、氨基末端脑钠肽前体(NT-proBNP)水平,二尖瓣舒张早期血流峰值(E)/舒张晚期血流峰值(A)比值、E/二尖瓣环舒张早期心肌速度(e')比值高于预后良好亚组[t(χ^(2))/P=23.149/<0.001、7.557/0.006、22.081/<0.001、5.234/<0.001、9.840/<0.001、8.216/<0.001、5.087/<0.001],血清CTRP3、左心室射血分数(LVEF)、e’低于预后良好亚组(t/P=12.597/<0.001、2.963/0.004、5.978/<0.001)。多因素Logistic回归分析结果显示,心房颤动及血清Endostatin、FGF21、NT-proBNP升高是HFpEF患者预后不良的危险因素[OR(95%CI)=2.241(1.445-3.475)、1.047(1.014-1.081)、1.034(1.005-1.063)、1.063(1.028-1.100)],CTRP3升高是其保护因素[OR(95%CI)=0.954(0.933-0.976)];血清Endostatin、CTRP3、FGF21及三者联合预测HFpEF患者预后的曲线下面积(AUC)分别为0.741、0.703、0.654、0.837,三者联合应用诊断效能较单项指标高(Z/P=3.963/<0.001、4.617/<0.001、3.422/<0.001)。结论HFpEF患者血清Endostatin、FGF21水平增高,CTRP3水平降低,与抗心力衰竭临床疗效及预后不良有关,且是HFpEF患者预后不良的危险因素。

Objective To investigate the relationship between serum endostatin,complement C1q/tumor necrosis factor related protein 3(CTRP3),fibroblast growth factor 21(FGF21)and the clinical efficacy of heart failure with preserved ejection fraction(HFpEF)and the value of predicting poor prognosis.Methods From May 2019 to February 2022,158 HFpEF patients(HFpEF group)and 107 volunteers(healthy control group)with normal cardiac function were selected from the Cardiovascular Department of Changsha Third Hospital/Changsha Hospital Affiliated to Hunan University of Traditional Chinese Medicine.Patients with HFpEF were treated with conventional anti heart failure therapy.According to the efficacy,they were divided into 122 effective subgroups and 36 ineffective subgroups.152 follow-up patients were divided into 122 good prognosis subgroups and 30 poor prognosis subgroups according to the prognosis.The levels of serum Endostatin,CTRP3 and FGF21 in each group were compared,and the echocardiographic characteristics of HFpEF patients with different prognosis were compared;Multivariate logistic regression analysis was used to analyze the risk factors affecting the poor prognosis of HFpEF patients.The subjects'work characteristic curve(ROC)was used to analyze the value of serum Endostatin,CTRP3,FGF21 in predicting the poor prognosis of HFpEF patients.Results The serum Endostatin and FGF21 levels in HFpEF group were higher than those in healthy control group,while the serum CTRP3 levels were lower than those in healthy control group(t/P=9.585/<0.001,13.798/<0.001,42.478/<0.001).The level of serum Endostatin and FGF21 in the ineffective subgroup was higher than that in the effective subgroup,and the level of serum CTRP3 was lower than that in the effective subgroup(t/P=32.125/<0.001,9.681/<0.001,21.620/<0.001).Atrial fibrillation,NYHA class IV ratio,serum Endostatin,FGF21,N-terminal pro brain natriuretic peptide(NT-proBNP)levels,early diastolic peak flow(E)/late diastolic peak flow(A)ratio,and early diastolic myocardial velocity(e')ratio of E/mitral annulus in the subgroup with poor prognosis were higher than those in the subgroup with good prognosis[t(χ^(2))/P=23.149/<0.001,7.557/0.006,22.081/<0.001,5.234/<0.001,9.840/<0.001,8.216/<0.001,5.087/<0.001],serum CTRP3,left ventricular ejection fraction(LVEF),e'were lower than the subgroups with good prognosis(t/P=12.597/<0.001,2.963/0.004,5.978/<0.001).Multivariate logistic regression analysis showed that atrial fibrillation and elevated serum Endostatin,FGF21,NT-proBNP were risk factors for poor prognosis of HFpEF patients[OR(95%CI)=2.241(1.445-3.475),1.047(1.014-1.081),1.034(1.005-1.063),1.063(1.028-1.100)],and elevated CTRP3 was a protective factor[OR(95%CI)=0.954(0.933-0.976)];The AUC of serum Endostatin,CTRP3,FGF21 and their combination to predict the prognosis of HFpEF patients were 0.741,0.703,0.654 and 0.837,respectively.The diagnostic efficacy of their combination was higher than that of single index(Z/P=3.963/<0.001,4.617/<0.001,3.422/<0.001).Conclusion The increase of serum Endostatin and FGF21 levels and the decrease of serum CTRP3 levels in HFpEF patients are related to the clinical efficacy of anti-heart failure and poor prognosis,and are risk factors for poor prognosis in HFpEF patients.