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12 results on '"European Project: 305507"'

1. Dyskalemia in people at increased risk for heart failure

Author

Luca Monzo, João Pedro Ferreira, John G.F. Cleland, Pierpaolo Pellicori, Beatrice Mariottoni, Job A.J. Verdonschot, Mark R. Hazebroek, Tim J. Collier, Joe J. Cuthbert, Burkert Pieske, Frank Edelmann, Johannes Petutschnigg, Javed Khan, Fozia Z. Ahmed, Nicolas Girerd, Erwan Bozec, Javier Díez, Arantxa González, Andrew L. Clark, Franco Cosmi, Jan A. Staessen, Stephane Heymans, Patrick Rossignol, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universidade do Porto = University of Porto, University of Glasgow, Department of Cardiology, Cortona Hospital, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], London School of Hygiene and Tropical Medicine (LSHTM), Castle Hill Hospital, University of Hull [United Kingdom], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Manchester University NHS Foundation Trust (MFT), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester], Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Department of Cardiovascular Sciences [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The Netherlands Heart Institute, European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Hyperkalaemia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, heart failure prevention, hyperkalaemia, hypokalaemia, steroidal mineralocorticoid receptor antagonist, Heart failure prevention, Cardiology and Cardiovascular Medicine, Hypokalaemia, Steroidal mineralocorticoid receptor antagonist, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

AIMS: In people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia. METHODS AND RESULTS: The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at 5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration

Published
2022

2. Spironolactone effect on cardiac structure and function of patients with heart failure and preserved ejection fraction: a pooled analysis of three randomized trials

Author

João Pedro Ferreira, John G. Cleland, Nicolas Girerd, Erwan Bozec, Patrick Rossignol, Pierpaolo Pellicori, Franco Cosmi, Beatrice Mariottoni, Scott D. Solomon, Bertram Pitt, Marc A. Pfeffer, Amil M. Shah, Johannes Petutschnigg, Burkert Pieske, Frank Edelmann, Faiez Zannad, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, University of Glasgow, Cortona Hospital, Brigham and Women's Hospital [Boston], University of Michigan [Ann Arbor], University of Michigan System, Charité Campus Virchow-Klinikum (CVK), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), and European Project: 305507

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiology and Cardiovascular Medicine
Abstract

International audience; Aims: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF.Methods and results: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF. Analysis of covariance was used to test the effect of spironolactone on echocardiographic changes. A total of 984 patients were included in this analysis: 452 (45.9%) from HOMAGE, 398 (40.4%) from Aldo-DHF, and 134 (13.6%) from TOPCAT. The pooled-cohort patient's median age was 71 (66-77) years and 39% were women. Median LAVi was 29 (24-35) ml/m2 , LVMi 100 (84-118) g/m2 , IVS thickness 12 (10-13) mm, E/e' ratio 11 (9-13), and LVEF 64 (59-69)%. Spironolactone reduced LAVi by -1.1 (-2.0 to -0.1) ml/m2 (p = 0.03); LVMi by -3.6 (-6.4 to -0.8) g/m2 (p = 0.01); IVS thickness by -0.2 (-0.3 to -0.1) mm (p = 0.01); E/e' ratio by -1.3 (-2.4 to -0.2) (p = 0.02); and increased LVEF by 1.7 (0.8-2.6)% (p < 0.01). No treatment-by-study heterogeneity was found except for E/e' ratio with a larger effect in Aldo-DHF and TOPCAT (interaction p < 0.01).Conclusions: Spironolactone improved cardiac structure and function of patients with HFpEF.

Published
2022

3. Comparison of Proteomic Measurements Across Platforms in the Atherosclerosis Risk in Communities (ARIC) Study

Author

Mary R Rooney, Jingsha Chen, Christie M Ballantyne, Ron C Hoogeveen, Olive Tang, Morgan E Grams, Adrienne Tin, Chiadi E Ndumele, Faiez Zannad, David J Couper, Weihong Tang, Elizabeth Selvin, Josef Coresh, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Baylor College of Medicine (BCM), Baylor University, University of Mississippi Medical Center (UMMC), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, 75N92022D00005). Research reported in this publication was supported by the NIH/NHLBI grants T32HL007024 (Rooney), K24HL152440 (Selvin), R01-HL134320 (Ballantyne and Selvin), R01-HL146907 (Ndumele), NIH/NIDDK grant R01DK089174 (Selvin), and the American Heart Association grant 20SFRN35120152. The research leading to these results has received funding from the European Union Commission’s Seventh Framework Programme under grant agreement No. 305507 (HOMAGE [Heart Omics in Ageing consortium])., European Project: 305507, BOZEC, Erwan, and HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING

