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

JACC Heart Fail. 2017 Oct;5(10):724-734. doi: 10.1016/j.jchf.2017.07.013

Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ,
Donahue MP, Kitzman DW, Piña IL, Zannad F, Kraus WE, O’Connor
CM, Felker GM.

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]

American College of Cardiology Foundation