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

Elshorbagy A 1 , Vallejo-Vaz AJ 1 , Barkas F 1 , Lyons ARM 1 , Stevens CAT 1 , Dharmayat KI 1 Show all authors , Catapano AL 2 , Freiberger T 3 , Hovingh GK 4 , Mata P 5 , Raal FJ 6 , Santos RD 7 , Soran H 8 , Watts GF 9 , Abifadel M 10 , Aguilar-Salinas CA 11 , Alhabib KF 12 , Alkhnifsawi M 13 , Almahmeed W 14 , Alnouri F 15 , Alonso R 16 , Al-Rasadi K 17 , Al-Sarraf A 18 , Arca M 19 , Ashavaid TF 20 , Averna M 21 , Banach M 22 , Becker M 23 , Binder CJ 24 , Bourbon M 25 , Brunham LR 26 , Chlebus K 27 , Corral P 28 , Cruz D 29 , Davletov K 30 , Descamps OS 31 , Dwiputra B 32 , Ezhov M 33 , Groselj U 34 , Harada-Shiba M 35 , Holven KB 36 , Humphries SE 37 , Kayikcioglu M 38 , Khovidhunkit W 39 , Lalic K 40 , Latkovskis G 41 , Laufs U 42 , Liberopoulos E 43 , Lima-Martinez MM 44 , Maher V 45 , Marais AD 46 , März W 47 , Mirrakhimov E 48 , Miserez AR 49 , Mitchenko O 50 , Nawawi H 51 , Nordestgaard BG 52 , Panayiotou AG 53 , Paragh G 54 , Petrulioniene Z 55 , Pojskic B 56 , Postadzhiyan A 57 , Reda A 58 , Reiner Ž 59 , Reyes X 60 , Sadiq F 61 , Sadoh WE 62 , Schunkert H 63 , Shek AB 64 , Stroes E 65 , Su TC 66 , Subramaniam T 67 , Susekov AV 68 , Tilney M 69 , Tomlinson B 70 , Truong TH 71 , Tselepis AD 72 , Tybjærg-Hansen A 73 , Vázquez-Cárdenas A 74 , Viigimaa M 75 , Vohnout B 76 , Yamashita S 77 , Ray KK 1

