Insulin-like growth factor binding protein-7 concentrations in chronic heart failure: Results from the EMPEROR programme

Autores da FMUP

• João Pedro Melo Marques Pinho Ferreira

  Autor

Participantes de fora da FMUP

• Packer M.
• Sattar N.
• Butler J.
• González Maldonado S.
• Panova-Noeva M.
• Sumin M.
• Masson S.
• Pocock S.J.
• Anker S.D.
• Zannad F.
• Januzzi J.L.

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

Aims: Insulin-like growth factor binding protein-7 (IGFBP7) is a biomarker of tissue senescence with a role in cardio-renal pathophysiology. The role of IGFBP7 as a prognostic biomarker across the full ejection fraction (EF) spectrum of heart failure (HF) remains less well understood. We examined associations between IGFBP7 and risk of cardio-renal outcomes regardless of EF and the effect of empagliflozin treatment on IGFBP7 concentrations among individuals with HF. Methods and results: IGFBP7 was measured in 1125 study participants from the EMPEROR-Reduced and EMPEROR-Preserved trials. Cox regression was used to study associations with outcomes. Study participants with IGFBP7 levels in the highest tertile had a higher-risk clinical profile. In Cox proportional hazards models adjusted for clinical variables, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T, baseline IGFBP7 values in the highest tertile predicted an increased risk of HF hospitalization or cardiovascular death (hazard ratio [HR] 2.00, 95% confidence interval [CI] 1.28–3.10, p = 0.002, p for trend <0.001) and higher risk of the renal composite endpoint (HR 4.66, 95% CI 1.61–13.53, p = 0.005, p for trend = 0.001), regardless of EF. Empagliflozin reduced risk for cardiovascular death/HF hospitalization irrespective of baseline IGFBP7 (p for trend across IGFBP7 tertiles = 0.26). Empagliflozin treatment was not associated with meaningful change in IGFBP7 at 12 or 52 weeks. Conclusion: Across the entire left ventricular EF spectrum in the EMPEROR Programme, concentrations of the senescence-associated biomarker IGFBP7 were associated with higher risk clinical status and predicted adverse cardio-renal outcomes even in models adjusted for conventional biomarkers. Empagliflozin did not significantly affect IGFBP7 levels over time. © 2024 European Society of Cardiology.

Keywords

• Aged; Benzhydryl Compounds; Biomarkers; Female; Glucosides; Heart Failure; Humans; Insulin-Like Growth Factor Binding Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; amino terminal pro brain natriuretic peptide; angiopoietin 2; biological marker; bone morphogenetic protein; bone morphogenetic protein 10; CA 125 antigen; empagliflozin; fatty acid binding protein 3; insulin like growth factor binding protein7; somatomedin; troponin T; unclassified drug; benzhydryl derivative; biological marker; brain natriuretic peptide; empagliflozin; glucoside; insulin-like growth factor binding protein-related protein 1; sodium glucose cotransporter 2 inhibitor; somatomedin binding protein; aged; albumin to creatinine ratio; Article; atrial fibrillation; cardiorenal syndrome; cardiovascular mortality; cardiovascular risk; clinical feature; clinical outcome; confidence interval; diabetes mellitus; dialysis; electrochemiluminesc