Subjects
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Biochemistry (medical), Clinical Biochemistry, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

Background The plasma proteome can be quantified using different types of highly multiplexed technologies, including aptamer-based and proximity-extension immunoassay methods. There has been limited characterization of how these protein measurements correlate across platforms and with absolute measures from targeted immunoassays. Methods We assessed the comparability of (a) highly multiplexed aptamer-based (SomaScan v4; Somalogic) and proximity-extension immunoassay (OLINK Proseek® v5003; Olink) methods in 427 Atherosclerosis Risk in Communities (ARIC) Study participants (Visit 5, 2011–2013), and (b) 18 of the SomaScan protein measurements against targeted immunoassays in 110 participants (55 cardiovascular disease cases, 55 controls). We calculated Spearman correlations (r) between the different measurements and compared associations with case-control status. Results There were 417 protein comparisons (366 unique proteins) between the SomaScan and Olink platforms. The average correlation was r = 0.46 (range: −0.21 to 0.97; 79 [19%] with r ≥ 0.8). For the comparison of SomaScan and targeted immunoassays, 6 of 18 assays (growth differentiation factor 15 [GDF15], interleukin-1 receptor-like 1 [ST2], interstitial collagenase [MMP1], adiponectin, leptin, and resistin) had good correlations (r ≥ 0.8), 2 had modest correlations (0.5 ≤ r < 0.8; osteopontin and interleukin-6 [IL6]), and 10 were poorly correlated (r < 0.5; metalloproteinase inhibitor 1 [TIMP1], stromelysin-1 [MMP3], matrilysin [MMP7], C-C motif chemokine 2 [MCP1], interleukin-10 [IL10], vascular cell adhesion protein 1 [VCAM1], intercellular adhesion molecule 1 [ICAM1], interleukin-18 [IL18], tumor necrosis factor [TNFα], and visfatin) overall. Correlations for SomaScan and targeted immunoassays were similar according to case status. Conclusions There is variation in the quantitative measurements for many proteins across aptamer-based and proximity-extension immunoassays (approximately 1/2 showing good or modest correlation and approximately 1/2 poor correlation) and also for correlations of these highly multiplexed technologies with targeted immunoassays. Design and interpretation of protein quantification studies should be informed by the variation across measurement techniques for each protein.

Published
2023

4. Identification of sex‐specific biomarkers predicting new‐onset heart failure

Author

Anne G. Raafs, Christian Delles, Andrew L. Clark, Arantxa González, Nicolas Vodovar, Timothy Collier, Michiel T H M Henkens, Jan A. Staessen, Javier Díez, Alessandro Boccanelli, João Pedro Ferreira, Florence Pinet, Ping Wang, Patrick Rossignol, Mark R. Hazebroek, Vanessa P. M. van Empel, John G.F. Cleland, Faiez Zannad, J. Wouter Jukema, Rudolf A. de Boer, Jens Björkman, Nicolas Girerd, Thomas Thum, Stephane Heymans, Job Verdonschot, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Cardiovascular Research Institute Maastricht (CARIM), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), London School of Hygiene and Tropical Medicine (LSHTM), TATAA Biocenter AB, Casa di Cura Quisisana, University of Hull [United Kingdom], Castle Hill Hospital, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, CIBERCV, Carlos III Institute of Health, Instituto de Investigacion Sanitaria de Navarra (IdiSNA), Universidad de Navarra [Pamplona] (UNAV), Clínica Universidad de Navarra [Pamplona], Netherlands Heart Institute, Partenaires INRAE, Leiden University Medical Center (LUMC), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Fraunhofer (Fraunhofer-Gesellschaft), Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, University Medical Center Groningen [Groningen] (UMCG), Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing, Royal Brompton and Harefield NHS Foundation Trust, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, The research leading to these results has received funding from the European Union Commission's Seventh Framework Programme under grant agreement 305507 [HOMAGE (Heart Omics in Ageing consortium)]. We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with the support of the Dutch Heart Foundation CVON2016-Early HFPEF, and CVON 2017-21, SHE-PREDICTS-HF. JPF, NG, PR, and FZ are supported by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d'Avenir' programme FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d'Excellence', reference ANR-15-IDEX-04-LUE. They thank the CRB lorrain for biobaking activities. JAS is supported by the Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine (URL: http://www.appremed.org), Mechelen, Belgium received a non-binding research grant from OMRON Healthcare Co., Ltd., Kyoto, Japan., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), European Project: 305507, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universiteit Leiden, Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Cardiologie, RS: Carim - H02 Cardiomyopathy, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: MA Med Staf Spec Cardiologie (9), MUMC+: MA Med Staf Artsass Cardiologie (9), Cardiovascular Centre (CVC), BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, and Publica