Affiliations 

  • 1 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, UK
  • 2 Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
  • 3 Centre for Cardiovascular Surgery and Transplantation, and Medical Faculty, Masaryk University, Brno, Czech Republic
  • 4 Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
  • 5 Fundación Hipercolesterolemia Familiar, Madrid, Spain
  • 6 Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  • 7 Heart Institute (InCor), University of São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil
  • 8 Manchester University NHS Foundation Trust, Manchester, UK
  • 9 Faculty of Health and Medical Sciences, School of Medicine, University of Western Australia, Perth, WA, Australia
  • 10 Faculty of Pharmacy, Laboratory of Biochemistry and Molecular Therapeutics, Saint Joseph University, Beirut, Lebanon
  • 11 Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México
  • 12 Department of Cardiac Sciences, King Fahad Cardiac Centre, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
  • 13 College of Pharmacy, University of Al Qadisiyah, Al Diwaniyah, Iraq
  • 14 Cleveland Clinic Abu Dhabi, Heart and Vascular Institute, Abu Dhabi, United Arab Emirates
  • 15 Cardiovascular Prevention Unit, Adult Cardiology Department, Prince Sultan Cardiac Centre, Riyadh, Saudi Arabia
  • 16 Centre for Advanced Metabolic Medicine and Nutrition, Santiago, Chile
  • 17 Department of Biochemistry, College of Medicine and Health Science and Medical Research Centre, Sultan Qaboos University, Muscat, Oman
  • 18 Sabah Al Ahmad Cardiac Centre, Kuwait City, Kuwait
  • 19 Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
  • 20 Department of Laboratory Medicine, PD Hinduja Hospital and Medical Research Centre Mahim, Mumbai, India
  • 21 Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
  • 22 Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland
  • 23 Department of Pediatric Endocrinology and Diabetology, Centre hospitalier de Luxembourg, Luxembourg City, Luxembourg
  • 24 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
  • 25 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
  • 26 Departments of Medicine and Medical Genetics, Centre for Heart Lung Innovation, The University of British Columbia, Vancouver, Canada
  • 27 1st Department of Cardiology Medical University of Gdańsk, National Centre of Familial Hypercholesterolaemia in Gdańsk, Gdańsk, Poland
  • 28 Pharmacology Department, FASTA University, School of Medicine, Mar del Plata, Argentina
  • 29 Portuguese Atherosclerosis Society, Lisbon, Portugal
  • 30 Research Health Institute, Al Farabi Kazakh National University, Almaty, Kazakhstan
  • 31 Centres Hospitaliers Universitaires HELORA at La Louvière and University of Mons, Mons, Belgium
  • 32 Faculty of Medicine, Department of Cardiology and Vascular Medicine, Universitas Indonesia-Harapan Kita National Cardiovascular Center, Jakarta, Indonesia
  • 33 National Medical Research Centre of Cardiology of Ministry of Health of the Russian Federation, Moscow, Russia
  • 34 Department of Paediatric Endocrinology, Diabetes and Metabolism, University Medical Centre, University Children's Hospital Ljubljana, Ljubljana, Slovenia
  • 35 Osaka Medical and Pharmaceutical University, Takatsuki, Japan
  • 36 National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway
  • 37 Centre for Cardiovascular Genetics, Institute for Cardiovascular Science, University College London, London, UK
  • 38 Department of Cardiology, Ege University Medical School, İzmir, Turkey
  • 39 Faculty of Medicine, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  • 40 Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University of Belgrade, Belgrade, Serbia
  • 41 Faculty of Medicine, Research Institute of Cardiology and Regenerative Medicine, University of Latvia, Pauls Stradins Clinical University Hospital, Riga, Latvia
  • 42 Klinik und Poliklinik für Kardiologie, Universitätsklinikum Leipzig, Leipzig, Germany
  • 43 First Department of Propaedeutic and Internal Medicine, School of Medicine, National and Kapodistian University of Athens, Athens, Greece
  • 44 Universidad de Oriente, Núcleo Bolívar, Ciudad Bolívar, Venezuela
  • 45 Advanced Lipid Management and Research Centre (ALMAR), Tallaght University Hospital, Dublin, Ireland
  • 46 Chemical Pathology, University of Cape Town Health Science Faculty, Cape Town, South Africa
  • 47 DACH Society for the Prevention of Heart and Circulatory Diseases, Hamburg, Germany
  • 48 Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
  • 49 Diagene Research Institute and Swiss Society for Familial Forms of Hypercholesterolemia (SSFH), Reinach, Switzerland
  • 50 Department of Dyslipidaemia, Institute of Cardiology, National Academy of Medical Sciences, Kiev, Ukraine
  • 51 Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM) and Faculty of Medicine, Universiti Teknologi MARA (UiTM), Sungai Buloh, Selangor, Malaysia
  • 52 Herlev and Gentofte Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
  • 53 Department of Rehabilitation Sciences, School of Health Sciences, Cyprus University of Technology, Limassol, Cyprus
  • 54 Faculty of Medicine, Division of Metabolic Diseases, Department of Internal Medicine, University of Debrecen, Debrecen, Hungary
  • 55 Vilnius University Faculty of Medicine and Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
  • 56 Faculty of Medicine, Cantonal Hospital Zenica, University of Zenica, Zenica, Bosnia and Herzegovina
  • 57 Medical University of Sofia, Sofia, Bulgaria
  • 58 Faculty of Medicine, Department of Cardiology, Menoufia University, Al Minufiyah, Egypt
  • 59 Department of Internal Medicine, University Hospital Centre Zagreb, and School of Medicine, University of Zagreb, Zagreb, Croatia
  • 60 GENYCO Program, Comisión Honoraria para la Salud Cardiovascular, Montevideo, Uruguay
  • 61 Directorate of Research, Shifa Tameer-e-Millat University, Islamabad, Pakistan
  • 62 Department of Child Health, University of Benin Teaching Hospital, Benin City, Nigeria
  • 63 Clinic for Heart and Circulatory Diseases, German Heart Centre Munich, Technical University Munich, Munich, Germany
  • 64 Department of Coronary Heart Disease and Atherosclerosis, Republican Specialized Centre of Cardiology, Ministry of Health of Republic Uzbekistan, Tashkent, Uzbekistan
  • 65 Department of Vascular Medicine, D3.330, AMC, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands
  • 66 Departments of Environmental and Occupational Medicine, and Internal Medicine (Cardiology Division), National Taiwan University Hospital, Taipei, Taiwan
  • 67 Admiralty Medical Centre and Khoo Teck Puat Hospital, Yishun Health, Singapore
  • 68 Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia
  • 69 Lipid Clinic, Mater Dei Hospital, Msida, Malta
  • 70 Faculty of Medicine, Macau University of Science and Technology, Macau, China
  • 71 Faculty of Medicine, Phenikaa University, Vietnam Atherosclerosis Society, Hanoi, Vietnam
  • 72 Atherothrombosis Research Centre, University of Ioannina, Ioannina, Greece
  • 73 Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
  • 74 Departamento Académico Ciclo de Vida, Universidad Autónoma de Guadalajara, Av. Patria 1201, Zapopan 45129, México
  • 75 North Estonia Medical Centre, Tallinn University of Technology, Tallinn, Estonia
  • 76 Department of Diabetology, LF SZU, Institute of Nutrition, FOaZOS, Coordination Centre for Familial Hyperlipidemias, Slovak Medical University in Bratislava, Bratislava, Slovakia
  • 77 Rinku General Medical Centre, Osaka, Japan
Eur Heart J, 2025 Jan 13.
PMID: 39801189 DOI: 10.1093/eurheartj/ehae791

Abstract

BACKGROUND AND AIMS: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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