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.

1st Department of Cardiology Medical University of Gdańsk National Centre of Familial Hypercholesterolaemia in Gdańsk Gdańsk Poland

1st Department of Propaedeutic and Internal Medicine School of Medicine National and Kapodistian University of Athens Athens Greece

Admiralty Medical Centre and Khoo Teck Puat Hospital Yishun Health Singapore

Advanced Lipid Management and Research Centre Tallaght University Hospital Dublin Ireland

Atherothrombosis Research Centre University of Ioannina Ioannina Greece

Carbohydrate and Lipid Metabolism Research Unit Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

CarDia National Institute for Metabolic and Cardiovascular Disease Research Czech Republic

Cardiovascular Prevention Unit Adult Cardiology Department Prince Sultan Cardiac Centre Riyadh Saudi Arabia

Cardiovascular Research Centre University of Zielona Gora Zielona Gora Poland

Centre for Advanced Metabolic Medicine and Nutrition Santiago Chile

Centre for Cardiovascular Genetics Institute for Cardiovascular Science University College London London UK

Centre for Cardiovascular Surgery and Transplantation and Medical Faculty Masaryk University Brno Czech Republic

Centres Hospitaliers Universitaires HELORA at La Louvière and University of Mons Mons Belgium

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública Instituto de Salud Carlos 3 Madrid Spain

Chemical Pathology University of Cape Town Health Science Faculty Cape Town South Africa

Cleveland Clinic Abu Dhabi Heart and Vascular Institute Abu Dhabi United Arab Emirates

Clinic for Heart and Circulatory Diseases German Heart Centre Munich Technical University Munich Munich Germany

Clinical Epidemiology and Vascular Risk Instituto de Biomedicina de Sevilla IBiS Hospital Universitario Virgen del Rocío Universidad de Sevilla CSIC Seville Spain

College of Medicine Korea University Seoul Korea

College of Medicine University of Warith Al Anbiyaa Karbala Iraq

College of Pharmacy University of Al Qadisiyah Al Diwaniyah Iraq

DACH Society for the Prevention of Heart and Circulatory Diseases Hamburg Germany

Departamento Académico Ciclo de Vida Universidad Autónoma de Guadalajara Av Patria 1201 Zapopan 45129 México

Department of Biochemistry College of Medicine and Health Science and Medical Research Centre Sultan Qaboos University Muscat Oman

Department of Cardiac Sciences King Fahad Cardiac Centre College of Medicine King Saud University Medical City King Saud University Riyadh Saudi Arabia

Department of Cardiology and Congenital Diseases of Adults Polish Mother's Memorial Hospital Research Institute Lodz Poland

Department of Cardiology Ege University Medical School İzmir Turkey

Department of Cardiology Lipid Disorders Clinic Cardiometabolic Services Royal Perth Hospital Perth WA Australia

Department of Child Health University of Benin Teaching Hospital Benin City Nigeria

Department of Coronary Heart Disease and Atherosclerosis Republican Specialized Centre of Cardiology Ministry of Health of Republic Uzbekistan Tashkent Uzbekistan

Department of Diabetology LF SZU Institute of Nutrition FOaZOS Coordination Centre for Familial Hyperlipidemias Slovak Medical University in Bratislava Bratislava Slovakia

Department of Dyslipidaemia Institute of Cardiology National Academy of Medical Sciences Kiev Ukraine

Department of Health Promotion Sciences Maternal and Infantile Care Internal Medicine and Medical Specialties University of Palermo Palermo Italy

Department of Internal Medicine University Hospital Centre Zagreb and School of Medicine University of Zagreb Zagreb Croatia

Department of Laboratory Medicine Medical University of Vienna Vienna Austria

Department of Laboratory Medicine PD Hinduja Hospital and Medical Research Centre Mahim Mumbai India

Department of Paediatric Endocrinology Diabetes and Metabolism University Medical Centre University Children's Hospital Ljubljana Ljubljana Slovenia

