This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Academic Research Organization Hospital Israelita Albert Einstein Sao Paulo Brazil

Carbohydrate and Lipid Metabolism Research Unit Division of Endocrinology and Metabolism Department of Medicine Faculty of Health Sciences University of the Witwatersrand Parktown Johannesburg South Africa

Cardiovascular Center Osaka Medical and Pharmaceutical University Osaka Japan

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

Clinical Lipidology and Rare Lipid Disorders Unit Community Genomic Medicine Center Department of Medicine Université de Montréal ECOGENE Clinical and Translational Research Center and Lipid Clinic Chicoutimi Hospital Chicoutimi Québec Canada

Department of Biochemistry College of Medicine and Health Sciences Medical Research Center Sultan Qaboos University Muscat Oman

Department of Cardiology Faculty of Medicine Ege University Izmir Turkey

Department of Cardiology Hacettepe University Faculty of Medicine Ankara Turkey

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

Department of Internal Medicine Erasmus MC Medical Center Rotterdam The Netherlands

Department of Medicine and Robarts Research Institute Schulich School of Medicine and Dentistry Western University London Ontario Canada

Department of Pediatrics Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands

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

Department of Vascular Medicine Amsterdam Cardiovascular Sciences Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands

Division of Translational Medicine and Human Genetics Department of Medicine Perelman School of Medicine University of Pennsylvania 9017 Maloney Building 3600 Spruce Street Philadelphia PA 19104 USA

European Atherosclerosis Society Gothenburg Sweden

Imperial Centre for Cardiovascular Disease Prevention Department of Primary Care and Public Health School of Public Health Imperial College London London UK

IRCCS MultiMedica and Department of Pharmacological and Biomolecular Sciences Università degli Studi di Milano Milan Italy

Istituto di Biofisica Consiglio Nazionale delle Ricerche Genova Italy

Lipid Clinic Heart Institute University of São Paulo Medical School Hospital São Paulo Brazil

Medical School University of Western Australia and Department of Cardiology Lipid Disorders Clinic Royal Perth Hospital Perth Australia

Medizinische Klinik und Poliklinik 4 Ludwigs Maximilians University Klinikum Munich Germany

Pitié Salpêtrière Hospital and Sorbonne University Cardio metabolic Institute Paris France

Rogosin Institute Weill Cornell Medical College New York NY USA

Vascular Medicine and Metabolism Unit Research Unit on Lipids and Atherosclerosis Sant Joan University Hospital Universitat Rovira i Virgili IISPV CIBERDEM Reus Spain

Zobrazit více v PubMed

Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al. . Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146–2157. 10.1093/eurheartj/ehu274 PubMed DOI PMC

France M, Rees A, Datta D, Thompson G, Capps N, Ferns G, et al. . HEART UK statement on the management of homozygous familial hypercholesterolaemia in the United Kingdom. Atherosclerosis 2016;255:128–139. 10.1016/j.atherosclerosis.2016.10.017 PubMed DOI

Watts GF, Gidding S, Wierzbicki AS, Toth PP, Alonso R, Brown WV, et al. . Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Int J Cardiol 2014;171:309–325. 10.1016/j.ijcard.2013.11.025 PubMed DOI

Harada-Shiba M, Arai H, Ishigaki Y, Ishibashi S, Okamura T, Ogura M, et al. . Guidelines for diagnosis and treatment of familial hypercholesterolemia 2017. J Atheroscler Thromb 2018;25:751–770. 10.5551/jat.CR003 PubMed DOI PMC

Brunham LR, Ruel I, Aljenedil S, Riviere JB, Baass A, Tu JV, et al. . Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: update 2018. Can J Cardiol 2018;34:1553–1563. 10.1016/j.cjca.2018.09.005 PubMed DOI

Watts GF, Sullivan DR, Hare DL, Kostner KM, Horton AE, Bell DA, et al. . Integrated guidance for enhancing the care of familial hypercholesterolaemia in Australia. Heart Lung Circ 2021;30:324–349. 10.1016/j.hlc.2020.09.943 PubMed DOI

