Monzo, Luca and Kobayashi, Masatake and Ferreira, João Pedro and Lamiral, Zohra and Delles, Christian and Clark, Andrew L. and Edelmann, Frank and González, Arantxa and Heymans, Stephane and Pellicori, Pierpaolo and Petutschnigg, Johannes and Verdonschot, Job A. J. and Rossignol, Patrick and Cleland, John and Zannad, Faiez and Girerd, Nicolas (2025) Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial. Cardiovascular Diabetology, 24: 111. ISSN 1475-2840

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Abstract

Background
Coronary artery disease (CAD) and diabetes mellitus (DM) can induce changes in myocardial structure and function, thereby increasing the risk of heart failure (HF). We aimed to identify the alterations in echocardiographic variables and circulating biomarkers associated with DM, CAD, or both and to assess the effect of spironolactone on them.

Methods
The “Heart OMics in AGEing” (HOMAGE) trial evaluated the effect of spironolactone on circulating markers of fibrosis over 9 months of follow-up in people at risk for HF. From the initial population (N = 527) of the HOMAGE trial, a total of 495 participants (mean age 74 years, 25% women) were categorized according to clinical phenotype (DM-/CAD + vs. DM+/CAD- vs. DM+/CAD+), while the DM-/CAD- group was excluded due to the low sample size (N = 32). Multivariable linear regression analysis was used to assess the relations between variables and DM/CAD status.

Results
At baseline, participants with DM, whether or not they had CAD, showed lower markers of type I collagen synthesis (procollagen type I C-terminal propeptide; β [95% CI]: DM+/CAD-: -6.973 [-13.778; -0.167]; DM+/CAD+: -9.039 [-15.174; -2.903]), reduced left ventricular volumes (β [95% CI]: end-diastolic, DM+/CAD-: -6.323 [-9.696; -2.951]; DM+/CAD+: -2.503 [-5.531; 0.526]; end-systolic, DM+/CAD-: -2.905 [-4.817; -0.992]; DM+/CAD+: -1.400 [-3.120; 0.320]) and higher levels of galectin-3 (Exponential β [95% CI]: DM+/CAD-: 1.127 [1.050; 1.209]; DM+/CAD+: 1.118 [1.048; 1.192]), and growth differentiation factor-15 (Exponential β [95% CI]: DM+/CAD-: 1.542 [1.360; 1.747]; DM+/CAD+: 1.535 [1.370; 1.720]), along with an elevated E/e’ ratio (β [95% CI]: DM+/CAD-: 1.355 [0.462; 2.248]; DM+/CAD+: 0.879 [0.067; 1.690]), compared with DM-/CAD + individuals (all p &lt; 0.05). At follow-up, the effect of spironolactone on echocardiographic variables and circulating biomarkers was not significantly different across DM/CAD phenotypes (all p-interaction &gt; 0.05), except for a more pronounced reduction in GDF-15 in the DM+/CAD + group at the 1-month visit (p-interaction = 0.03).

Conclusions
Among HOMAGE trial participants, diabetes was a powerful driver of biomarker and echocardiographic alterations irrespectively of CAD. These alterations were mainly related to the domains of inflammation and diastolic function.

Information
Title Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
Creators Monzo, Luca and Kobayashi, Masatake and Ferreira, João Pedro and Lamiral, Zohra and Delles, Christian and Clark, Andrew L. and Edelmann, Frank and González, Arantxa and Heymans, Stephane and Pellicori, Pierpaolo and Petutschnigg, Johannes and Verdonschot, Job A. J. and Rossignol, Patrick and Cleland, John and Zannad, Faiez and Girerd, Nicolas
Identification Number 10.1186/s12933-025-02609-8
Date 8 March 2025
Divisions College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Publisher BioMed Central
Additional Information The research leading to these results has received funding from the European Union Commission’s Seventh Framework programme under Grant Agreement No. 305507 (HOMAGE). Consortia: HOMAGE “Heart Omics in AGEing” Trial Committees and Investigators.
Library
URI https://pub.demo35.eprints-hosting.org/id/eprint/39
Item Type Article
Depositing User Unnamed user with email ejo1f20@soton.ac.uk
Date Deposited 11 Jun 2025 16:34
Revision 40
Last Modified 11 Jun 2025 16:34
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