Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry

Elshorbagy A. Vallejo-Vaz A.J. Barkas F. Lyons A.R.M. Stevens C.A.T. Dharmayat K.I. Catapano A.L. Freiberger T. Hovingh G.K. Mata P. Raal F.J. Santos R.D. Soran H. Watts G.F. Abifadel M. Aguilar-Salinas C.A. Alhabib K.F. Alkhnifsawi M. Almahmeed W. Alnouri F. Alonso R. Al-Rasadi K. Al-Sarraf A. Arca M. Ashavaid T.F. Averna M. Banach M. Becker M. Binder C.J. Bourbon M. Brunham L.R. Chlebus K. Corral P. Cruz D. Davletov K. Descamps O.S. Dwiputra B. Ezhov M. Groselj U. Harada-Shiba M. Holven K.B. Humphries S.E. Kayikcioglu M. Khovidhunkit W. Lalic K. Latkovskis G. Laufs U. Liberopoulos E. Lima-Martinez M.M. Maher V. Marais A.D. März W. Mirrakhimov E. Miserez A.R. Mitchenko O. Nawawi H. Nordestgaard B.G. Panayiotou A.G. Paragh G. Petrulioniene Z. Pojskic B. Postadzhiyan A. Reda A. Reiner Ž. Reyes X. Sadiq F. Sadoh W.E. Schunkert H. Shek A.B. Stroes E. Su T.-C. Subramaniam T. Susekov A.V. Tilney M. Tomlinson B. Truong T.H. Tselepis A.D. Tybjærg-Hansen A. Vázquez-Cárdenas A. Viigimaa M. Vohnout B. Yamashita S. Ray K.K.
21 March 2025 Oxford University Press

European Heart Journal
2025 #46 Issue 12 1127 - 1140 pp.

Background and Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general popuAims lation, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. Methods Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization–defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD. Results Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77–48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10–2.63 and odds ratio 1.65, 95% confidence interval 1.27–2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations. Conclusions Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.

