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

Authors
  • Verdonschot, Job A. J.1
  • Ferreira, João Pedro2
  • Pellicori, Pierpaolo3
  • Brunner-La Rocca, Hans-Peter4
  • Clark, Andrew L.5
  • Cosmi, Franco6
  • Cuthbert, Joe5
  • Girerd, Nicolas2
  • Mariottoni, Beatrice6
  • Petutschnigg, Johannes7
  • Rossignol, Patrick2
  • Cleland, John G. F.3
  • Zannad, Faiez2
  • Heymans, Stephane R. B.4
  • 1 Maastricht University Medical Center, Maastricht, The Netherlands , Maastricht (Netherlands)
  • 2 Centre d’Investigations Cliniques Plurithématique 1433, Université de Lorraine, Institut National de la Santé et de la Recherche Médicale 1116, Centre Hospitalier Régional Universitaire de Nancy, French Clinical Research Infrastructure Network, Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Nancy, France , Nancy (France)
  • 3 University of Glasgow, Glasgow Royal Infirmary, Glasgow, G12 8QQ, UK , Glasgow (United Kingdom)
  • 4 Maastricht University Medical Center (MUMC+), Maastricht, 6202 AZ, The Netherlands , Maastricht (Netherlands)
  • 5 University of Hull, Castle Hill Hospital, Cottingham, East Riding of Yorkshire, UK , East Riding of Yorkshire (United Kingdom)
  • 6 Cortona Hospital, Arezzo, Italy , Arezzo (Italy)
  • 7 Campus Virchow Klinikum, Charite´ University Medicine Berlin, Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK), Partner Site Berlin, Berlin, Germany , Berlin (Germany)
Type
Published Article
Journal
Cardiovascular Diabetology
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Aug 09, 2021
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12933-021-01357-9
Source
Springer Nature
Keywords
Disciplines
  • NCT
License
Green

Abstract

BackgroundPatients 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.MethodsProtein 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.ResultsTwenty-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).ConclusionsAmongst 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.

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