Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial

Verdonschot, J. A.J. et al. (2021) Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial. Cardiovascular Diabetology, 20, 163. (doi: 10.1186/s12933-021-01357-9)

Abstract

Background: Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The “Heart OMics in AGEing” (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Methods: Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Results: Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Conclusions: Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.

• 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 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., Pellicori, P., Brunner La Rocca, H.-P., Clark, A. L., Cosmi, F., Cuthbert, J., Girerd, N., Mariottoni, B., Petutschnigg, J., Rossignol, P., Cleland, J. G.F., Zannad, F., and Heymans, S. R.B.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Cardiovascular Diabetology
• Publisher: BioMed Central
• ISSN: 1475-2840
• ISSN (Online): 1475-2840
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Cardiovascular Diabetology 20: 163
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190666		HOMAGE: Heart OMics in AGEing	Christian Delles	European Commission (EC)	305507	Institute of Cardiovascular & Medical Sciences