Department of Pediatric Endocrinology and Diabetology Centre hospitalier de Luxembourg Luxembourg City Luxembourg

Department of Pharmacological and Biomolecular Sciences University of Milan Milan Italy

Department of Physiology Faculty of Medicine University of Alexandria Mowassat Campus Alexandria Egypt

Department of Preventive Cardiology and Lipidology Medical University of Lodz Lodz Poland

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

Department of Rehabilitation Sciences School of Health Sciences Cyprus University of Technology Limassol Cyprus

Department of Translational and Precision Medicine Sapienza University of Rome Rome Italy

Department of Vascular Medicine Amsterdam UMC University of Amsterdam Amsterdam The Netherlands

Department of Vascular Medicine D3 330 AMC Meibergdreef 9 Amsterdam 1105 AZ The Netherlands

Departments of Environmental and Occupational Medicine and Internal Medicine National Taiwan University Hospital Taipei Taiwan

Departments of Medicine and Medical Genetics Centre for Heart Lung Innovation The University of British Columbia Vancouver Canada

Diagene Research Institute and Swiss Society for Familial Forms of Hypercholesterolemia Reinach Switzerland

Directorate of Research Shifa Tameer e Millat University Islamabad Pakistan

Faculty of Health and Medical Sciences School of Medicine University of Western Australia Perth WA Australia

Faculty of Medicine and Surgery Department of Medicine University of Malta Msida Malta

Faculty of Medicine Cantonal Hospital Zenica University of Zenica Zenica Bosnia and Herzegovina

Faculty of Medicine Clinic for Endocrinology Diabetes and Metabolic Diseases University of Belgrade Belgrade Serbia

Faculty of Medicine Department of Cardiology and Vascular Medicine Universitas Indonesia Harapan Kita National Cardiovascular Center Jakarta Indonesia

Faculty of Medicine Department of Cardiology Menoufia University Al Minufiyah Egypt

Faculty of Medicine Department of Internal Medicine School of Health Sciences University of Ioannina Ioannina Greece

Faculty of Medicine Department of Medicine Chulalongkorn University and King Chulalongkorn Memorial Hospital Bangkok Thailand

Faculty of Medicine Department of Medicine University of Seville Seville Spain

Faculty of Medicine Division of Metabolic Diseases Department of Internal Medicine University of Debrecen Debrecen Hungary

Faculty of Medicine Macau University of Science and Technology Macau China

Faculty of Medicine Phenikaa University Vietnam Atherosclerosis Society Hanoi Vietnam

Faculty of Medicine Research Institute of Cardiology and Regenerative Medicine University of Latvia Pauls Stradins Clinical University Hospital Riga Latvia

Faculty of Medicine University of Basel Basel Switzerland

Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Faculty of Pharmacy Laboratory of Biochemistry and Molecular Therapeutics Saint Joseph University Beirut Lebanon

Faculty of Sciences Biosystems and Integrative Sciences Institute University of Lisbon Lisbon Portugal

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

Fundación Hipercolesterolemia Familiar Madrid Spain

GENYCO Program Comisión Honoraria para la Salud Cardiovascular Montevideo Uruguay

German Centre for Cardiovascular Research Partner Site Munich Heart Alliance Munich Germany

Heart Institute University of São Paulo and Hospital Israelita Albert Einstein São Paulo Brazil

Herlev and Gentofte Hospital Copenhagen University Hospital University of Copenhagen Copenhagen Denmark

Institute of Pathology Laboratory and Forensic Medicine Sungai Buloh Selangor Malaysia

Istituto di Biofisica Consiglio Nazionale delle Ricerche Palermo Italy

Istituto di Ricovero e Cura a Carattere Scientifico MultiMedica Milan Italy

Klinik und Poliklinik für Kardiologie Universitätsklinikum Leipzig Leipzig Germany

Klinisches Institut für Medizinische und Chemische Labordiagnostik Medizinische Universität Graz Graz Austria

