生长分化因子 15 在慢性心力衰竭中的作用：来自 HF-ACTION 研究的新见解。生长分化因子 15 是一种氧化应激和炎症的标志物。
Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure: Insights From the HF-ACTION Study.
机构信息
Duke Clinical Research Institute, Durham, North Carolina.
Division of Cardiology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina.
出版信息
JACC Heart Fail. 2017 Oct;5(10):724-734. doi: 10.1016/j.jchf.2017.07.013.
OBJECTIVES
This study sought to determine the relationship between growth differentiation factor (GDF)-15 and clinical outcomes in ambulatory patients with heart failure and reduced ejection fraction (HFrEF).
BACKGROUND
The prognostic utility of GDF-15, a member of the transforming growth factor-β cytokine family, among patients with HF is unclear.
METHODS
We assessed GDF-15 levels in 910 patients enrolled in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial, a randomized clinical trial of exercise training in patients with HFrEF. Median follow-up was 30 months. Cox proportional hazard models assessed the relationships between GDF-15 and clinical outcomes.
RESULTS
The median GDF-15 concentration was 1,596 pg/ml. Patients in the highest tertile of GDF-15 were older and had measurements of more severe HF (higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentrations and lower peak oxygen uptake on cardiopulmonary exercise testing [CPX]). GDF-15 therapy was a significant predictor of all-cause death (unadjusted hazard ratio [HR]: 2.03 when GDF-15 was doubled; p < 0.0001). This association persisted after adjustment for demographic and clinical and biomarkers including high sensitivity troponin T (hs-TnT) and NT-proBNP (HR: 1.30 per doubling of GDF-15; p = 0.029). GDF-15 did not improve discrimination (as measured by changes in c-statistics and the integrated discrimination improvement) in addition to baseline variables, including hs-TnT and NT-proBNP or variables found in CPX testing.
CONCLUSIONS
In demographically diverse, well-managed patients with HFrEF, GDF-15 therapy provided independent prognostic information in addition to established predictors of outcomes. These data support a possible role for GDF-15 in the risk stratification of patients with chronic HFrEF. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437).
目的
本研究旨在确定生长分化因子（GDF）-15 与射血分数降低的心力衰竭（HFrEF）门诊患者临床结局之间的关系。
背景
GDF-15 是转化生长因子-β细胞因子家族的成员，其在心力衰竭患者中的预后作用尚不清楚。
方法
我们评估了 HF-ACTION 试验（心力衰竭：一项评估运动训练对患者结局影响的对照试验）中 910 例患者的 GDF-15 水平，该试验是一项 HFrEF 患者运动训练的随机临床试验。中位随访时间为 30 个月。Cox 比例风险模型评估了 GDF-15 与临床结局之间的关系。
结果
GDF-15 浓度的中位数为 1596pg/ml。GDF-15 浓度最高三分位的患者年龄更大，且具有更严重 HF 的测量值（更高的氨基末端 B 型利钠肽前体 [NT-proBNP]浓度和心肺运动试验 [CPX]时更低的峰值摄氧量）。GDF-15 治疗是全因死亡的显著预测因素（未调整的危险比 [HR]：当 GDF-15 加倍时为 2.03；p<0.0001）。该相关性在调整人口统计学、临床和生物标志物（包括高敏肌钙蛋白 T [hs-TnT]和 NT-proBNP）后仍然存在（GDF-15 每加倍一次的 HR：1.30；p=0.029）。除了基线变量（包括 hs-TnT 和 NT-proBNP 或 CPX 检测中发现的变量）外，GDF-15 并未改善判别能力（以变化的 C 统计量和综合判别改善来衡量）。
结论
在人口统计学上多样化、管理良好的 HFrEF 患者中，GDF-15 治疗除了提供结局的既定预测因素外，还提供了独立的预后信息。这些数据支持 GDF-15 在慢性 HFrEF 患者风险分层中的可能作用。（心力衰竭：一项评估运动训练对患者结局影响的对照试验 [HF-ACTION]；NCT00047437）。
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