IGFBP-7 and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF

Adamson, C. et al. (2023) IGFBP-7 and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF. JACC: Heart Failure, 11(3), pp. 291-304. (doi: 10.1016/j.jchf.2022.09.004) (PMID:36592046)

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Background: Insulin-like growth factor–binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown. Objectives: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Methods: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means. Results: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34). Conclusions: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

Item Type:Articles
Glasgow Author(s) Enlighten ID:Adamson, Dr Carly and Docherty, Dr Kieran and Jhund, Professor Pardeep and Sattar, Professor Naveed and Welsh, Professor Paul and McMurray, Professor John and Kober, Professor Lars
Authors: Adamson, C., Welsh, P., Docherty, K. F., de Boer, R. A., Diez, M., Drożdż, J., Dukát, A., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Ljungman, C. E.A., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Morrow, D. A., Lindholm, D., Hammarstedt, A., Boulton, D. W., Greasley, P. J., Langkilde, A. M., Solomon, S. D., Sattar, N., McMurray, J. J.V., and Jhund, P. S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:JACC: Heart Failure
ISSN (Online):2213-1787
Published Online:09 November 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in JACC: Heart Failure 11(3): 291-304
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science