Subjects
Male, Proteomics, Cardiac & Cardiovascular Systems, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, DESIGN, Original Research Articles, Medicine, Original Research Article, 030212 general & internal medicine, ASSOCIATIONS, RISK, Sex Characteristics, WOMEN, Pathophysiology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cohort, Biomarker (medicine), Female, ADIPOSITY, HORMONES, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, Incident heart failure, New onset, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Sex differences, Humans, Diseases of the circulatory (Cardiovascular) system, ANTAGONIST, Heart Failure, Science & Technology, business.industry, INTERLEUKIN-17, medicine.disease, GENE, Interleukin 1 receptor antagonist, Case-Control Studies, Heart failure, RC666-701, Cardiovascular System & Cardiology, IL17A, business, Biomarkers
Abstract

AIMS: Heart failure (HF) is common in both men and women, yet disease pathophysiology, presentation, and progression differ between sexes. Studies addressing whether biomarkers predict new onset HF sex-specifically are scarce. This study therefore aims to test the sex-specificity of 252 protein biomarkers for new-onset HF. METHODS AND RESULTS: A matched case-control design in patients selected from cohorts within the HOMAGE consortium was used. Cases (new-onset HF, n = 562) and controls (n = 780) were matched for cohort (PREDICTOR, HEALTH-ABC, & PROSPER), follow-up time (defined as time from entry to incident HF), and age. Incident HF was defined as first hospitalization for HF. Targeted plasma proteins (n = 252) were measured using Proximity Extension Assay technology from O-link. To look for sex differences for new onset HF, we adjusted for cohort, age, and baseline clinical parameters. At baseline, women had a biomarker profile reflecting activated metabolism and immune responses. However, none of the biomarkers had a significant interaction with sex in predicting new onset HF, but four biomarkers had a trend towards sex-specificity (P

Published
2021

5. Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery

Author

Kristjan Karason, Nicolas Girerd, Johanna Andersson-Asssarsson, Kevin Duarte, Magdalena Taube, Per-Arne Svensson, Anne-Cecile Huby, Markku Peltonen, Lena M. Carlsson, Faiez Zannad, Sahlgrenska Academy at University of Gothenburg [Göteborg], Sahlgrenska University Hospital [Gothenburg], Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), National Institute for Health and Welfare [Helsinki], European Union Commission Seventh Framework Program under grant agreement (No. 305507), the Swedish federal government under the ALF agreement (ALFGBG-633141, 775351, 725971, 717881, 932636), Swedish Research Council (2017-01707), The Swedish Heart-Lung Foundation (20180410) and the Novo Nordisk Foundation (NNF 19OC0057184). Open access funding provided by University of Gothenburg., European Project: 305507, BOZEC, Erwan, and HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING

Subjects
Proteomics, Heart Failure, Inflammation, Nutrition and Dietetics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Endocrinology, Diabetes and Metabolism, Case-Control Studies, Medicine (miscellaneous), Humans, Obesity, Biomarkers, Hormones, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract

Background Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. Methods We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. Results A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] Conclusion Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

Published
2022

6. The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial

Author

Job A.J. Verdonschot, JoÃo Pedro Ferreira, Anne Pizard, Pierpaolo Pellicori, Hans-Peter Brunner La Rocca, Andrew L. Clark, Franco Cosmi, Joe Cuthbert, Nicolas Girerd, Olivia J. Waring, Michiel H.T.M. Henkens, Beatrice Mariottoni, Johannes Petutschnigg, Patrick Rossignol, Mark R. Hazebroek, John G.F. Cleland, Faiez Zannad, Stephane R.B. Heymans, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, University of Hull [United Kingdom], Cortona Hospital, Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement N° 305507 (HOMAGE). S.H.: This manuscript has been possible thanks to the support of the the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, MUMC+: MA Med Staf Artsass Cardiologie (9), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and Department of Cardiology, Cortona Hospital

Subjects
Male, Proteomics, obesity, Cardiac & Cardiovascular Systems, heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, LEPTIN, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PEOPLE, Glucose Intolerance, Humans, Obesity, 030304 developmental biology, Mineralocorticoid Receptor Antagonists, 0303 health sciences, INSULIN-RESISTANCE, Science & Technology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, spironolactone, ADRENOMEDULLIN, FAT, Cardiovascular System & Cardiology, biomarker, Female, ADIPOKINE, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Biomarkers
Abstract

BACKGROUND: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone. METHODS AND RESULTS: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (Pinteraction = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66). CONCLUSIONS: Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure. ispartof: JOURNAL OF CARDIAC FAILURE vol:28 issue:5 pages:778-786 ispartof: location:United States status: published

