Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement

Obesity rates have surged since 1990 worldwide. This rise is paralleled by increases in pathological processes affecting organs such as the heart, liver, and kidneys, here termed systemic metabolic disorders (SMDs). For clinical management of SMD, the European Atherosclerosis Society proposes a pathophysiology-based system comprising three stages: Stage 1, where metabolic abnormalities such as dysfunctional adiposity and dyslipidaemia occur without detectable organ damage; Stage 2, which involves early organ damage manifested as Type 2 diabetes, asymptomatic diastolic dysfunction, metabolic-associated steatohepatitis (MASH), and chronic kidney disease (CKD); and Stage 3, characterized by more advanced organ damage affecting multiple organs. Various forms of high-risk obesity, driven by maintained positive energy balance, are the most common cause of SMD, leading to ectopic lipid accumulation and insulin resistance. This progression affects various organs, promoting comorbidities such as hypertension and atherogenic dyslipidaemia. Genetic factors influence SMD susceptibility, and ethnic disparities in SMD are attributable to genetic and socioeconomic factors. Key SMD features include insulin resistance, inflammation, pre-diabetes, Type 2 diabetes, MASH, hypertension, CKD, atherogenic dyslipidaemia, and heart failure. Management strategies involve lifestyle changes, pharmacotherapy, and metabolic surgery in severe cases, with emerging treatments focusing on genetic approaches. The staging system provides a structured approach to understanding and addressing the multi-faceted nature of SMD, which is crucial for improving health outcomes. Categorization of SMD abnormalities by presence and progression is aimed to improve awareness of a multi-system trait and encourage a tailored and global approach to treatment, ultimately aiming to reduce the burden of obesity-related comorbidities.

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Publication Details

Journal
European Heart Journal
Published
2025-05-07
DOI
https://doi.org/10.1093/eurheartj/ehaf314
Citations
35
Primary Topic
Diet and metabolism studies
Type
article
Field-Weighted Citation Impact
40.75

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article

Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement

Ashraf Reda, Ralph Kwame Akyea, Kausik Kumar Ray, François Pattou et al.
35 citations
European Heart Journal
Diet and metabolism studies
40.75
article

Clinical staging to guide management of metabolic disorders and their sequelae: a European Atherosclerosis Society consensus statement

Ashraf Reda, Ralph Kwame Akyea, Kausik Kumar Ray, François Pattou, Marianne Benn, Oveis Jamialahmadi, Margus Viigimaa, Antonio Vidal‐Puig, Minna Kaikkonen-Määttä, Gema Frühbeck, Daniel Sedding, Stefano Romeo, Carlos Guijarro, Olena Mitchenko, Luigi Fontana, Dan Gaita, Oliver Weingärtner, Roxana Cristina Rimbaş, Susan E. Quaggin, Juan Luis Garcı́a, Jeanine E. Roeters van Lennep, Habib Gamra, Pablo Corral, Belma Pojskić, Julia Kozlitina, Mansoor Husain, Katherine R. Tuttle, М. В. Ежов, Dagmar Kratky, Ulrike Schatz, John Valdes, René Valéro, Erkin М Мirrakhimov, Rosie Perkins, Jogchum Plat, Eva Lonn, Christoph J. Binder, Nicola Segata, Mutaz Al-Khnifsawi, Rexford S. Ahima, Judy de Haan, Subodh Verma, Tea Gamezardashvili, Phivos Symeonides, Roger Foo, Alberico L. Catapano, Paul M. Ridker, Christodoulos Papadopoulos, Tomasz J Guzik, Vincent Maher, Marcello Arca, Märt Elmet, Mikael Rydén, Michal Vrablik, Deepak L Bhatt, György Paragh, Anna Mae Diehl, Lâle Tokgözoğlu, Jaetaek Kim, Haralampos Milionis
article en
35 citations