Kyrgyz State Medical Academy Bishkek Kyrgyzstan

Lipid Clinic Mater Dei Hospital Msida Malta

Manchester University NHS Foundation Trust Manchester UK

Medical Faculty Mannheim Department of Internal Medicine Heidelberg University Mannheim Germany

Medical University of Sofia Sofia Bulgaria

National Advisory Unit on Familial Hypercholesterolemia Oslo University Hospital Oslo Norway

National Medical Research Centre of Cardiology of Ministry of Health of the Russian Federation Moscow Russia

North Estonia Medical Centre Tallinn University of Technology Tallinn Estonia

Novo Nordisk Soborg Denmark

Osaka Medical and Pharmaceutical University Takatsuki Japan

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

Rigshospitalet Copenhagen University Hospital University of Copenhagen Copenhagen Denmark

Rinku General Medical Centre Osaka Japan

Sabah Al Ahmad Cardiac Centre Kuwait City Kuwait

Synlab Akademie Synlab Holding Deutschland Mannheim and Augsburg Germany

Tecnológico de Monterrey Escuela de Medicina y Ciencias de la Salud Monterrey Mexico

Unidad de Investigación de Enfermedades Metabólicas Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City México

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

Universidad de Oriente Núcleo Bolívar Ciudad Bolívar Venezuela

Vilnius University Faculty of Medicine and Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

Komentář v

doi: 10.1093/eurheartj/ehae810 PubMed

Zobrazit více v PubMed

Mensah  GA, Fuster  V, Murray  CJL, Roth  GA. Global burden of cardiovascular diseases and risks, 1990–2022. J Am Coll Cardiol  2023;82:2350–473. 10.1016/j.jacc.2023.11.007 PubMed DOI PMC

Malik  VS, Willet  WC, Hu  FB. Nearly a decade on - trends, risk factors and policy implications in global obesity. Nat Rev Endocrinol  2020;16:615–6. 10.1038/s41574-020-00411-y PubMed DOI PMC

NCD Risk Factor Collaboration (NCD-RisC) . Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants. Lancet  2020;396:1511–24. 10.1016/S0140-6736(20)31859-6 PubMed DOI PMC

Mongraw-Chaffin  ML, Peters  SAE, Huxley  RR, Woodward  M. The sex-specific association between BMI and coronary heart disease: a systematic review and meta-analysis of 95 cohorts with 1.2 million participants. Lancet Diabetes Endocrinol  2015;3:437–49. 10.1016/S2213-8587(15)00086-8 PubMed DOI PMC

Virani  SS, Alonso  A, Aparicio  HJ, Benjamin  EJ, Bittencourt  MS, Callaway  CW, et al.  Heart Disease and Stroke Statistics-2021 update: a report from the American Heart Association. Circulation  2021;143:e254–743. 10.1161/CIR.0000000000000950 PubMed DOI

Timmis  A, Vardas  P, Townsend  N, Torbica  A, Katus  H, De Smedt  D, et al.  European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J  2022;43:716–99. 10.1093/eurheartj/ehab892 PubMed DOI

Quispe  R, Martin  SS, Michos  ED, Lamba  I, Blumenthal  RS, Saeed  A, et al.  Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. Eur Heart J  2021;42:4324–32. 10.1093/eurheartj/ehab432 PubMed DOI PMC

Schipper  HS, de Ferranti  S. Atherosclerotic cardiovascular risk as an emerging priority in pediatrics. Pediatrics  2022;150:e2022057956. 10.1542/peds.2022-057956 PubMed DOI

Kivimaki  M, Smith  GD, Timpson  NJ, Lawlor  DA, Batty  GD, Kahonen  M, et al.  Lifetime body mass index and later atherosclerosis risk in young adults: examining causal links using Mendelian randomization in the cardiovascular risk in young Finns study. Eur Heart J  2008;29:2552–60. 10.1093/eurheartj/ehn252 PubMed DOI PMC

EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC) . Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet  2021;398:1713–25. 10.1016/S0140-6736(21)01122-3 PubMed DOI

EAS Familial Hypercholesterolaemia Studies Collaboration; Vallejo-Vaz  AJ, De Marco  M, Stevens  CAT, Akram  A, Freiberger  T, et al.  Overview of the current status of familial hypercholesterolaemia care in over 60 countries - the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Atherosclerosis  2018;277:234–55. 10.1016/j.atherosclerosis.2018.08.051 PubMed DOI

Representatives of the Global Familial Hypercholesterolemia Community; Wilemon  KA, Patel  J, Aguilar-Salinas  C, Ahmed  CD, Alkhnifsawi  M, et al.  Reducing the clinical and public health burden of familial hypercholesterolemia: a global call to action. JAMA Cardiol  2020;5:217–29. 10.1001/jamacardio.2019.5173 PubMed DOI

Beheshti  SO, Madsen  CM, Varbo  A, Nordestgaard  BG. Worldwide prevalence of familial hypercholesterolemia: meta-analyses of 11 million subjects. J Am Coll Cardiol  2020;75:2553–66. 10.1016/j.jacc.2020.03.057 PubMed DOI

Hu  P, Dharmayat  KI, Stevens  CAT, Sharabiani  MTA, Jones  RS, Watts  GF, et al.  Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis. Circulation  2020;141:1742–59. 10.1161/CIRCULATIONAHA.119.044795 PubMed DOI

Dai  H, Much  AA, Maor  E, Asher  E, Younis  A, Xu  Y, et al.  Global, regional, and national burden of ischaemic heart disease and its attributable risk factors, 1990–2017: results from the global burden of disease study 2017. Eur Heart J Qual Care Clin Outcomes  2022;8:50–60. 10.1093/ehjqcco/qcaa076 PubMed DOI PMC

Roth  GA, Mensah  GA, Johnson  CO, Addolorato  G, Ammirati  E, Baddour  LM, et al.  Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol  2020;76:2982–3021. 10.1016/j.jacc.2020.11.010 PubMed DOI PMC

Akioyamen  LE, Genest  J, Chu  A, Inibhunu  H, Ko  DT, Tu  JV. Risk factors for cardiovascular disease in heterozygous familial hypercholesterolemia: a systematic review and meta-analysis. J Clin Lipidol  2019;13:15–30. 10.1016/j.jacl.2018.10.012 PubMed DOI

Perez de Isla  L, Alonso  R, Mata  N, Fernandez-Perez  C, Muniz  O, Diaz-Diaz  JL, et al.  Predicting cardiovascular events in familial hypercholesterolemia: the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study). Circulation  2017;135:2133–44. 10.1161/CIRCULATIONAHA.116.024541 PubMed DOI

EAS Familial Hypercholesterolaemia Studies Collaboration; Vallejo-Vaz  AJ, Akram  A, Kondapally Seshasai  SR, Cole  D, Watts  GF, et al.  Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atheroscler Suppl  2016;22:1–32. 10.1016/j.atherosclerosissup.2016.10.001 PubMed DOI

World Health Organization . WHO Factsheets: Obesity and Overweight 2021. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (May 2024, date last accessed).

World Health Organization . BMI-for-age (5–19 years). https://www.who.int/toolkits/growth-reference-data-for-5to19-years/indicators/bmi-for-age (January 2024, date last accessed).

World Health Organization 2000 . The Asia-Pacific Perspective: Redefining Obesity and Its Treatment. https://iris.who.int/handle/10665/206936 (November 2024, date last accessed).

Schumacher  D. Anthroplus: Computation of the WHO 2007 References for School-Age Children and Adolescents (5 to 19 Years). R package version 0.9.0. https://CRAN.R-project.org/package=anthroplus (November 2024, date last accessed).