Published
2022

7. Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20‐Year Follow‐Up

Author

Mehmet Kanbay, Constance Xhaard, Edith Le Floch, Claire Dandine‐Roulland, Nicolas Girerd, João Pedro Ferreira, Jean‐Marc Boivin, Sandra Wagner, Delphine Bacq‐Daian, Jean‐François Deleuze, Faiez Zannad, Patrick Rossignol, Koç University, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), The STANISLAS (Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux) study is sponsored by the Nancy Centre Hospitalier Régional Universitaire. This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat‐Lorraine and Fonds Européen de Développement Régional Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT‐heart failure (reference: ANR‐15‐RHU‐0004) and by the French Plan d'Investissement d'Avenir project 'Lorraine Université d’Excellence,' reference ANR‐15‐IDEX‐04‐LUE. It is also supported by the European Fibro‐Targets Project (grant agreement No. SP7#602904), European HOMAGE project (grant agreement No. Heart 'Omics' in Ageing, 7th Framework Program grant No. 305507), the MEDIA project (Européen 'Cooperation'–Theme 'Health'/FP7‐HEALTH‐2010‐single‐stage (reference: 261409), FOCUS‐MR (reference: ANR‐15‐CE14‐0032‐01), ERA‐CVD EXPERT (reference: ANR‐16‐ECVD‐0002‐02), and the Fondation de Recherche en Hypertension Artérielle., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project: SP7#602904, European Project: 305507, European Project: 261409,EU FP 7 MEDIA project, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque - - MR-focus2015 - ANR-15-CE14-0032 - AAPG2015 - VALID, Exploring new pathways in age-related heart diseases - - EXPERT2016 - ANR-16-ECVD-0002 - ERA-CVD - VALID, European Fibro‐Targets Project - SP7#602904 - INCOMING, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, The MEtabolic Road to DIAstolic Heart Failure - EU FP 7 MEDIA project - 261409 - INCOMING, Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Xhaard, C., Le Floch, E., Dandine-Roulland, C., Girerd, N., Ferreira, J.P., Boivin, J.M., Wagner, S., Bacq Daian, D., Deleuze, J.F., Zannad, F., Rossignol, P., and School of Medicine

Subjects
Genetic Markers, Glucose Transport Proteins, Facilitative, Hyperuricemia, Cardiovascular system and cardiology, Blood Pressure Monitoring, Ambulatory, Pulse Wave Analysis, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Uric Acid, Cardiovascular disease, Genome-wide, Association study, Single-nucleotide Polymorphism, Uric acid, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Humans, Cardiology and Cardiovascular Medicine, Follow-Up Studies, Genome-Wide Association Study
Abstract

Background: Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and results: the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Sante des Lorrains Assures Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed approximate to 20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima-media thickness. Conclusions: our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease., Nancy Centre Hospitalier Regional Universitaire; French Ministry of Health; French National Research Agency (ANR); Contrat de Plan Etat?Lorraine and Fonds Européen de Développement Régional Lorraine; Programme Hospitalier de Recherche Clinique Inter regional 2013; Investissements d’Avenir; FIGHT?heart failure; French Plan d'Investissement d'Avenir project “Lorraine Université d’Excellence; European Union (EU); European Fibro?Targets Project; European HOMAGE project; 7th Framework Program; MEDIA project; FOCUS?MR; ERA?CVD EXPERT; Fondation de Recherche en Hypertension Artérielle

Published
2022

8. Comparing and contrasting risk factors for heart failure in patients with and without history of myocardial infarction

Author

Tripti Rastogi, Frederick K. Ho, Patrick Rossignol, Thomas Merkling, Javed Butler, Andrew Clark, Timothy Collier, Christian Delles, J Wouter Jukema, Stephane Heymans, Roberto Latini, Alexandre Mebazaa, Pierpaolo Pellicori, Peter Sever, Jan A. Staessen, Lutgarde Thijs, John G. Cleland, Naveed Sattar, Faiez Zannad, Nicolas Girerd, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, Mississippi State University [Mississippi], University of Hull [United Kingdom], London School of Hygiene and Tropical Medicine (LSHTM), Leiden University Medical Center (LUMC), Universiteit Leiden, Netherlands Heart Institute, Partenaires INRAE, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Department of Cardiovascular Sciences [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Imperial College London, Research Institute Alliance for the Promotion of Preventive Medicine (APPREMED), The research leading to these results has received funding from the European Union Commission’s Seventh Framework Programme under grant agreement No. 305507 (HOMAGE [Heart Omics in Ageing consortium]). UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, and Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine)