Groselj U, Wiegman A, Gidding SS. Screening in children for familial hypercholesterolaemia: start now. Eur Heart J 2022;43:3209–3212. 10.1093/eurheartj/ehac224 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;5:217–229. 10.1001/jamacardio.2019.5173 PubMed DOI

Vallejo-Vaz AJ, Kondapally Seshasai SR, Cole D, Hovingh GK, Kastelein JJ, Mata P, et al. . Familial hypercholesterolaemia: a global call to arms. Atherosclerosis 2015;243:257–259. 10.1016/j.atherosclerosis.2015.09.021 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;141:1742–1759. 10.1161/CIRCULATIONAHA.119.044795 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;75:2553–2566. 10.1016/j.jacc.2020.03.057 PubMed DOI

Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, et al. . Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study. Lancet 2022;399:719–728. 10.1016/S0140-6736(21)02001-8 PubMed DOI PMC

Sjouke B, Kusters DM, Kindt I, Besseling J, Defesche JC, Sijbrands EJ, et al. . Homozygous autosomal dominant hypercholesterolaemia in The Netherlands: prevalence, genotype-phenotype relationship, and clinical outcome. Eur Heart J 2015;36:560–565. 10.1093/eurheartj/ehu058 PubMed DOI

Bertolini S, Calandra S, Arca M, Averna M, Catapano AL, Tarugi P, et al. . Homozygous familial hypercholesterolemia in Italy: clinical and molecular features. Atherosclerosis 2020;312:72–78. 10.1016/j.atherosclerosis.2020.08.027 PubMed DOI

Salen G, von Bergmann K, Lutjohann D, Kwiterovich P, Kane J, Patel SB, et al. . Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 2004;109:966–971. 10.1161/01.CIR.0000116766.31036.03 PubMed DOI PMC

Kidambi S, Patel SB. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. J Clin Pathol 2008;61:588–594. 10.1136/jcp.2007.049775 PubMed DOI

Hansel B, Carrie A, Brun-Druc N, Leclert G, Chantepie S, Coiffard AS, et al. . Premature atherosclerosis is not systematic in phytosterolemic patients: severe hypercholesterolemia as a confounding factor in five subjects. Atherosclerosis 2014;234:162–168. 10.1016/j.atherosclerosis.2014.02.030 PubMed DOI

Hegele RA, Boren J, Ginsberg HN, Arca M, Averna M, Binder CJ, et al. . Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement. Lancet Diabetes Endocrinol 2020;8:50–67. 10.1016/S2213-8587(19)30264-5 PubMed DOI

Bjorkhem I. Cerebrotendinous xanthomatosis. Curr Opin Lipidol 2013;24:283–287. 10.1097/MOL.0b013e328362df13 PubMed DOI

Koyama S, Sekijima Y, Ogura M, Hori M, Matsuki K, Miida T, et al. . Cerebrotendinous xanthomatosis: molecular pathogenesis, clinical spectrum, diagnosis, and disease-modifying treatments. J Atheroscler Thromb 2021;28:905–925. 10.5551/jat.RV17055 PubMed DOI PMC

Berberich AJ, Hegele RA. The complex molecular genetics of familial hypercholesterolaemia. Nat Rev Cardiol 2019;16:9–20. 10.1038/s41569-018-0052-6 PubMed DOI

D'Erasmo L, Di Costanzo A, Arca M. Autosomal recessive hypercholesterolemia: update for 2020. Curr Opin Lipidol 2020;31:56–61. 10.1097/MOL.0000000000000664 PubMed DOI

Biesecker LG. Correspondence on: “homozygous familial hypercholesterolemia in Italy: clinical and molecular features”. Atherosclerosis 2021;326:63–64. 10.1016/j.atherosclerosis.2021.03.015 PubMed DOI

Defesche JC, Gidding SS, Harada-Shiba M, Hegele RA, Santos RD, Wierzbicki AS. Familial hypercholesterolaemia. Nat Rev Dis Primers 2017;3:17093. 10.1038/nrdp.2017.93 PubMed DOI

