Author + information
- Received February 12, 2018
- Revision received May 11, 2018
- Accepted May 15, 2018
- Published online July 30, 2018.
- Amy C. Sturm, MSa,∗∗ (, )@AmyCurrySturm@Penn@GeisingerHealth@PennMedicine,
- Joshua W. Knowles, MD, PhDb,c,∗,
- Samuel S. Gidding, MDd,∗,
- Zahid S. Ahmad, MDe,
- Catherine D. Ahmed, MBAc,
- Christie M. Ballantyne, MDf,
- Seth J. Baum, MDc,g,
- Mafalda Bourbon, PhDh,i,
- Alain Carrié, MD, PhDj,
- Marina Cuchel, MD, PhDk,
- Sarah D. de Ferranti, MD, MPHl,
- Joep C. Defesche, PhDm,
- Tomas Freiberger, MD, PhDn,o,
- Ray E. Hershberger, MDp,
- G. Kees Hovingh, MD, PhDq,
- Lala Karayan, MPHc,
- Johannes Jacob Pieter Kastelein, MD, PhDq,
- Iris Kindt, MD, MPHc,
- Stacey R. Lane, JD, MBEc,
- Sarah E. Leigh, MSc, PhDr,
- MacRae F. Linton, MDs,
- Pedro Mata, MD, PhDt,
- William A. Neal, MDc,u,
- Børge G. Nordestgaard, MD, DMScv,w,
- Raul D. Santos, MD, PhDx,
- Mariko Harada-Shiba, MD, PhDy,
- Eric J. Sijbrands, MD, PhDz,
- Nathan O. Stitziel, MD, PhDaa,
- Shizuya Yamashita, MD, PhDbb,cc,
- Katherine A. Wilemon, BSc,†,
- David H. Ledbetter, PhDa,†,
- Daniel J. Rader, MDc,dd,†,
- Convened by the Familial Hypercholesterolemia Foundation
- aGenomic Medicine Institute, Geisinger, Danville, Pennsylvania
- bDepartment of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University, Stanford California
- cThe Familial Hypercholesterolemia Foundation, Pasadena, California
- dNemours Cardiac Center, A.I. DuPont Hospital for Children, Wilmington, Delaware
- eDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- fDepartment of Medicine, Baylor College of Medicine, Houston, Texas
- gDepartment of Integrated Medical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida
- hUnidade I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal
- iUniversity of Lisboa, Faculty of Sciences, BioISI–Biosystems & Integrative Sciences Institute, Lisboa, Portugal
- jSorbonne Université and Centre de Génétique Moléculaire et Chromosomique, unité de Génétique de l’Obésitéet des dyslipidémies, Hôpital de la Pitié-Salpêtrière, Paris, France
- kDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
- lDepartment of Cardiology, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts
- mDepartment of Clinical Genetics, Academic Medical Center at the University of Amsterdam, Amsterdam, the Netherlands
- nCentral European Institute of Technology, Masaryk University, Brno, Czech Republic
- oCentre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic
- pDepartment of Internal Medicine, Wexner Medical Center at The Ohio State University, Columbus, Ohio
- qDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
- rBioinformatics, Genomics England, Queen Mary University of London, London, United Kingdom
- sMedicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee
- tFundación Hipercolesterolemia Familiar, Madrid, Spain
- uDepartment of Pediatrics (Cardiology), West Virginia University, Morgantown, West Virginia
- vDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
- wDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- xLipid Clinic Heart Institute (InCor) University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil
- yDepartment of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
- zDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
- aaDepartment of Medicine, Division of Cardiology, Department of Genetics, McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri
- bbDepartment of Cardiovascular Medicine, Rinku General Medical Center, Osaka, Japan
- ccDepartments of Community Medicine and Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- ddDepartments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
- ↵∗Address for correspondence:
Ms. Amy C. Sturm, Genomic Medicine Institute, 100 North Academy Avenue, Danville, Pennsylvania 17822-2620.
Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
↵∗ Ms. Sturm, Dr. Knowles, and Dr. Gidding contributed equally as first authors.
↵† Ms. Wilemon, Dr. Ledbetter, and Dr. Rader contributed equally as last authors.
