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

Publication ,  Journal Article
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 ...
Published in: JACC. Heart failure
October 2017

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).The prognostic utility of GDF-15, a member of the transforming growth factor-β cytokine family, among patients with HF is unclear.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.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.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).

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Published In

JACC. Heart failure

DOI

EISSN

2213-1787

ISSN

2213-1779

Publication Date

October 2017

Volume

5

Issue

10

Start / End Page

724 / 734

Related Subject Headings

  • Stroke Volume
  • Severity of Illness Index
  • Randomized Controlled Trials as Topic
  • Proportional Hazards Models
  • Prognosis
  • Peptide Fragments
  • Oxidative Stress
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Male
 

Citation

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Sharma, A., Stevens, S. R., Lucas, J., Fiuzat, M., Adams, K. F., Whellan, D. J., … Felker, G. M. (2017). 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 Failure, 5(10), 724–734. https://doi.org/10.1016/j.jchf.2017.07.013
Sharma, Abhinav, Susanna R. Stevens, Joseph Lucas, Mona Fiuzat, Kirkwood F. Adams, David J. Whellan, Mark P. Donahue, et al. “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 Failure 5, no. 10 (October 2017): 724–34. https://doi.org/10.1016/j.jchf.2017.07.013.
Sharma A, Stevens SR, Lucas J, Fiuzat M, Adams KF, Whellan DJ, et al. 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 failure. 2017 Oct;5(10):724–34.
Sharma, Abhinav, et al. “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 Failure, vol. 5, no. 10, Oct. 2017, pp. 724–34. Epmc, 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. 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 failure. 2017 Oct;5(10):724–734.
Journal cover image

Published In

JACC. Heart failure

DOI

EISSN

2213-1787

ISSN

2213-1779

Publication Date

October 2017

Volume

5

Issue

10

Start / End Page

724 / 734

Related Subject Headings

  • Stroke Volume
  • Severity of Illness Index
  • Randomized Controlled Trials as Topic
  • Proportional Hazards Models
  • Prognosis
  • Peptide Fragments
  • Oxidative Stress
  • Natriuretic Peptide, Brain
  • Middle Aged
  • Male