Familial Hypercholesterolemia

Amy E. Levenson; Sarah D. de Ferranti

Familial Hypercholesterolemia

Review

In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

2023 Nov 28.

Authors

Amy E. Levenson¹, Sarah D. de Ferranti²

Book Editors

Kenneth R Feingold¹, S. Faisal Ahmed², Bradley Anawalt³, Marc R Blackman⁴, Alison Boyce⁵, George Chrousos⁶, Emiliano Corpas⁷, Wouter W de Herder⁸, Ketan Dhatariya⁹, Kathleen Dungan¹⁰, Johannes Hofland¹¹, Sanjay Kalra¹², Gregory Kaltsas¹³, Nitin Kapoor¹⁴, Christian Koch¹⁵, Peter Kopp¹⁶, Márta Korbonits¹⁷, Christopher S Kovacs¹⁸, Wendy Kuohung¹⁹, Blandine Laferrère²⁰, Miles Levy²¹, Elizabeth A McGee²², Robert McLachlan²³, Radhika Muzumdar²⁴, Jonathan Purnell²⁵, Rodolfo Rey²⁶, Rakesh Sahay²⁷, Amy S Shah²⁸, Frederick Singer²⁹, Mark A Sperling³⁰, Constantine A Stratakis³¹, Dace L Trence³², Don P Wilson³³

Affiliations

¹ Associate Professor of Pediatrics, Division of Pediatric Endocrinology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, United States.
² Associate Professor of Pediatrics, Director of the Preventive Cardiology Clinic and Division Chief, Outpatient Cardiology, Department of Cardiology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.

Book Affiliations

¹ Professor of Medicine Emeritus, University of California, San Francisco, CA
² Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
³ Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
⁴ Sr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
⁵ Pediatric Endocrinologist and Associate Research Physician in the Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health
⁶ Professor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
⁷ M.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
⁸ Professor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
⁹ Consultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
¹⁰ Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
¹¹ Consultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
¹² Consultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
¹³ Professor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
¹⁴ Professor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
¹⁵ Professor, The University of Tennessee Health Science Center, Memphis, Tennessee
¹⁶ Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
¹⁷ Professor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
¹⁸ University Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
¹⁹ Director of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
²⁰ Professor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
²¹ Consultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
²² Professor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
²³ Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
²⁴ Allan L. Drash Endowed Chair, Chief, Division of Endocrinology and Diabetes, UPMC Children’s Hospital of Pittsburgh, Professor of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
²⁵ Professor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
²⁶ Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires; and Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina
²⁷ Professor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
²⁸ Professor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
²⁹ Director of the Endocrine/Bone Disease Program, Saint Johns Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CA
³⁰ Professorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
³¹ CSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
³² Professor of Medicine, Emeritus, University of Washington, Seattle, WA
³³ Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

PMID: 27809433
Bookshelf ID: NBK395572

Excerpt

Familial hypercholesterolemia (FH) is a prevalent, autosomal co-dominant disorder of lipid metabolism that results in elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerosis. Screening for and identifying heterozygous FH in childhood is critical, given its high prevalence and asymptomatic presentation. Furthermore, treatment of FH in childhood is effective at lowering LDL-C levels and has the potential to reduce atherosclerotic cardiovascular disease (ASCVD) events in adulthood. Selective screening based on family history had previously been recommended to identify children and adolescents with FH or other lipid disorders. However, studies indicated that many individuals with heterozygous FH were missed with this approach, and therefore in 2011 the National Heart, Lung, and Blood Institute Expert Panel recommended universal screening of children and adolescents between ages 9 and 11 years and again at ages 17 to 21 years, in addition to selective screening, in order to identify pediatric individuals with heterozygous FH. This approach was affirmed in the 2018 American College of Cardiology and the American Heart Association (ACC/AHA) Cholesterol Guidelines, along with endorsing cascade screening as another reasonable approach to identifying children with FH. Once FH is diagnosed, prompt treatment with lifestyle modification should be initiated. When lifestyle interventions are not sufficient, pharmacotherapy using statins has been shown to be effective at lowering LDL-C, generally safe in short and medium- term studies, and may be beneficial at reducing ASCVD events. Other medications can be useful at lowering LDL-C in conjunction with statin therapy, although generally statins are sufficient in young patients. Homozygous FH is a rare disorder manifesting as extremely high LDL-C and ASCVD in childhood, requiring aggressive multimodal management. Overall, studies are needed to determine the optimal timing and intensity of statin therapy, and to better understand long-term safety and ASCVD outcomes in adulthood for lipid-lowering pharmacotherapy initiated in pediatric patients with heterozygous FH. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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