Subjects
Male, Survival, PREDICTION, heart failure, Heart failure, survival, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Diabetes Mellitus, Humans, Biological Specimen Banks, BORDERLINE, HYPERTENSION, MORTALITY, PULSE PRESSURE, EFFICACY, United Kingdom, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiovascular diseases, Myocardial infarction, myocardial infarction, Cardiovascular diseases, Cardiology and Cardiovascular Medicine, AGING HOMAGE, REDUCED EJECTION FRACTION, SYSTOLIC BLOOD-PRESSURE
Abstract

AIMS: Myocardial infarction (MI) is among the commonest attributable risk factors for heart failure (HF). We compared clinical characteristics associated with the progression to HF in patients with or without a history of MI in the HOMAGE cohort and validated our results in UK Biobank. METHODS AND RESULTS: During a follow-up of 5.2 (3.5-5.9) years, 177 (2.4%) patients with prior MI and 370 (1.92%) patients without prior MI experienced HF onset in the HOMAGE cohort (n = 26 478, history of MI: n = 7241). Older age, male sex and higher heart rate were significant risk factors of HF onset in patients with and without prior MI. Lower renal function was more strongly associated with HF onset in patients with prior MI. Higher body mass index (BMI), systolic blood pressure and blood glucose were significantly associated with HF onset only in patients without prior MI (all p for interactions

Published
2022

9. Quality of Beverage Intake and Cardiometabolic and Kidney Outcomes: Insights From the STANISLAS Cohort

Author

Sandra Wagner, Thomas Merkling, Nicolas Girerd, Erwan Bozec, Laurie Van den Berghe, Axelle Hoge, Michèle Guillaume, Mehmet Kanbay, Céline Cakir-Kiefer, Simon N. Thornton, Jean-Marc Boivin, Ludovic Mercklé, Martine Laville, Patrick Rossignol, Julie-Anne Nazare, Kanbay, Mehmet (ORCID 0000-0002-1297-0675 & YÖK ID 110580), Wagner, S., Merkling, T., Girerd, N., Bozec, E., Van den Berghe, L., Hoge, A., Guillaume, M., Cakir Kiefer, C., Thornton, S.N., Boivin, J.M., Merckle, L., Laville, M., Rossignol, P., Nazare J.A., School of Medicine, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Liège, Koç University, Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The fourth examination of the STANISLAS study was sponsored by the Centre Hospitalier Régional Universitaire of Nancy (CHRU) and supported by the French Ministry of Health (Programme Hospitalier de Recherche Clinique Inter-régional 2013), the Contrat de Plan Etat-Lorraine IT2MP and the Fonds Européen de Développement Régional (FEDER Lorraine), a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d'Avenir program FIGHT-HF (reference: ANR-15-RHU-0004), and the French Projet investissement d'avenir (PIA) project Lorraine Université d'Excellence (reference ANR-15-IDEX-04-LUE). The STANISLAS study is also supported by the sixth European Union—Framework Program (EU-FP) Network of Excellence Ingenious HyperCare (#LSHM-CT-2006–037093), the seventh EU-FP MEDIA (Européen Cooperation—Theme Health/FP7-HEALTH-2010-single-stage #261409), HOMAGE (Heart Omics in Aging, 7th Framework Program grant #305507), FOCUS-MR (reference: ANR-15-CE14-0032-01), and FIBRO-TARGETS (FP7#602904) projects, and by ERA-CVD EXPERT (reference: ANR-16-ECVD-0002-02)., ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-CE14-0032,MR-focus,Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque(2015), ANR-16-ECVD-0002,EXPERT,Exploring new pathways in age-related heart diseases(2016), European Project: #LSHM-CT-2006–037093, European Project: 602904,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,FIBRO-TARGETS(2013), European Project: 261409,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MEDIA(2011), European Project: 305507, BOZEC, Erwan, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Régulation, Diagnostique et Thérapeutique ciblée du récepteur minéralocorticoïde dans le remodelage cardiaque - - MR-focus2015 - ANR-15-CE14-0032 - AAPG2015 - VALID, Exploring new pathways in age-related heart diseases - - EXPERT2016 - ANR-16-ECVD-0002 - ERA-CVD - VALID, sixth European union – framework program (EU-FP) Network of Excellence Ingenious HyperCare (#LSHM-CT-2006–037093) - #LSHM-CT-2006–037093 - INCOMING, Targeting cardiac fibrosis for heart failure treatment - FIBRO-TARGETS - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 602904 - VALID, The MEtabolic Road to DIAstolic Heart Failure - MEDIA - - EC:FP7:HEALTH2011-01-01 - 2016-06-30 - 261409 - VALID, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)