Abstract

Obesity rates have surged since 1990 worldwide. This rise is paralleled by increases in pathological processes affecting organs such as the heart, liver, and kidneys, here termed systemic metabolic disorders (SMDs). For clinical management of SMD, the European Atherosclerosis Society proposes a pathophysiology-based system comprising three stages: Stage 1, where metabolic abnormalities such as dysfunctional adiposity and dyslipidaemia occur without detectable organ damage; Stage 2, which involves early organ damage manifested as Type 2 diabetes, asymptomatic diastolic dysfunction, metabolic-associated steatohepatitis (MASH), and chronic kidney disease (CKD); and Stage 3, characterized by more advanced organ damage affecting multiple organs. Various forms of high-risk obesity, driven by maintained positive energy balance, are the most common cause of SMD, leading to ectopic lipid accumulation and insulin resistance. This progression affects various organs, promoting comorbidities such as hypertension and atherogenic dyslipidaemia. Genetic factors influence SMD susceptibility, and ethnic disparities in SMD are attributable to genetic and socioeconomic factors. Key SMD features include insulin resistance, inflammation, pre-diabetes, Type 2 diabetes, MASH, hypertension, CKD, atherogenic dyslipidaemia, and heart failure. Management strategies involve lifestyle changes, pharmacotherapy, and metabolic surgery in severe cases, with emerging treatments focusing on genetic approaches. The staging system provides a structured approach to understanding and addressing the multi-faceted nature of SMD, which is crucial for improving health outcomes. Categorization of SMD abnormalities by presence and progression is aimed to improve awareness of a multi-system trait and encourage a tailored and global approach to treatment, ultimately aiming to reduce the burden of obesity-related comorbidities.

European Heart JournalVol. 46(38)
Northwestern University (US), University of Copenhagen (DK), Brigham and Women's Hospital (US), The University of Sydney (AU), St. Michael's Hospital (CA), Karolinska University Hospital (SE), Harvard University (US), Johns Hopkins University (US), National University of Singapore (SG), Duke University (US), University of Toronto (CA), University of Milan (IT), University of Trento (IT), Providence College (US), University of Washington (US), Université de Lille (FR), University of Cambridge (GB), Royal Prince Alfred Hospital (AU), Johns Hopkins Medicine (US), Policlinico Umberto I (IT), Institut Pasteur de Lille (FR), University Health System (US), Sahlgrenska University Hospital (SE), Instituto de Salud Carlos III (ES), Erasmus MC (NL), Inland Northwest Health Services (US), Copenhagen University Hospital (DK), Rigshospitalet (DK), Population Health Research Institute (CA), Karolinska Institutet (SE), Maastricht University (NL), Magna Graecia University (IT), Ted Rogers Centre for Heart Research (CA), MultiMedica (IT), Mount Sinai Hospital (US), Navarre Institute of Health Research (ES), Centro de Investigación Biomédica en Red (ES), Wellcome/MRC Institute of Metabolic Science (GB), Clinica Universidad de Navarra (ES), National University Health System (SG), Addenbrooke's Hospital (GB), MRC Epidemiology Unit (GB), Centro de Investigacion Principe Felipe (ES), Imperial College London (GB), European Institute of Oncology (IT), Hacettepe University (TR), Medical University of Vienna (AT), Hamilton Health Sciences (CA), Sapienza University of Rome (IT), The University of Texas Southwestern Medical Center (US), University of Gothenburg (SE), McMaster University (CA), Icahn School of Medicine at Mount Sinai (US)
American Heart Association, Abbott Laboratories, American Society of Nephrology, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Brigham and Women's Hospital, Alnylam Pharmaceuticals, CSL Behring, Boston Scientific Corporation, Regeneron Pharmaceuticals, Ironwood Pharmaceuticals, Incorporated, Ultragenyx Pharmaceutical, Amarin Corporation, Cytokinetics, Medicines Company, Kowa Company, European Atherosclerosis Society, MyoKardia, Amryt Pharma, Belvoir Media Group, Moderna, Imperial College London, University College London, Fondation Leducq, ZonMw, Universiteit Maastricht, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, University of Toronto, Novo Nordisk, European Association for the Study of Diabetes, Türk Kardiyoloji Derneği, Hellenic Atherosclerosis Society, Tillotts Pharma, Idorsia Pharmaceuticals, HLS Therapeutics, Silence Therapeutics, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Esperion Therapeutics, Canadian Institutes of Health Research, Medical Research Council, National Medical Research Council, Biomedical Research Council, National Heart, Lung, and Blood Institute, Duke Clinical Research Institute, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 0%
Diet and metabolism studies
40.75
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