World Health Organization . BMI-for-age z-score Tables (girls 5–19 years). https://cdn.who.int/media/docs/default-source/child-growth/growth-reference-5-19-years/bmi-for-age-(5-19-years)/bmifa-girls-5-19years-z.pdf?sfvrsn=8f7e5b11_4 (January 2024, date last accessed).

World Health Organization . BMI-for-age z-score Tables (boys 5–19 years).  https://cdn.who.int/media/docs/default-source/child-growth/growth-reference-5-19-years/bmi-for-age-(5-19-years)/bmifa-boys-5-19years-z.pdf?sfvrsn=b74e5f9a_4 (January 2024, date last accessed).

Won  K-B, Heo  R, Park  H-B, Lee  BK, Lin  FY, Hadamitzky  M, et al.  Atherogenic index of plasma and the risk of rapid progression of coronary atherosclerosis beyond traditional risk factors. Atherosclerosis  2021;324:46–51. 10.1016/j.atherosclerosis.2021.03.009 PubMed DOI

Dobiasova  M, Frohlich  J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)). Clin Biochem  2001;34:583–8. 10.1016/S0009-9120(01)00263-6 PubMed DOI

Vallejo-Vaz  AJ, Fayyad  R, Boekholdt  SM, Hovingh  GK, Kastelein  JJ, Melamed  S, et al.  Triglyceride-Rich lipoprotein cholesterol and risk of cardiovascular events among patients receiving statin therapy in the TNT trial. Circulation  2018;138:770–81. 10.1161/CIRCULATIONAHA.117.032318 PubMed DOI

Varbo  A, Benn  M, Tybjaerg-Hansen  A, Jorgensen  AB, Frikke-Schmidt  R, Nordestgaard  BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol  2013;61:427–36. 10.1016/j.jacc.2012.08.1026 PubMed DOI

United Nations Statistics Division . Standard Country or Area Codes for Statistical Use (M49).  https://unstats.un.org/unsd/methodology/m49 (January 2024, date last accessed).

The World Bank . World Bank Country and Lending Groups 2024. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups (January 2024, date last accessed).

Wood  SN. Stable and efficient multiple smoothing parameter estimation for generalized additive models. J Am Stat Assoc  2004;99:673–86. 10.1198/016214504000000980 DOI

Watts  GF, Gidding  SS, Hegele  RA, Raal  FJ, Sturm  AC, Jones  LK, et al.  International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat Rev Cardiol  2023;20:845–69. 10.1038/s41569-023-00892-0 PubMed DOI

NCD Risk Factor Collaboration (NCD-RisC) . Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet  2017;390:2627–42. 10.1016/S0140-6736(17)32129-3 PubMed DOI PMC

Nussbaumerova  B, Rosolova  H. Obesity and dyslipidemia. Curr Atheroscler Rep  2023;25:947–55. 10.1007/s11883-023-01167-2 PubMed DOI

Miettinen  TA, Gylling  H. Cholesterol absorption efficiency and sterol metabolism in obesity. Atherosclerosis  2000;153:241–8. 10.1016/S0021-9150(00)00404-4 PubMed DOI

Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration; Lu  Y, Hajifathalian  K, Ezzati  M, Woodward  M, Rimm  EB, et al.  Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1.8 million participants. Lancet  2014;383:970–83. 10.1016/S0140-6736(13)61836-X PubMed DOI PMC

Kwaifa  IK, Bahari  H, Yong  YK, Noor  SM. Endothelial dysfunction in obesity-induced inflammation: molecular mechanisms and clinical implications. Biomolecules  2020;10:291. 10.3390/biom10020291 PubMed DOI PMC

Jebari-Benslaiman  S, Galicia-Garcia  U, Larrea-Sebal  A, Olaetxea  JR, Alloza  I, Vandenbroeck  K, et al.  Pathophysiology of atherosclerosis. Int J Mol Sci  2022;23:3346. 10.3390/ijms23063346 PubMed DOI PMC