Subjects
2. Zero hunger, metabolic health, beverages, Nutrition and Dietetics, Nutrition. Foods and food supply, Endocrinology, Diabetes and Metabolism, Healthy Beverage Index, adult consumption, cardiovascular health, 030204 cardiovascular system & hematology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Nutrition and dietetics, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, parasitic diseases, TX341-641, 030212 general & internal medicine, kidney function, Nutrition, Original Research, Adult consumption, Beverages, Cardiovascular health, Healthy beverage index, Kidney function, Metabolic health, Food Science
Abstract

Background and aims: beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort. Methods: this study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models. Results: the median HBI score was 89.7 (78.6–95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria (p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the “low Fat milk” (p = 0.06) and “alcohol” (p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria (p < 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria (p = 0.047). Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health., Centre Hospitalier Regional Universitaire of Nancy (CHRU); French Ministry of Health (Programme Hospitalier de Recherche Clinique Inter-regional 2013); Fonds Europeen de Developpement Regional (FEDER Lorraine); French National Research Agency (ANR); European Union (EU); Horizon 2020; 6th EU Research Framework Programme Network of Excellence Ingenious HyperCare; 7th Research Framework Programme Europeen Cooperation-Theme Health/FP7HEALTH-2010-single-stage; Heart OMics in AGEing (HOMEGA); FOCUS-MR; FIBROTARGETS; ERA-CVD EXPERT; Contrat de Plan Etat-Lorraine IT2MP

Published
2022
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10. Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial

Author

Andrew L. Clark, Javier Díez, Pierpaolo Pellicori, Investigators, Nicolas Girerd, Job A J Verdonschot, João Pedro Ferreira, Susana Ravassa, Frank Edelmann, Stephane Heymans, Beatrice Mariottoni, María U. Moreno, Homage Trial Committees, Franco Cosmi, Jan A. Staessen, Burkert Pieske, John G.F. Cleland, Faiez Zannad, Johannes Petutschnigg, Mark R. Hazebroek, Joe Cuthbert, Arantxa González, Begoña López, Erwan Bozec, Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain, CIBERCV, Carlos III Institute of Health, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow Royal Infirmary, Department of Cardiology, Cortona Hospital, Department of Cardiology, Maastricht University Medical Center, Cardiology Department, Castle Hill Hospital, University of Hull, Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, and German Centre for Cardiovascular research (DZHK), Partner Site Berlin, Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen (APPREMED), Biomedical Sciences Group, Faculty of Medicine, University of Leuven, Berlin Institute of Health (BIH), Departments of Nephrology and Cardiology, Clínica Universidad de Navarra, This work was supported by the European Commission HOMAGE project (grant 305507), JD and AG are supported by the Ministry of Science and Innovation, Spain (Instituto de Salud Carlos III: CB16/11/00483 and PI18/01469 co-financed by FEDER funds). MH is supported by a Kootstra Talented Post-doc Fellowship (Netherlands). JGFC and PP are supported by the British Heart Foundation Centre of Research Excellence (grant number RE/18/6/34217). PPREMED (URL: http://www.appremed.orf) received a non-binding grant from Omron Healthcare Co., Ltd., Kyoto, Japan., European Project: 305507, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, MUMC+: MA Med Staf Artsass Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Cardiac function curve, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Heart failure, 030204 cardiovascular system & hematology, Spironolactone, EXERCISE CAPACITY, Atrial remodelling, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, N-terminal telopeptide, Left atrial, Collagen cross-linking, Internal medicine, MAGNETIC-RESONANCE, medicine, FIBROSIS, 030212 general & internal medicine, Science & Technology, Ejection fraction, business.industry, medicine.disease, DYSFUNCTION, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, PRESERVED EJECTION FRACTION, chemistry, VOLUME, Cardiovascular System & Cardiology, SURVIVAL, Cardiology, Biomarker (medicine), FIBRILLATION, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Blood sampling
Abstract

Aims The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial.Methods and results Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean difference(sspiro/control): -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m(2); interaction p(across-tertiles) = 0.005; interaction p(third tertile) = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differences(spiro/control): -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction p(across-tertiles) = 0.09; interaction p(third tertile) < 0.001].Conclusions These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).[GRAPHICS]Patients at risk of heart failure from the HOMAGE clinical trial were classified according to the baseline degree of myocardial collagen cross-linking, non-invasively assessed by the serum collagen type I C-terminal telopeptide (CITP) to matrix metalloproteinase-1 (MMP-1) ratio (CITP:MMP-1). As highly cross-linked collagen fibres are more resistant to degradation and CITP is a cross-linked peptide, for a given MMP-1 quantity less CITP will be released and, subsequently, serum CITP:MMP-1 will be lower. Whereas patients with low collagen cross-linking (high CITP:MMP-1) benefit from the cardioprotective effects of treatment with spironolactone on left atrial remodelling [i.e. a decrease in left atrial volume index (LAVI)] and on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, these beneficial effects are not found in patients with higher collagen cross-linking (low CITP:MMP-1).

