Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
Department of Cardiology, Institute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic; Center for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
Can J Cardiol. 2019 Apr;35(4):462-470. doi: 10.1016/j.cjca.2018.12.027. Epub 2018 Dec 26.
Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m).
A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function.
Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model.
In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.
生长分化因子 15（GDF-15）是一种应激诱导的细胞因子，也是转化生长因子-β细胞因子超家族的成员，它可以细化心力衰竭（HF）亚组患者的预后评估。我们评估了它在伴有慢性肾脏病（CKD，估计肾小球滤过率<60 mL/min/1.73 m）的 HF 患者中的作用。
共 358 例稳定收缩性 HF 患者接受中位随访 1121（四分位间距，379-2600）天。在研究入组时进行了包括 B 型利钠肽（BNP）和 GDF-15 检测的综合评估；根据肾功能进行分层分析。
CKD 患者（33.8%）年龄较大，更常患有糖尿病，较少接受血管紧张素转换酶抑制剂（ACEi）/血管紧张素受体阻滞剂（ARB）治疗。GDF-15 与估计肾小球滤过率相关，而 BNP 与左心室舒张末期直径和射血分数相关（P<0.01）。随访期间，244 例患者（68.2%）发生不良结局（死亡、紧急移植、机械循环支持植入）。在 HF 合并 CKD 患者中，Cox 比例风险模型确定 BNP、GDF-15、性别、收缩压、钠、总胆固醇和 ACEi/ARB 治疗是与不良结局相关的显著变量（P<0.05）。多变量分析中，BNP 被 GDF-15 取代。净重新分类改善证实了包含 GDF-15（GDF-15、钠、总胆固醇、ACEi/ARB 治疗）的模型优于不包含 GDF-15（BNP、性别、钠、ACEi/ARB 治疗）的模型的预后优势，净重新分类改善 0.62，P=0.005。相反，在 HF 合并正常肾功能的患者中，在多变量模型中 BNP 仍优于 GDF-15。
在伴有收缩性 HF 和 CKD 的患者中，GDF-15 与不良结局的相关性强于常规使用的 BNP。
