Journal
CARDIOVASCULAR DIABETOLOGY
Volume 20, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s12933-021-01357-9
Keywords
Diabetes; Biomarker; Heart failure; Spironolactone; Fibrosis
Funding
- European Union Commission's Seventh Framework programme [305507]
- Netherlands Cardiovascular Research Initiative
- Dutch Heart Foundation [2015-10, 2017-21]
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Among patients at risk for heart failure, diabetic individuals have higher levels of proteins related to inflammation and proteolysis in their plasma compared to non-diabetic patients. Treatment with spironolactone has similar effects on protein biomarkers in diabetic and non-diabetic patients, producing anti-fibrotic, anti-remodelling, blood pressure, and natriuretic peptide lowering effects regardless of diabetes status.
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 (R) 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.
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