南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (11): 1273-1279.doi: 10.12122/j.issn.1673-4254.2019.11.02

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循环单核细胞和血浆中GDF-15和NT-proBNP对慢性心力衰竭的诊断及心血管事件的预测价值

乔香瑞，刘军辉，花 蕊，卓小桢   

  • 出版日期:2019-12-05 发布日期:2019-11-20

GDF-15 in plasma and circulating mononuclear cells and NT-proBNP for diagnosis of chronic heart failure and predicting cardiovascular disease events

  • Online:2019-12-05 Published:2019-11-20

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摘要： 目的 探讨基础心脏病是扩张型心肌病（DCM）或冠心病的心力衰竭患者血浆中生长分化因子-15（GDF-15）蛋白水平和外周血单核细胞（MNCs）中GDF-15 mRNA水平，并评估它们是否能够成为心力衰竭严重程度和长期心血管事件的预测因子。方法 收集261例DCM患者，251例冠心病患者和132例无心力衰竭的健康对照空腹静脉血标本并对这些患者进行门诊随访。酶联免疫吸附实验（ELISA）检测GDF-15的血浆水平。实时聚合酶链反应检测MNCs中GDF-15 mRNA的表达水平，并对比分析GDF-15在不同NYHA分级患者中的表达情况，用ROC曲线评估GDF-15 mRNA对心血管事件的预测能力。结果 DCM和冠心病患者血浆中GDF-15水平及MNCs中GDF-15 mRNA表达水平显著高于对照组（P<0.01）。心功能Ⅳ级（NYHA）心衰患者的血浆 GDF-15水平显著高于Ⅱ和Ⅲ级患者。心功能Ⅲ级和Ⅳ级心衰患者的 MNCs中 GDF-15 mRNA水平远高于Ⅱ级患者（P<0.01）。此外，心血管事件的ROC曲线分析显示，与单独用NT-proBNP预测相比，加入GDF-15 mRNA后曲线下面积从0.73（95% CI：0.69~0.77，P<0.001）增长为0.83（95%CI：0.79~0.86，P<0.001）。结论 血浆GDF-15水平和MNCs中GDF-15 mRNA水平均可以作为心力衰竭的生物标志物，血浆中GDF-15水平对预测心功能IV级的心衰患者更为敏感，而MNCs中GDF-15 mRNA水平则更能预测心功能II级的心衰患者。NT-proBNP联合GDF-15 mRNA水平能更准确地预测长期心血管事件的发生风险。

Abstract: Objective To investigate the diagnostic value of plasma growth and differentiation factor-15 (GDF-15) level, GDF-15mRNA expression in circulating mononuclear cells (MNCs), and plasma pro-B-type natriuretic peptide (NT-proBNP) level for heart failure in patients with different underlying cardiac diseases, namely dilated cardiomyopathy (DCM) and coronary artery heart disease (CAD), and assess their value in predicting the severity of heart failure and long-term cardiovascular disease (CVD) events. Methods Fasting venous blood samples were collected from 261 patients with DCM and 251 patients with CAD admitted in our hospital between January, 2018 and January, 2019, with 132 healthy individuals serving as the control group. The plasma level of GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the expression of GDF-15 mRNA in the MNCs was measured by real-time PCR. We also analyzed the expression of GDF-15 in patients with different NYHA classes, and the ROC curve was used to evaluate the predictive power of GDF-15 mRNA for CVD events. Results The plasma levels of GDF-15 and GDF-15 mRNA in the MNCs were significantly higher in patients with DCM and CAD than in the control group (P<0.01). Plasma GDF-15 levels were significantly higher in NYHA class IV patients than in class II and III patients, and GDF-15 mRNA expressions in the MNCs were much higher in class III and IV patients than class II patients (P<0.01). ROC curve analysis showed that for predicting CVD events, the area under the curve (AUC) was 0.73 (95% CI: 0.69-0.77, P<0.001) for NT-proBNP alone, as compared with 0.83 (95% CI: 0.79-0.86, P<0.001) for GDF-15 mRNA in the MNCs combined with NT-proBNP. Conclusion Plasma GDF-15 level and GDF-15 mRNA expression level in the MNSc can both be used as biomarkers for heart failure. Plasma level of GDF-15 is more sensitive for predicting NYHA class IV patients with heart failure, while GDF-15 mRNA level in the MNCs better predicts class II patients. The combination of NT-proBNP with GDF-15 mRNAlevel in the MNCs can more accurately predict the risk of long-term CVD events.