Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial

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,...

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Main Authors: Luca Monzo, Masatake Kobayashi, João Pedro Ferreira, Zohra Lamiral, Christian Delles, Andrew L. Clark, Frank Edelmann, Arantxa González, Stephane Heymans, Pierpaolo Pellicori, Johannes Petutschnigg, Job A. J. Verdonschot, Patrick Rossignol, John G. F. Cleland, Faiez Zannad, Nicolas Girerd, on behalf of the HOMAGE “Heart Omics in AGEing” Trial Committees and Investigators
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Cardiovascular Diabetology
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Online Access:https://doi.org/10.1186/s12933-025-02609-8
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author Luca Monzo
Masatake Kobayashi
João Pedro Ferreira
Zohra Lamiral
Christian Delles
Andrew L. Clark
Frank Edelmann
Arantxa González
Stephane Heymans
Pierpaolo Pellicori
Johannes Petutschnigg
Job A. J. Verdonschot
Patrick Rossignol
John G. F. Cleland
Faiez Zannad
Nicolas Girerd
on behalf of the HOMAGE “Heart Omics in AGEing” Trial Committees and Investigators
author_facet Luca Monzo
Masatake Kobayashi
João Pedro Ferreira
Zohra Lamiral
Christian Delles
Andrew L. Clark
Frank Edelmann
Arantxa González
Stephane Heymans
Pierpaolo Pellicori
Johannes Petutschnigg
Job A. J. Verdonschot
Patrick Rossignol
John G. F. Cleland
Faiez Zannad
Nicolas Girerd
on behalf of the HOMAGE “Heart Omics in AGEing” Trial Committees and Investigators
author_sort Luca Monzo
collection DOAJ
description 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. Graphic abstract Summary of the study design and key findings. Abbreviations: CAD, coronary artery disease; DM, diabetes mellitus; LV, left ventricular; M0, baseline; M1, 1-month follow-up; M9, 9-month follow-up; PICP, procollagen type I C-terminal propeptide.
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spelling doaj-art-3d131a5b0c2d4d79ab0e75dcd44fc2492025-08-20T01:57:45ZengBMCCardiovascular Diabetology1475-28402025-03-0124111210.1186/s12933-025-02609-8Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trialLuca Monzo0Masatake Kobayashi1João Pedro Ferreira2Zohra Lamiral3Christian Delles4Andrew L. Clark5Frank Edelmann6Arantxa González7Stephane Heymans8Pierpaolo Pellicori9Johannes Petutschnigg10Job A. J. Verdonschot11Patrick Rossignol12John G. F. Cleland13Faiez Zannad14Nicolas Girerd15on behalf of the HOMAGE “Heart Omics in AGEing” Trial Committees and InvestigatorsCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineSchool of Cardiovascular and Metabolic Health, University of GlasgowDepartment of Cardiology, Castle Hill Hospital, University of HullDeutsches Herzzentrum der Charité, Klinik für Kardiologie, Angiologie & IntensivmedizinDepartment of Pathology, Anatomy and Physiology Universidad de Navarra and IdiSNA, CIMA Universidad de NavarraDepartment of Cardiology, Maastricht University Medical CenterRobertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of GlasgowDeutsches Herzzentrum der Charité, Klinik für Kardiologie, Angiologie & IntensivmedizinDepartment of Cardiology, Maastricht University Medical CenterCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineRobertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, University of GlasgowCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineCentre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de LorraineAbstract 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. Graphic abstract Summary of the study design and key findings. Abbreviations: CAD, coronary artery disease; DM, diabetes mellitus; LV, left ventricular; M0, baseline; M1, 1-month follow-up; M9, 9-month follow-up; PICP, procollagen type I C-terminal propeptide.https://doi.org/10.1186/s12933-025-02609-8Collagen markersEchocardiographyHeart failureDiabetesCoronary artery disease
spellingShingle Luca Monzo
Masatake Kobayashi
João Pedro Ferreira
Zohra Lamiral
Christian Delles
Andrew L. Clark
Frank Edelmann
Arantxa González
Stephane Heymans
Pierpaolo Pellicori
Johannes Petutschnigg
Job A. J. Verdonschot
Patrick Rossignol
John G. F. Cleland
Faiez Zannad
Nicolas Girerd
on behalf of the HOMAGE “Heart Omics in AGEing” Trial Committees and Investigators
Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
Cardiovascular Diabetology
Collagen markers
Echocardiography
Heart failure
Diabetes
Coronary artery disease
title Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
title_full Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
title_fullStr Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
title_full_unstemmed Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
title_short Echocardiographic and biomarker characteristics in diabetes, coronary artery disease or both: insights from HOMAGE trial
title_sort echocardiographic and biomarker characteristics in diabetes coronary artery disease or both insights from homage trial
topic Collagen markers
Echocardiography
Heart failure
Diabetes
Coronary artery disease
url https://doi.org/10.1186/s12933-025-02609-8
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