Adiposity , Atherosclerosis , Dyslipidaemia , Insulin resistance

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Department of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London, W12 0BZ, United Kingdom
Department of Physiology, Faculty of Medicine, University of Alexandria, Mowassat Campus, Alexandria, Egypt
Clinical Epidemiology and Vascular Risk, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío, Universidad de Sevilla/CSIC, Seville, Spain
Faculty of Medicine, Department of Medicine, University of Seville, Seville, Spain
Centro de Investigación Biomédica en Red (CIBER) de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain
Faculty of Medicine, Department of Internal Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, Milan, Italy
Centre for Cardiovascular Surgery and Transplantation, Medical Faculty, Masaryk University, Brno, Czech Republic
CarDia, National Institute for Metabolic and Cardiovascular Disease Research, Czech Republic
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
Novo Nordisk, Soborg, Denmark
Fundación Hipercolesterolemia Familiar, Madrid, Spain
Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Heart Institute (InCor), University of São Paulo, Hospital Israelita Albert Einstein, São Paulo, Brazil
Manchester University NHS Foundation Trust, Manchester, United Kingdom
Faculty of Health and Medical Sciences, School of Medicine, University of Western Australia, Perth, WA, Australia
Department of Cardiology, Lipid Disorders Clinic, Cardiometabolic Services, Royal Perth Hospital, Perth, WA, Australia
Faculty of Pharmacy, Laboratory of Biochemistry and Molecular Therapeutics, Saint Joseph University, Beirut, Lebanon
Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
Department of Cardiac Sciences, King Fahad Cardiac Centre, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
College of Pharmacy, University of Al Qadisiyah, Al Diwaniyah, Iraq
College of Medicine, University of Warith Al-Anbiyaa, Karbala, Iraq
Cleveland Clinic Abu Dhabi, Heart and Vascular Institute, Abu Dhabi, United Arab Emirates
Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh, Saudi Arabia
Centre for Advanced Metabolic Medicine and Nutrition, Santiago, Chile
Department of Biochemistry, College of Medicine and Health Science, Medical Research Centre, Sultan Qaboos University, Muscat, Oman
Sabah Al Ahmad Cardiac Centre, Kuwait City, Kuwait
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
Department of Laboratory Medicine, PD Hinduja Hospital, Medical Research Centre Mahim, Mumbai, India
Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Palermo, Italy
Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland
Department of Cardiology and Congenital Diseases of Adults, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland
Department of Pediatric Endocrinology and Diabetology, Centre hospitalier de Luxembourg, Luxembourg City, Luxembourg
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Unidade de Investigação e Desenvolvimento, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal
Faculty of Sciences, Biosystems and Integrative Sciences Institute (BioISI), University of Lisbon, Lisbon, Portugal
Departments of Medicine and Medical Genetics, Centre for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada
1st Department of Cardiology, Medical University of Gdańsk, National Centre of Familial Hypercholesterolaemia in Gdańsk, Gdańsk, Poland
Pharmacology Department, FASTA University, School of Medicine, Mar del Plata, Argentina
Portuguese Atherosclerosis Society, Lisbon, Portugal
Research Health Institute, Al Farabi Kazakh National University, Almaty, Kazakhstan
Centres Hospitaliers Universitaires HELORA at La Louvière, University of Mons, Mons, Belgium
Faculty of Medicine, Department of Cardiology and Vascular Medicine, Universitas Indonesia—Harapan Kita National Cardiovascular Center, Jakarta, Indonesia
National Medical Research Centre of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russian Federation
Department of Paediatric Endocrinology, Diabetes and Metabolism, University Medical Centre, University Children’s Hospital Ljubljana, Ljubljana, Slovenia
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Osaka Medical and Pharmaceutical University, Takatsuki, Japan
National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway
Centre for Cardiovascular Genetics, Institute for Cardiovascular Science, University College London, London, United Kingdom
Department of Cardiology, Ege University Medical School, İzmir, Turkey
Faculty of Medicine, Department of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University of Belgrade, Belgrade, Serbia
Faculty of Medicine, Research Institute of Cardiology and Regenerative Medicine, University of Latvia, Pauls Stradins Clinical University Hospital, Riga, Latvia
Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany
First Department of Propaedeutic and Internal Medicine, School of Medicine, National and Kapodistian University of Athens, Athens, Greece
Universidad de Oriente, Núcleo Bolívar, Ciudad Bolívar, Venezuela
Advanced Lipid Management and Research Centre (ALMAR), Tallaght University Hospital, Dublin, Ireland
Chemical Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
DACH Society for the Prevention of Heart and Circulatory Diseases, Hamburg, Germany
Medical Faculty Mannheim, Department of Internal Medicine, Heidelberg University, Mannheim, Germany
Klinisches Institut für Medizinische und Chemische Labordiagnostik, Medizinische Universität Graz, Graz, Austria
Synlab Akademie, Synlab Holding Deutschland, Augsburg, Mannheim, Germany
Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
College of Medicine, Korea University, Seoul, South Korea
Diagene Research Institute, Swiss Society for Familial Forms of Hypercholesterolemia (SSFH), Reinach, Switzerland
Faculty of Medicine, University of Basel, Basel, Switzerland
Department of Dyslipidaemia, Institute of Cardiology, National Academy of Medical Sciences, Kiev, Ukraine
Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM), Faculty of Medicine, Universiti Teknologi MARA (UiTM), Selangor, Sungai Buloh, Malaysia
Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
Department of Rehabilitation Sciences, School of Health Sciences, Cyprus University of Technology, Limassol, Cyprus
Faculty of Medicine, Division of Metabolic Diseases, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
Vilnius University Faculty of Medicine, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
Faculty of Medicine, Cantonal Hospital Zenica, University of Zenica, Zenica, Bosnia and Herzegovina
Medical University of Sofia, Sofia, Bulgaria
Faculty of Medicine, Department of Cardiology, Menoufia University, Al Minufiyah, Egypt
Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
GENYCO Program, Comisión Honoraria para la Salud Cardiovascular, Montevideo, Uruguay
Directorate of Research, Shifa Tameer-e-Millat University, Islamabad, Pakistan
Department of Child Health, University of Benin Teaching Hospital, Benin City, Nigeria
Clinic for Heart and Circulatory Diseases, German Heart Centre Munich, Technical University Munich, Munich, Germany
German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich, Germany
Department of Coronary Heart Disease and Atherosclerosis, Republican Specialized Centre of Cardiology, Ministry of Health of Republic Uzbekistan, Tashkent, Uzbekistan
Department of Vascular Medicine, AMC, D3.330, Meibergdreef 9, Amsterdam, 1105 AZ, Netherlands
Departments of Environmental and Occupational Medicine, and Internal Medicine (Cardiology Division), National Taiwan University Hospital, Taipei, Taiwan
Admiralty Medical Centre, Khoo Teck Puat Hospital, Yishun Health, Singapore
Federal State Budgetary Educational Institution of Further Professional Education, Russian Medical Academy of Continuous Professional Education”, The Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation
Lipid Clinic, Mater Dei Hospital, Msida, Malta
Faculty of Medicine and Surgery, Department of Medicine, University of Malta, Msida, Malta
Faculty of Medicine, Macau University of Science and Technology, Macao
Faculty of Medicine, Phenikaa University, Vietnam Atherosclerosis Society, Hanoi, Viet Nam
Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece
Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
Departamento Académico Ciclo de Vida, Universidad Autónoma de Guadalajara, Av. Patria 1201, Zapopan, 45129, Mexico
North Estonia Medical Centre, Tallinn University of Technology, Tallinn, Estonia
Department of Diabetology, LF SZU, Institute of Nutrition, FOaZOS, Coordination Centre for Familial Hyperlipidemias, Slovak Medical University in Bratislava, Bratislava, Slovakia
Rinku General Medical Centre, Osaka, Japan

