title: Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment.
abstract: Familial hypercholesterolaemia (FH) is a common genetic cause of premature coronary heart disease (CHD). Globally, one baby is born with FH every minute. If diagnosed and treated early in childhood, individuals with FH can have normal life expectancy. This consensus paper aims to improve awareness of the need for early detection and management of FH children. Familial hypercholesterolaemia is diagnosed either on phenotypic criteria, i.e. an elevated low-density lipoprotein cholesterol (LDL-C) level plus a family history of elevated LDL-C, premature coronary artery disease and/or genetic diagnosis, or positive genetic testing. Childhood is the optimal period for discrimination between FH and non-FH using LDL-C screening. An LDL-C ≥5 mmol/L (190 mg/dL), or an LDL-C ≥4 mmol/L (160 mg/dL) with family history of premature CHD and/or high baseline cholesterol in one parent, make the phenotypic diagnosis. If a parent has a genetic defect, the LDL-C cut-off for the child is ≥3.5 mmol/L (130 mg/dL). We recommend cascade screening of families using a combined phenotypic and genotypic strategy. In children, testing is recommended from age 5 years, or earlier if homozygous FH is suspected. A healthy lifestyle and statin treatment (from age 8 to 10 years) are the cornerstones of management of heterozygous FH. Target LDL-C is <3.5 mmol/L (130 mg/dL) if >10 years, or ideally 50% reduction from baseline if 8-10 years, especially with very high LDL-C, elevated lipoprotein(a), a family history of premature CHD or other cardiovascular risk factors, balanced against the long-term risk of treatment side effects. Identifying FH early and optimally lowering LDL-C over the lifespan reduces cumulative LDL-C burden and offers health and socioeconomic benefits. To drive policy change for timely detection and management, we call for further studies in the young. Increased awareness, early identification, and optimal treatment from childhood are critical to adding decades of healthy life for children and adolescents with FH.
authors.affiliation: Department of Paediatrics, Academic Medical Center, University of Amsterdam, The Netherlands a.wiegman@amc.uva.nl.
authors.forename: Albert
authors.initials: A
authors.lastname: Wiegman
authors.affiliation: Nemours Cardiac Center, A. I. DuPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Gidding
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Western Australia, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Pierre and Marie Curie University, Paris, France National Institute for Health and Medical Research (INSERM), Pitié-Salpêtrière University Hospital, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY, USA Irving Institute for Clinical and Translational Research, Columbia University Medical Center, New York, USA.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Cuchel
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors.forename: Leiv
authors.initials: L
authors.lastname: Ose
authors.affiliation: Department of Internal Medicine, University of Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Averna
authors.affiliation: Diderot Medical School, University Paris 7, Paris, France Genetics Department, Bichat University Hospital, Paris, France INSERM U698, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boileau
authors.affiliation: Department of Medicine, Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden Wallenberg Laboratory for Cardiovascular Research, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.affiliation: Department of Endocrinology and Prevention of Cardiovascular Disease, University Hospital Pitié-Salpêtrière, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Milano, Milan, Italy Multimedica IRCSS, Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.affiliation: Centre Hospitalier Jolimont-Lobbes, Nivelles-Tubize, Belgium.
authors.forename: Olivier S
authors.initials: OS
authors.lastname: Descamps
authors.affiliation: Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: Centre for Cardiovascular Genetics, University College London, Institute of Cardiovascular Sciences, London, UK.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.affiliation: Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.affiliation: Vascular Medicine and Metabolic Unit, Department of Medicine and Surgery, University Rovira and Virgili, Reus-Tarragona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Masana
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Department of Human Genetics, Center for Metabolic Disease Prevention, University of California, Los Angeles, USA.
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.affiliation: Department of Endocrinology and Metabolism, University of Munich, Munich, Germany.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Parhofer
authors.affiliation: Carbohydrate & Lipid Metabolism Research Unit; and Division of Endocrinology & Metabolism, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.affiliation: Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: Lipid Clinic of the Heart Institute (InCor), University of São Paulo, São Paulo, Brazil Department of Cardiology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anton F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.affiliation: Evangelisches Geriatriezentrum Berlin gGmbH (EGZB), Berlin, Germany Charité - Universitätsmedizin, Berlin, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Steinhagen-Thiessen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Stroes
authors.affiliation: Research Programs Unit, Diabetes & Obesity, University of Helsinki and Heart & Lung Centre, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.affiliation: Department of Clinical Biochemistry, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: Department of Experimental and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Wiklund
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy; D059168:Carotid Intima-Media Thickness; D002648:Child; D019411:Clinical Laboratory Techniques / Q000379:methods; D017281:Cost of Illness; D003376:Counseling; D004032:Diet; D019587:Dietary Supplements; D042241:Early Diagnosis; D004470:Economics, Medical; D019317:Evidence-Based Medicine; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008017:Life Expectancy; D055118:Medication Adherence; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D012307:Risk Factors; D055815:Young Adult
keywords: Adolescents; Children; Consensus statement; Diagnosis; Ezetimibe; Familial hypercholesterolaemia; LDL cholesterol; PCSK9 inhibitor; Statin; Treatment