The effect of spironolactone in patients with obesity at risk for heart failure: proteomic insights from the HOMAGE trial

Verdonschot, J. A.J. et al. (2022) The effect of spironolactone in patients with obesity at risk for heart failure: proteomic insights from the HOMAGE trial. Journal of Cardiac Failure, 28(5), pp. 778-786. (doi: 10.1016/j.cardfail.2021.12.005) (PMID:34933097)

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Abstract

Background: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. Methods and Results: Protein biomarkers (n = 276) from the Olink Proseek–Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (–14.8 mm Hg 95% confidence interval –18.45 to –11.12) compared with nonobese patients (–3.6 mm Hg 95% confidence interval –7.82 to 0.66). Conclusions: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.

Item Type:Articles
Additional Information:The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement N° 305507 (HOMAGE). S.H.: This manuscript has been possible thanks to the support of the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Ferreira, Mr Joao Pedro and Pellicori, Dr Pierpaolo
Authors: Verdonschot, J. A.J., Ferreira, J. P., Pizard, A., Pellicori, P., Brunner La Rocca, H.-P., Clark, A. L., Cosmi, F., Cuthbert, J., Girerd, N., Waring, O. J., Henkens, M. H.T.M., Mariottoni, B., Petutschnigg, J., Rossignol, P., Hazebroek, M. R., Cleland, J. G.F., Zannad, F., and Heymans, S. R.B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Journal of Cardiac Failure
Publisher:Elsevier
ISSN:1071-9164
ISSN (Online):1532-8414
Published Online:18 December 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Journal of Cardiac Failure 28(5): 778-786
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190666HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507Institute of Cardiovascular & Medical Sciences