Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure Insights From the HF-ACTION Study

作者：Sharma Abhinav; Stevens Susanna R; Lucas Joseph; Fiuzat Mona; Adams Kirkwood F; Whellan David J; Donahue Mark P; Kitzman Dalane W; Pina Ileana L; Zannad Faiez; Kraus William E; O'Connor Christopher M; Felker G Michael^*

来源：JACC-Heart Failure, 2017, 5(10): 724-734.

DOI：10.1016/j.jchf.2017.07.013

• BNP
• B-type natriuretic peptide
• heart failure
• N-terminal pro-B-type natriuretic peptide

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-beta 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.

• 出版日期2017-10