Published
2022

11. Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial

Author

Verdonschot, Job A. J., Ferreira, João Pedro, Pellicori, Pierpaolo, Brunner-La Rocca, Hans-Peter, Clark, Andrew L., Cosmi, Franco, Cuthbert, Joe, Girerd, Nicolas, Mariottoni, Beatrice, Petutschnigg, Johannes, Rossignol, Patrick, Cleland, John G. F., Zannad, Faiez, Heymans, Stephane R. B., HOMAGE \\'Heart Omics in AGEing\\' consortium, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Glasgow, Institute of Health and Wellbeing, University of Glasgow-Gartnavel General Hospital, Glasgow, Robertson Centre for Biostatistics & Clinical Trials Unit, University of Hull [United Kingdom], Castle Hill Hospital, Cortona Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), The research leading to these results has received funding from the EuropeanUnion Commission’s Seventh Framework programme under Grant AgreementNo. 305507 (HOMAGE). S.H: This manuscript has been possible thanks to thesupport of the Netherlands Cardiovascular Research Initiative, an initiativewith support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10,CVON She-PREDICTS, Grant 2017-21., European Project: 305507, Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, RS: Carim - H02 Cardiomyopathy, Cardiologie, and MUMC+: MA Med Staf Spec Cardiologie (9)

Subjects
Male, Proteomics, Cardiac & Cardiovascular Systems, Time Factors, Proteome, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, 030204 cardiovascular system & hematology, Spironolactone, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Natriuretic peptide, Prospective Studies, Original Investigation, Mineralocorticoid Receptor Antagonists, 0303 health sciences, Diabetes, Blood Proteins, GROWTH-DIFFERENTIATION FACTOR-15, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Biomarker (medicine), Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, medicine.drug_class, Heart failure, Risk Assessment, 03 medical and health sciences, Endocrinology & Metabolism, INFLAMMATION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Predictive Value of Tests, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Diseases of the circulatory (Cardiovascular) system, Humans, 030304 developmental biology, Aged, Proteomic Profile, Science & Technology, business.industry, Biomarker, medicine.disease, Omics, Fibrosis, Blood pressure, chemistry, RC666-701, Cardiovascular System & Cardiology, business, Biomarkers
Abstract

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®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.

