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

Overview

Journal JACC Heart Fail

Publisher Elsevier

Date 2017 Sep 30

PMID 28958347

Citations 40

Authors

Abhinav Sharma

Susanna R Stevens

Joseph Lucas

Mona Fiuzat

Kirkwood F Adams

David J Whellan

Mark P Donahue

Dalane W Kitzman

Ileana L Pina

Faiez Zannad

William E Kraus

Christopher M OConnor

G Michael Felker

Affiliations

Soon will be listed here.

Abstract

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).

Citing Articles

Combined Use of GDF-15 and NT-Pro BNP for Outcome Prediction in Patients with Acute Heart Failure.

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Association between growth differentiation factor-15 and adverse outcomes among patients with heart failure: A systematic literature review.

Javaheri A, Ozcan M, Moubarak L, Smoyer K, Rossulek M, Revkin J Heliyon. 2024; 10(16):e35916.

PMID: 39229539 PMC: 11369438. DOI: 10.1016/j.heliyon.2024.e35916.

Growth differentiation factor-15, a novel systemic biomarker of oxidative stress, inflammation, and cellular aging: Potential role in cardiovascular diseases.

di Candia A, de Avila D, Moreira G, Villacorta H, Maisel A Am Heart J Plus. 2024; 9:100046.

PMID: 38559370 PMC: 10978141. DOI: 10.1016/j.ahjo.2021.100046.

Inflammation in heart failure: pathophysiology and therapeutic strategies.

Boulet J, Sridhar V, Bouabdallaoui N, Tardif J, White M Inflamm Res. 2024; 73(5):709-723.

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Prevalence and impact of sarcopenia in individuals with heart failure with reduced ejection fraction (the SARC-HF study): A prospective observational study protocol.

Correa Nascimento P, Rodrigues Junior L, Mediano M, Goncalves da Silva V, Tura B, Nogueira F PLoS One. 2024; 19(3):e0300918.

PMID: 38512827 PMC: 10956824. DOI: 10.1371/journal.pone.0300918.

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