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.
Highlights
Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF)
The Heart OMics in AGEing” (HOMAGE) (Heart OMics in AGEing) trial showed that treatment with spironolactone in patients at risk of developing HF led to a decrease in collagen synthesis markers, N-terminal pro brain natriuretic peptide (NT-proBNP), reduced blood pressure and improved cardiac remodelling [5, 6]
In this pre-specified secondary analysis of the HOMAGE trial, we aimed to (1) compare the clinical characteristics of patients with and without DM; (2) study the biomarker profiles, networks and pathways associated with DM at baseline, as compared to patients without diabetes; (3) to assess the effect of spironolactone on the circulating proteomic biomarkers in patients with DM; and (4) to explore whether the DM status might have modified the effect of spironolactone on the main outcomes assessed in the HOMAGE trial
Summary
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 remodel‐ ling 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. Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF) [1] but the mechanisms are poorly established. The HOMAGE (Heart OMics in AGEing) trial showed that treatment with spironolactone (vs usual care) in patients at risk of developing HF led to a decrease in collagen synthesis markers, N-terminal pro brain natriuretic peptide (NT-proBNP), reduced blood pressure and improved cardiac remodelling [5, 6]. It remains unknown to what extent DM influences the effects of spironolactone on clinical and proteomic variables
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