Published
2021

12. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology

Author

Ida G. Lunde, Carsten Tschöpe, Johann Bauersachs, Faiez Zannad, Sanjay K Prasad, Gerasimos Filippatos, Xiao-Jun Du, Carlo G. Tocchetti, Piero Pollesello, Natalia López-Andrés, Wolfram-Hubertus Zimmermann, Theresa McDonagh, Manuel Mayr, Christoph Maack, Paul Ford, Stephane Heymans, Thomas Thum, Rudolf A. de Boer, Dirk L. Brutsaert, Alexander R. Lyon, John G.F. Cleland, Joost P.G. Sluijter, Frank R. Heinzel, Kenneth E. Lipson, Frank Ruschitzka, Gilles W. De Keulenaer, Merry L. Lindsey, Javier Díez, BOZEC, Erwan, HOMAGE (Heart Omics in Ageing consortium) - 305507 - INCOMING, Targeting cardiac fibrosis for heart failure treatment - FIBRO-TARGETS - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 602904 - VALID, Hepatic and Cardiac Toxicity Systems modelling - HECATOS - - EC:FP7:HEALTH2013-10-01 - 2018-09-30 - 602156 - VALID, University Medical Center Groningen [Groningen] (UMCG), University of Antwerp (UA), Hannover Medical School [Hannover] (MHH), University of Glasgow, Center for Applied Medical Research [Plamplona] (CIMA), Universidad de Navarra [Pamplona] (UNAV), Clínica Universidad de Navarra [Pamplona], Baker Heart and Diabetes Institute (AUSTRALIA), Galecto Biotech, Charité Campus Virchow-Klinikum (CVK), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], FibroGen Inc., King's College Hospital (KCH), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA)-Universidad de Navarra [Pamplona] (UNAV)-Clínica Universidad de Navarra [Pamplona], University of Oslo (UiO), Oslo University Hospital [Oslo], Royal Brompton Hospital, Orion Pharma, University of Naples Federico II = Università degli studi di Napoli Federico II, King‘s College London, University Medical Center [Utrecht], Institute of Molecular and Translational Therapeutic Strategies (IMTTS), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University Medical Center Göttingen (UMG), University hospital of Zurich [Zurich], University General Hospital ' Attikon ' [Athens, Greece], University of Mississippi Medical Center (UMMC), University of Würzburg = Universität Würzburg, University Hospital Wuerzburg / Universitäts­klinikum Würzburg, Maastricht University [Maastricht], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The Netherlands Heart Institute, R.A.d.B. is supported by the Netherlands Heart Foundation (CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21, and CVON RED-CVD, grant 2017-11), and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). J.B. is supported is supported by the Deutsche Forschungsgemeinschaft (DFG), Clinical Research Group 311 (KFO 311) ‘(Pre)terminal heart and lung failure: unloading and repair’ (DFG, TP1, BA 1742/9-1) and ‘MR-Focus’‘ (DFG BA 1742/8-1). J.S. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (consolidator grant Evicare #725229) and by the Netherlands Heart Foundation (CVON-HUSTCARE). M.M. is a BHF Chair Holder (CH/16/3/32406), with BHF program grant support (RG/16/14/32397), and was awarded a BHF Special Project grant to participate in the ERA-CVD Translational Grant MacroERA. M.M. and T.T. are members of a network funded by the Foundation Leducq. C.G.T. is supported by a Federico II University/Ricerca di Ateneo grant. S.H. has received funding from the European Union Commission's Seventh Framework programme under grant agreement n. 305507 (HOMAGE), n. 602904 (FIBROTARGETS) and FP7-Health-2013-Innovations-1 n. 602156 (HECATOS), CVON2016-Early HFPEF, 2015-10, and CVON SHE-PREDICTS-HF, grant 2017-21. C.M. is supported by the DFG (Ma 2528/7-1, SFB 894, TRR-219) and the Federal Ministry of Education and Science (BMBF, 01EO150, CF.3, RC2)., European Project: 305507, European Project: 602904,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,FIBRO-TARGETS(2013), European Project: 602156,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,HECATOS(2013), de Boer, Rudolf A, De Keulenaer, Gille, Bauersachs, Johann, Brutsaert, Dirk, Cleland, John G, Diez, Javier, Du, Xiao-Jun, Ford, Paul, Heinzel, Frank R, Lipson, Kenneth E, Mcdonagh, Theresa, Lopez-Andres, Natalia, Lunde, Ida G, Lyon, Alexander R, Pollesello, Piero, Prasad, Sanjay K, Tocchetti, Carlo G, Mayr, Manuel, Sluijter, Joost P G, Thum, Thoma, Tschöpe, Carsten, Zannad, Faiez, Zimmermann, Wolfram-Hubertu, Ruschitzka, Frank, Filippatos, Gerasimo, Lindsey, Merry L, Maack, Christoph, Heymans, Stephane, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: CARIM - R2.02 - Cardiomyopathy, RS: Carim - H02 Cardiomyopathy, University of Zurich, and Cardiovascular Centre (CVC)

Subjects
Cardiac & Cardiovascular Systems, Fibrosi, Myocardium/metabolism, Infarction, 030204 cardiovascular system & hematology, Heart Failure/diagnosis, Imaging, Translational Research, Biomedical, 0302 clinical medicine, Fibrosis, Fibrosis/classification, Myocardial infarction, Disease management (health), Non-U.S. Gov't, 1102 Cardiorespiratory Medicine and Haematology, Translational Medical Research, Societies, Medical, Extracellular Matrix Proteins, MOLECULAR-MECHANISMS, Research Support, Non-U.S. Gov't, Cardiac Imaging Techniques/methods, Disease Management, CARDIAC FIBROBLASTS, Prognosis, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Europe, HFA Position Statement, PRESERVED EJECTION FRACTION, Galectin-3, 10209 Clinic for Cardiology, Cardiology, Fibroblast, DIFFUSE MYOCARDIAL FIBROSIS, INFARCTION, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, INTERSTITIAL FIBROSIS, Extracellular Matrix Proteins/blood, medicine.medical_specialty, Myocarditis, INHIBITION, 610 Medicine & health, Translational research, Heart failure, Research Support, 2705 Cardiology and Cardiovascular Medicine, 03 medical and health sciences, LEFT-VENTRICULAR DYSFUNCTION, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Medical, medicine, EXTRACELLULAR-MATRIX, Journal Article, Humans, GALECTIN-3, Science & Technology, Matrix, business.industry, Myocardium, Research, Biomarker, medicine.disease, Cardiac Imaging Techniques, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Biomarkers, Human medicine, business, Societies, Biomarkers/blood
Abstract

Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins - resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:21 issue:3 pages:272-285 ispartof: location:England status: published

Published
2019

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