Brown EE, Sturm AC, Cuchel M, Braun LT, Duell PB, Underberg JA, et al. . Genetic testing in dyslipidemia: a scientific statement from the National Lipid Association. J Clin Lipidol 2020;14:398–413. 10.1016/j.jacl.2020.04.011 PubMed DOI

Chora JR, Iacocca MA, Tichy L, Wand H, Kurtz CL, Zimmermann H, et al. . The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification. Genet Med 2022;24:293–306. 10.1016/j.gim.2021.09.012 PubMed DOI

Belanger AM, Akioyamen L, Alothman L, Genest J. Evidence for improved survival with treatment of homozygous familial hypercholesterolemia. Curr Opin Lipidol 2020;31:176–181. 10.1097/MOL.0000000000000686 PubMed DOI

Lazarte J, Hegele RA. Editorial comment: hazards of interpreting genetic reports. Curr Opin Lipidol 2021;32:81–82. 10.1097/MOL.0000000000000738 PubMed DOI

Trinder M, Paquette M, Cermakova L, Ban MR, Hegele RA, Baass A, et al. . Polygenic contribution to low-density lipoprotein cholesterol levels and cardiovascular risk in monogenic familial hypercholesterolemia. Circ Genom Precis Med 2020;13:515–523. 10.1161/CIRCGEN.120.002919 PubMed DOI PMC

Wang J, Dron JS, Ban MR, Robinson JF, McIntyre AD, Alazzam M, et al. . Polygenic versus monogenic causes of hypercholesterolemia ascertained clinically. Arterioscler Thromb Vasc Biol 2016;36:2439–2445. 10.1161/ATVBAHA.116.308027 PubMed DOI

D'Erasmo L, Minicocci I, Di Costanzo A, Pigna G, Commodari D, Ceci F, et al. . Clinical implications of monogenic versus polygenic hypercholesterolemia: long-term response to treatment, coronary atherosclerosis burden, and cardiovascular events. J Am Heart Assoc 2021;10:e018932. 10.1161/JAHA.120.018932 PubMed DOI PMC

Brown EE. The genetic counselor's role in management of patients with dyslipidemia. Curr Opin Lipidol 2021;32:83–88. 10.1097/MOL.0000000000000732 PubMed DOI

Expert Panel on Integrated Guidelines for Cardiovascular Health, Risk Reduction in Children, Adolescents, National Heart Lung, Blood Institute . Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128:S213–S256. 10.1542/peds.2009-2107C PubMed DOI PMC

National Institute for Health and Care Excellence . Familial hypercholesterolaemia: identification and management. Updated 4 October 2019.https://www.nice.org.uk/guidance/cg71/chapter/Recommendations (14 August 2022, date last accessed). PubMed

Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. . Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015;36:2425–2437. 10.1093/eurheartj/ehv157 PubMed DOI PMC

Gidding SS, Wiegman A, Groselj U, Freiberger T, Peretti N, Dharmayat KI, et al. . Paediatric familial hypercholesterolaemia screening in Europe—public policy background and recommendations. Eur J Prev Cardiol 2022;29:2301–2311. 10.1093/eurjpc/zwac200 PubMed DOI

Klancar G, Groselj U, Kovac J, Bratanic N, Bratina N, Trebusak Podkrajsek K, et al. . Universal screening for familial hypercholesterolemia in children. J Am Coll Cardiol 2015;66:1250–1257. 10.1016/j.jacc.2015.07.017 PubMed DOI

Bedlington N, Abifadel M, Beger B, Bourbon M, Bueno H, Ceska R, et al. . The time is now: achieving FH paediatric screening across Europe—the Prague declaration. GMS Health Innov Technol 2022;16:Doc04. 10.3205/hta000136 PubMed DOI PMC

Ibarretxe D, Rodriguez-Borjabad C, Feliu A, Bilbao JA, Masana L, Plana N. Detecting familial hypercholesterolemia earlier in life by actively searching for affected children: the DECOPIN project. Atherosclerosis 2018;278:210–216. 10.1016/j.atherosclerosis.2018.09.039 PubMed DOI

Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. . Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022;43:3925–3946. 10.1093/eurheartj/ehac361 PubMed DOI PMC

Luirink IK, Kuipers IM, Hutten BA, Planken RN, Backx A, Groothoff JW, et al. . Coronary computed tomography angiography and echocardiography in children with homozygous familial hypercholesterolemia. Atherosclerosis 2019;285:87–92. 10.1016/j.atherosclerosis.2019.04.219 PubMed DOI

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. . 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–188. 10.1093/eurheartj/ehz455 PubMed DOI

Ray KK, Reeskamp LF, Laufs U, Banach M, Mach F, Tokgozoglu LS, et al. . Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J 2022;43:830–833. 10.1093/eurheartj/ehab718 PubMed DOI

Mohamed F, Seedat F, Raal FJ. Novel therapies for familial hypercholesterolemia. Curr Opin Endocrinol Diabetes Obes 2021;28:188–195. 10.1097/MED.0000000000000590 PubMed DOI

Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, et al. . Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:341–350. 10.1016/S0140-6736(14)61374-X PubMed DOI

Blom DJ, Harada-Shiba M, Rubba P, Gaudet D, Kastelein JJP, Charng MJ, et al. . Efficacy and safety of alirocumab in adults with homozygous familial hypercholesterolemia: the ODYSSEY HoFH trial. J Am Coll Cardiol 2020;76:131–142. 10.1016/j.jacc.2020.05.027 PubMed DOI

Santos RD, Stein EA, Hovingh GK, Blom DJ, Soran H, Watts GF, et al. . Long-term evolocumab in patients with familial hypercholesterolemia. J Am Coll Cardiol 2020;75:565–574. 10.1016/j.jacc.2019.12.020 PubMed DOI

Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, et al. . Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol 2017;5:280–290. 10.1016/S2213-8587(17)30044-X PubMed DOI

Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013;128:2113–2120. 10.1161/CIRCULATIONAHA.113.004678 PubMed DOI

Reijman MD, Kusters DM, Wiegman A. Advances in familial hypercholesterolaemia in children. Lancet Child Adolesc Health 2021;5:652–661. 10.1016/S2352-4642(21)00095-X PubMed DOI

Hussain MM, Rava P, Walsh M, Rana M, Iqbal J. Multiple functions of microsomal triglyceride transfer protein. Nutr Metab (Lond) 2012;9:14. 10.1186/1743-7075-9-14 PubMed DOI PMC

D'Erasmo L, Cefalu AB, Noto D, Giammanco A, Averna M, Pintus P, et al. . Efficacy of lomitapide in the treatment of familial homozygous hypercholesterolemia: results of a real-world clinical experience in Italy. Adv Ther 2017;34:1200–1210. 10.1007/s12325-017-0531-x PubMed DOI

Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, et al. . Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet 2013;381:40–46. 10.1016/S0140-6736(12)61731-0 PubMed DOI PMC

D'Erasmo L, Gallo A, Cefalu AB, Di Costanzo A, Saheb S, Giammanco A, et al. . Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey. Orphanet J Rare Dis 2021;16:381. 10.1186/s13023-021-01999-8 PubMed DOI PMC

D'Erasmo L, Steward K, Cefalu AB, Di Costanzo A, Boersma E, Bini S, et al. . Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study. Eur J Prev Cardiol 2022;29:832–841. 10.1093/eurjpc/zwab229 PubMed DOI

Blom DJ, Averna MR, Meagher EA, du Toit Theron H, Sirtori CR, Hegele RA, et al. . Long-term efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in patients with homozygous familial hypercholesterolemia. Circulation 2017;136:332–335. 10.1161/CIRCULATIONAHA.117.028208 PubMed DOI

Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, et al. . Evinacumab for homozygous familial hypercholesterolemia. N Engl J Med 2020;383:711–720. 10.1056/NEJMoa2004215 PubMed DOI

Gaudet D, Iannuzzo G, Stefanutti C, Stroes ES, Rosenson RS, Turner T, et al. . Long-term efficacy and safety of evinacumab in adult and adolescent patients with homozygous familial hypercholesterolemia. Circulation 2021;144:A12756.