Ms. Sturm has served on scientific advisory boards for Clear Genetics and Genome Medical. Dr. Knowles has served as the chief medical advisor for the Familial Hypercholesterolemia Foundation; and has received funding from an American Heart Association National Innovative Research Award and the Doris Duke Charitable Trust. Dr. Gidding has served as a consultant for Regenxbio. Dr. Ahmad has performed research for the National Institutes of Health and Regeneron; has served as a speaker for Amgen, Sanofi, and Akcea; and has served on advisory boards for Sanofi and Akcea. Dr. Ballantyne has received grant/research support (all paid to institution, not individual) from Abbott Diagnostic, Amarin, Amgen, Esperion, Ionis, Novartis, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo; and has served as a consultant for Abbott Diagnostics, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esperion, Ionis, Matinas BioPharma Inc., Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr. Baum has served on scientific advisory boards, provided consulting, and performed clinical research for Amgen, Sanofi/Regeneron, Esperion, Akcea, AstraZeneca, Boehringer Ingelheim/Lilly, Novo Nordisk, and Gemphire; and has served as a speaker for Amgen, Boehringer Ingelheim/Lilly, Novo Nordisk, and Aralez. Dr. Bourbon has received research funding from Praxis (Aegerion), Alexion, Regeneron, and Gendiag. Dr. Carrie has received honoraria from Amgen SAS and Alexion Pharma France SAS; and a grant from Alexion Pharma France SAS. Dr. Cuchel has received industry support for the performance of clinical trials from Akcea, Regeneron Pharmaceuticals, and Regenxbio; has served on the speakers bureau for Aegerion Pharmaceuticals; and has received federal funding from the National Heart, Lung, and Blood Institute (HL059407). Dr. de Ferranti has received royalties from UpToDate for topics related to pediatric lipid screening and treatment; and grant funding from the Pediatric Heart Network (no overlap) and the New England Congenital Cardiology Research Foundation (no overlap). Dr. Freiberger has received grants from the Ministry of Health of the Czech Republic (16-29084A and 15-28277A) (all rights reserved). Dr. Hovingh has served as an advisory board member and/or speaker for Pfizer, Regeneron, Sanofi, Amgen, and Aegerion (his institution receives the financial compensation for these services). Dr. Kastelein has provided consulting for Sanofi, Affiris, Akarna Therapeutics, Amgen, CSL Behring, Regeneron, Staten Biotech, Madrigal, The Medicines Company, Kowa, Lilly, Esperion, Gemphire, Ionis Pharmaceuticals, and Akcea Pharmaceuticals. Dr. Linton has performed research for Merck, Amgen, Sanofi, Regeneron, Genzyme, Ionis, the National Institutes of Health (HL116263), FH Foundation CASCADE; and has served as a consultant for Regenxbio. Dr. Mata has received honoraria for advisory boards and research grants from Amgen and Sanofi. Dr. Santos has received honoraria related to consulting, speaker activities, and research from Amgen, AstraZeneca, Akcea, Biolab, Esperion, Merck, Novo Nordisk, Pfizer, and Sanofi/Regeneron. Dr. Harada-Shiba has received grants from Japan Agency for Medical Research and Development, Japanese Ministry of Health, Labour and Welfare, The Japanese Circulation Society, Aegerion, Astellas Pharm, Takeda, MSD, and Kaneka Medics; and has received honoraria for talks from Astellas, Astellas Amgen, Sanofi, Takeda, MSD, Boeringer Ingelheim, Daiichi-Sankyo, Kaneka Medics, and Kowa. Dr. Sijbrands received a grant from Amgen for scientific research (not drug related). Dr. Yamashita has received research grants from Merck Sharp & Dohme, Bayer, Boehringer Ingelheim, Takeda, Ono, and Astellas; has received consulting fees from Skylight Biotec; and has served on the speakers bureau for Kowa, Merck Sharp & Dohme, Astellas, Astellas-Amgen Biopharma, and Sanofi. Ms. Wilemon has served as the chief executive officer for the Familial Hypercholesterolemia Foundation. Dr. Ledbetter has served as the chief scientific officer for Clear Genetics, Inc. Dr. Rader has served as the chief scientific advisor for the Familial Hypercholesterolemia Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 12, 2018.
- Revision received May 11, 2018.
- Accepted May 15, 2018.
- 2018 American College of Cardiology Foundation
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