Henning  RJ. Obesity and obesity-induced inflammatory disease contribute to atherosclerosis: a review of the pathophysiology and treatment of obesity. Am J Cardiovasc Dis  2021;11:504–29. https://pubmed.ncbi.nlm.nih.gov/34548951/ PubMed PMC

Lopez-Domenech  S, Martinez-Herrera  M, Abad-Jimenez  Z, Morillas  C, Escribano-Lopez  I, Diaz-Morales  N, et al.  Dietary weight loss intervention improves subclinical atherosclerosis and oxidative stress markers in leukocytes of obese humans. Int J Obes (Lond)  2019;43:2200–9. 10.1038/s41366-018-0309-5 PubMed DOI

Pack  QR, Rodriguez-Escudero  JP, Thomas  RJ, Ades  PA, West  CP, Somers  VK, et al.  The prognostic importance of weight loss in coronary artery disease: a systematic review and meta-analysis. Mayo Clin Proc  2014;89:1368–77. 10.1016/j.mayocp.2014.04.033 PubMed DOI PMC

Sutanto  A, Wungu  CDK, Susilo  H, Sutanto  H. Reduction of Major adverse cardiovascular events (MACE) after bariatric surgery in patients with obesity and cardiovascular diseases: a systematic review and meta-analysis. Nutrients  2021;13:3568. 10.3390/nu13103568 PubMed DOI PMC

Chung  ST, Krenek  A, Magge  SN. Childhood obesity and cardiovascular disease risk. Curr Atheroscler Rep  2023;25:405–15. 10.1007/s11883-023-01111-4 PubMed DOI PMC

Jebeile  H, Kelly  AS, O'Malley  G, Baur  LA. Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol  2022;10:351–65. 10.1016/S2213-8587(22)00047-X PubMed DOI PMC

Mangner  N, Scheuermann  K, Winzer  E, Wagner  I, Hoellriegel  R, Sandri  M, et al.  Childhood obesity: impact on cardiac geometry and function. JACC Cardiovasc Imaging  2014;7:1198–205. 10.1016/j.jcmg.2014.08.006 PubMed DOI

Gjaerde  LK, Gamborg  M, Angquist  L, Truelsen  TC, Sorensen  TIA, Baker  JL. Association of childhood body mass index and change in body mass index with first adult ischemic stroke. JAMA Neurol  2017;74:1312–8. 10.1001/jamaneurol.2017.1627 PubMed DOI PMC

European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration . Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study. Lancet  2024;403:55–66. 10.1016/S0140-6736(23)01842-1 PubMed DOI

McMahan  CA, Gidding  SS, McGill  HC  Jr. Coronary heart disease risk factors and atherosclerosis in young people. J Clin Lipidol  2008;2:118–26. 10.1016/j.jacl.2008.02.006 PubMed DOI

Besseling  J, Kindt  I, Hof  M, Kastelein  JJ, Hutten  BA, Hovingh  GK. Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers. Atherosclerosis  2014;233:219–23. 10.1016/j.atherosclerosis.2013.12.020 PubMed DOI

Jansen  AC, van Aalst-Cohen  ES, Tanck  MW, Trip  MD, Lansberg  PJ, Liem  AH, et al.  The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med  2004;256:482–90. 10.1111/j.1365-2796.2004.01405.x PubMed DOI

Gaudet  D, Vohl  MC, Perron  P, Tremblay  G, Gagne  C, Lesiege  D, et al.  Relationships of abdominal obesity and hyperinsulinemia to angiographically assessed coronary artery disease in men with known mutations in the LDL receptor gene. Circulation  1998;97:871–7. 10.1161/01.CIR.97.9.871 PubMed DOI

Trinder  M, Vikulova  D, Pimstone  S, Mancini  GBJ, Brunham  LR. Polygenic architecture and cardiovascular risk of familial combined hyperlipidemia. Atherosclerosis  2022;340:35–43. 10.1016/j.atherosclerosis.2021.11.032 PubMed DOI