title: Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel.
abstract: Familial hypercholesterolaemia is common in individuals who had a myocardial infarction at a young age. As many as one in 200 people could have heterozygous familial hypercholesterolaemia, and up to one in 300 000 individuals could be homozygous. The phenotypes of heterozygous and homozygous familial hypercholesterolaemia overlap considerably; the response to treatment is also heterogeneous. In this Review, we aim to define a phenotype for severe familial hypercholesterolaemia and identify people at highest risk for cardiovascular disease, based on the concentration of LDL cholesterol in blood and individuals' responsiveness to conventional lipid-lowering treatment. We assess the importance of molecular characterisation and define the role of other cardiovascular risk factors and advanced subclinical coronary atherosclerosis in risk stratification. Individuals with severe familial hypercholesterolaemia might benefit in particular from early and more aggressive cholesterol-lowering treatment (eg, with PCSK9 inhibitors). In addition to better tailored therapy, more precise characterisation of individuals with severe familial hypercholesterolaemia could improve resource use.
authors.affiliation: Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, and Preventive Medicine Centre and Cardiology Program, Hospital Israelita Albert Einstein, São Paulo, Brazil. Electronic address: rdsf@uol.com.br.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
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: Department of Medicine and Robarts Research Institute, Schulich School of Medicine, Western University, London, ON, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Cuchel
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: Lipid Disorders Clinic, Royal Perth Hospital, The University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Preventive Cardiology, Christine E Lynn Women's Health & Wellness Institute, Boca Raton Regional Hospital, Boca Raton, FL, USA.
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Baum
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; IRCCS Multimedica, Milan, Italy.
authors.forename: Alberico L
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Pitié-Sâlpetrière University Hospital, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: University of Amsterdam, Academic Medical Center (AMC), Amsterdam, Netherlands.
authors.forename: Joep C
authors.initials: JC
authors.lastname: Defesche
authors.affiliation: International Atherosclerosis Society, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Folco
authors.affiliation: Molecular Genetics Lab, Centre for Cardiovascular Surgery and Transplantation, and Ceitec, Masaryk University, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Freiberger
authors.affiliation: McGill University Health Center, Royal Victoria Hospital, Montreal, QC, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
authors.affiliation: University of Amsterdam, Academic Medical Center (AMC), Amsterdam, Netherlands.
authors.forename: G Kees
authors.initials: GK
authors.lastname: Hovingh
authors.affiliation: National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College of London, London, UK.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: International Atherosclerosis Society, Houston, TX, USA.
authors.forename: Ann S
authors.initials: AS
authors.lastname: Jackson
authors.affiliation: Fundación Hipercolesterolemia Familiar, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
authors.affiliation: Atherosclerosis and Lipoprotein-Apheresis Center, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Moriarty
authors.affiliation: Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.affiliation: Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Rasadi
authors.affiliation: School of Public Health, Imperial College London, London, UK.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: European Association for Cardiovascular Prevention and Rehabilitations, Zagreb, Croatia.
authors.forename: Zelijko
authors.initials: Z
authors.lastname: Reiner
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000453:epidemiology* / Q000628:therapy*; D008297:Male; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D012955:Societies, Medical
chemical_list: D008078:Cholesterol, LDL