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

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.

• Authors: Job A J Verdonschot, João Pedro Ferreira, Pierpaolo Pellicori, Hans-Peter Brunner-La Rocca, Andrew L Clark, Franco Cosmi, Joe Cuthbert, Nicolas Girerd, Beatrice Mariottoni, Johannes Petutschnigg, Patrick Rossignol, John G F Cleland, Faiez Zannad, Stephane R B Heymans, HOMAGE “Heart Omics in AGEing” consortium
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 20 Issue 1 Pg. 163 (08 09 2021) ISSN: 1475-2840 [Electronic] England
• PMID: 34372849 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Biomarkers
• Blood Proteins
• Mineralocorticoid Receptor Antagonists
• Proteome
• Spironolactone

Topics

• Aged
• Biomarkers (blood)
• Blood Proteins (analysis)
• Diabetes Mellitus (blood, diagnosis, drug therapy)
• Diabetic Cardiomyopathies (blood, diagnosis, drug therapy)
• Female
• Heart Failure (blood, diagnosis, drug therapy)
• Humans
• Male
• Mineralocorticoid Receptor Antagonists (therapeutic use)
• Predictive Value of Tests
• Prospective Studies
• Proteome
• Proteomics
• Risk Assessment
• Risk Factors
• Spironolactone (therapeutic use)
• Time Factors
• Treatment Outcome