Portal de investigação
Growth differentiation factor-15 and the effect of empagliflozin in heart failure: Findings from the EMPEROR program
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Packer, M
- Butler, J
- Filippatos, G
- Pocock, SJ
- Januzzi, JL
- Sattar, N
- Maldonado, SG
- Panova-Noeva, M
- Sumin, M
- Masson, S
- Anker, SD
- Zannad, F
Unidades de investigação
Abstract
Aims Growth differentiation factor-15 (GDF-15) is upregulated in part in response to cardiomyocyte stretch and stress, and it exerts a protective role that is mediated by its action to suppress signalling through insulin-like growth factor (IGF) and enhance signalling through adenosine monophosphate-activated protein kinase (AMPK). Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcomes in heart failure, which has been experimentally linked to AMPK. This study aimed at evaluating the associations of GDF-15 with baseline characteristics, the prognostic significance of GDF-15, and the effect of empagliflozin on GDF-15 in patients with heart failure with a reduced and preserved ejection fraction. Methods and results Growth differentiation factor-15 was determined in serum samples from the EMPEROR-Reduced and EMPEROR-Preserved trials. Cox regression and mixed models for repeated measures were used to study the association with outcomes and the effect of empagliflozin on GDF-15, respectively. We studied 1124 patients (560 placebo and 564 empagliflozin) with median GDF-15 levels at baseline of 2442 (interquartile range 1603-3780) pg/ml. Patients with higher GDF-15 levels were typically older men with more severe symptoms, higher N-terminal pro-B-type natriuretic peptide levels, worse kidney function and who were prescribed metformin. Baseline levels of GDF-15 were well correlated with levels of IGF-binding protein 7 (rho = 0.64). Higher levels of GDF-15 were independently associated with an increased risk of cardiovascular death, heart failure hospitalizations, and worse kidney outcomes. When considered as a continuous variable, for each doubling in GDF-15, the adjusted hazard ratio for cardiovascular death or heart failure hospitalization was 1.40 (95% confidence interval 1.15-1.71; p < 0.001). The relative effect of empagliflozin on cardiovascular death and hospitalization for heart failure was most pronounced in patients with higher baseline levels of GDF-15 (interaction p-trend = 0.031). At week 52, when compared with placebo, empagliflozin increased GDF-15 by an additional 8% (p = 0.020), an effect that was primarily seen in patients not receiving metformin, a known AMPK activator. Conclusions Growth differentiation factor-15 is a marker of worse heart failure severity, is an independent predictor of major heart failure outcomes and may be associated with more pronounced benefits of empagliflozin. GDF-15 is increased among metformin users, and empagliflozin was associated with an increase in GDF-15 levels, primarily in patients not receiving metformin.
Dados da publicação
- ISSN/ISSNe:
- 1388-9842, 1879-0844
- Tipo:
- Article
- Páginas:
- 155-164
- DOI:
- 10.1002/ejhf.3078
- Link para outro recurso:
- www.scopus.com
European Journal of Heart Failure Wiley-Blackwell
Citações Recebidas na Web of Science: 9
Citações Recebidas na Scopus: 9
Documentos
- Não há documentos
Filiações
Keywords
- Growth differentiation factor-15; Heart failure; Empagliflozin; Metformin
Financiamento
Proyectos asociados
Dapagliflozin, Spironolactone or Both for HFpEF (SOGALDI-PEF) - NCT05676684
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (SOGALDI-PEF) . AstraZeneca . 2022
Initiation of ARNi and SGLT2i in Patients With HFrEF: Randomized Open-label Trial (INITIATE-HFrEF) -NCT05989503
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (INITIATE-HFrEF) . Novartis . 2023
Citar a publicação
Ferreira JP,Packer M,Butler J,Filippatos G,Pocock SJ,Januzzi JL,Sattar N,Maldonado SG,Panova M,Sumin M,Masson S,Anker SD,Zannad F. Growth differentiation factor-15 and the effect of empagliflozin in heart failure: Findings from the EMPEROR program. Eur. J. Heart Fail. 2024. 26. (1):p. 155-164. IF:18,200. (1).