Department of Primary Care and Public Health
Department of Physiology
Clinical Epidemiology and Vascular Risk
Faculty of Medicine
Centro de Investigación Biomédica en Red (CIBER) de Epidemiología y Salud Pública
Faculty of Medicine
Department of Pharmacological and Biomolecular Sciences
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica
Centre for Cardiovascular Surgery and Transplantation
CarDia
Department of Vascular Medicine
Novo Nordisk
Fundación Hipercolesterolemia Familiar
Carbohydrate and Lipid Metabolism Research Unit
Heart Institute (InCor)
Manchester University NHS Foundation Trust
Faculty of Health and Medical Sciences
Department of Cardiology
Faculty of Pharmacy
Unidad de Investigación de Enfermedades Metabólicas
Tecnológico de Monterrey
Department of Cardiac Sciences
College of Pharmacy
College of Medicine
Cleveland Clinic Abu Dhabi
Cardiovascular Prevention Unit
Centre for Advanced Metabolic Medicine and Nutrition
Department of Biochemistry
Sabah Al Ahmad Cardiac Centre
Department of Translational and Precision Medicine
Department of Laboratory Medicine
Department of Health Promotion Sciences
Istituto di Biofisica
Department of Preventive Cardiology and Lipidology
Department of Cardiology and Congenital Diseases of Adults
Cardiovascular Research Centre
Department of Pediatric Endocrinology and Diabetology
Department of Laboratory Medicine
Unidade de Investigação e Desenvolvimento
Faculty of Sciences
Departments of Medicine and Medical Genetics
1st Department of Cardiology
Pharmacology Department
Portuguese Atherosclerosis Society
Research Health Institute
Centres Hospitaliers Universitaires HELORA at La Louvière
Faculty of Medicine
National Medical Research Centre of Cardiology
Department of Paediatric Endocrinology
Faculty of Medicine
Osaka Medical and Pharmaceutical University
National Advisory Unit on Familial Hypercholesterolemia
Centre for Cardiovascular Genetics
Department of Cardiology
Faculty of Medicine
Faculty of Medicine
Faculty of Medicine
Klinik und Poliklinik für Kardiologie
First Department of Propaedeutic and Internal Medicine
Universidad de Oriente
Advanced Lipid Management and Research Centre (ALMAR)
Chemical Pathology
DACH Society for the Prevention of Heart and Circulatory Diseases
Medical Faculty Mannheim
Klinisches Institut für Medizinische und Chemische Labordiagnostik
Synlab Akademie
Kyrgyz State Medical Academy
College of Medicine
Diagene Research Institute
Faculty of Medicine
Department of Dyslipidaemia
Institute of Pathology
Herlev and Gentofte Hospital
Department of Rehabilitation Sciences
Faculty of Medicine
Vilnius University Faculty of Medicine
Faculty of Medicine
Medical University of Sofia
Faculty of Medicine
Department of Internal Medicine
GENYCO Program
Directorate of Research
Department of Child Health
Clinic for Heart and Circulatory Diseases
German Centre for Cardiovascular Research
Department of Coronary Heart Disease and Atherosclerosis
Department of Vascular Medicine
Departments of Environmental and Occupational Medicine
Admiralty Medical Centre
Federal State Budgetary Educational Institution of Further Professional Education
Lipid Clinic
Faculty of Medicine and Surgery
Faculty of Medicine
Faculty of Medicine
Atherothrombosis Research Centre
Rigshospitalet
Departamento Académico Ciclo de Vida
North Estonia Medical Centre
Department of Diabetology
Rinku General Medical Centre

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