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

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 < 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 > 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.

People
Monzo, Luca
Author

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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Kobayashi, Masatake
Author

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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Ferreira, João Pedro
Author

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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Lamiral, Zohra
Author

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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Delles, Christian
Author

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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Clark, Andrew L.
Author

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

Cleland, John and Pellicori, Pierpaolo and Graham, Fraser J. and Lane, Rebecca and Petrie, Mark C. and Ahmed, Fozia and Squire, Iain B. and Ludman, Andrew and Japp, Alan and Al-Mohammad, Abdallah and Clark, Andrew L. and Szwejkowski, Ben and Critoph, Chris and Chong, Victor and Schiff, Rebekah and Nageh, Thuraia and Glover, Jason and McMurray, John J.V. and Thomson, Elizabeth A. and Robertson, Michele and Ford, Ian and Kalra, Philip A. and Kalra, Paul R. (2024) Adjudication of hospitalizations and deaths in the IRONMAN Trial of intravenous iron for heart failure. Journal of the American College of Cardiology, 84 (18). pp. 1704-1717. ISSN 0735-1097

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Edelmann, Frank
Author

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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González, Arantxa
Author

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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Heymans, Stephane
Author

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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Pellicori, Pierpaolo
Author

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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Petutschnigg, Johannes
Author

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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Verdonschot, Job A. J.
Author

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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Rossignol, Patrick
Author

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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Cleland, John
Author

Taylor, Rod and Burrell, Emma and O’Hare, Claire and Thomson, Elizabeth and Placzek, Anna and Bollen, Jessica and Cleland, John G.F. and Cowie, Ansley and Dalal, Hasnain and Deaton, Christi and Doherty, Patrick and Dudman, Katie and Fraser, Heather and Frost, Julia and Greaves, Colin J. and Hartshorne-Evans, Nick and Hillsdon, Melvyn and Ibbotson, Tracy and Jarallah, Mohammad and Jolly, Kate and McConnachie, Alex and McIntosh, Emma and Smith, Valerie and Squire, Iain and Taylor, Louise and van Beurden, Sam and Lang, Chim C. and REACH-HFpEF investigators (2025) Clinical effectiveness and cost-effectiveness of the rehabilitation enablement in chronic heart failure facilitated self-care rehabilitation intervention for people with heart failure with preserved ejection fraction and their caregivers: rationale and protocol for a multicentre randomised controlled trial – REACH-HFpEF trial. BMJ Open, 15 (5): e094254. ISSN 2044-6055

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

Cleland, John and Pellicori, Pierpaolo and Graham, Fraser J. and Lane, Rebecca and Petrie, Mark C. and Ahmed, Fozia and Squire, Iain B. and Ludman, Andrew and Japp, Alan and Al-Mohammad, Abdallah and Clark, Andrew L. and Szwejkowski, Ben and Critoph, Chris and Chong, Victor and Schiff, Rebekah and Nageh, Thuraia and Glover, Jason and McMurray, John J.V. and Thomson, Elizabeth A. and Robertson, Michele and Ford, Ian and Kalra, Philip A. and Kalra, Paul R. (2024) Adjudication of hospitalizations and deaths in the IRONMAN Trial of intravenous iron for heart failure. Journal of the American College of Cardiology, 84 (18). pp. 1704-1717. ISSN 0735-1097

See full publications list
Zannad, Faiez
Author

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

See full publications list
Girerd, Nicolas
Author

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

See full publications list
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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.
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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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