Raal FJ, Reeskamp R, Kastelein JJ, Rubba P, Duell B, Koseki M, et al. . The long-term safety and efficacy of evinacumab in patients with homozygous familial hypercholesterolemia. Circulation 2021;144:A12066. 10.1161/circ.144.suppl_1.12066 DOI

Stefanutti C, Julius U, Watts GF, Harada-Shiba M, Cossu M, Schettler VJ, et al. . Toward an international consensus-integrating lipoprotein apheresis and new lipid-lowering drugs. J Clin Lipidol 2017;11:858–871.e3. 10.1016/j.jacl.2017.04.114 PubMed DOI

Alothman L, Belanger AM, Ruel I, Brunham LR, Hales L, Genest J, et al. . Health-related quality of life in homozygous familial hypercholesterolemia: a systematic review and meta-analysis. J Clin Lipidol 2022;16:52–65. 10.1016/j.jacl.2021.11.014 PubMed DOI

Kayikcioglu M, Tokgozoglu L, Yilmaz M, Kaynar L, Aktan M, Durmus RB, et al. . A nation-wide survey of patients with homozygous familial hypercholesterolemia phenotype undergoing LDL-apheresis in Turkey (A-HIT 1 registry). Atherosclerosis 2018;270:42–48. 10.1016/j.atherosclerosis.2018.01.034 PubMed DOI

Pottle A, Thompson G, Barbir M, Bayly G, Cegla J, Cramb R, et al. . Lipoprotein apheresis efficacy, challenges and outcomes: a descriptive analysis from the UK lipoprotein apheresis registry, 1989–2017. Atherosclerosis 2019;290:44–51. 10.1016/j.atherosclerosis.2019.09.006 PubMed DOI

Kroon AA, van't Hof MA, Demacker PN, Stalenhoef AF. The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels. Atherosclerosis 2000;152:519–526. 10.1016/S0021-9150(00)00371-3 PubMed DOI

Thompson GR, Barbir M, Davies D, Dobral P, Gesinde M, Livingston M, et al. . Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis 2010;208:317–321. 10.1016/j.atherosclerosis.2009.06.010 PubMed DOI

Ibrahim M, El-Hamamsy I, Barbir M, Yacoub MH. Translational lessons from a case of combined heart and liver transplantation for familial hypercholesterolemia 20 years post-operatively. J Cardiovasc Transl Res 2012;5:351–358. 10.1007/s12265-011-9311-1 PubMed DOI

El-Rassi I, Chehab G, Saliba Z, Alawe A, Jebara V. Fatal cardiac atherosclerosis in a child 10 years after liver transplantation: a case report and a review. J Clin Lipidol 2011;5:329–332. 10.1016/j.jacl.2011.05.002 PubMed DOI

Martinez M, Brodlie S, Griesemer A, Kato T, Harren P, Gordon B, et al. . Effects of liver transplantation on lipids and cardiovascular disease in children with homozygous familial hypercholesterolemia. Am J Cardiol 2016;118:504–510. 10.1016/j.amjcard.2016.05.042 PubMed DOI

Al Dubayee M, Kayikcioglu M, van Lennep JR, Hergli N, Mata P. Is liver transplant curative in homozygous familial hypercholesterolemia? A review of nine global cases. Adv Ther 2022;39:3042–3057. 10.1007/s12325-022-02131-3 PubMed DOI PMC

Ishigaki Y, Kawagishi N, Hasegawa Y, Sawada S, Katagiri H, Satomi S, et al. . Liver transplantation for homozygous familial hypercholesterolemia. J Atheroscler Thromb 2019;26:121–127. 10.5551/jat.RV17029 PubMed DOI PMC

Cephus CE, Qureshi AM, Sexson Tejtel SK, Alam M, Moodie DS. Coronary artery disease in a child with homozygous familial hypercholesterolemia: regression after liver transplantation. J Clin Lipidol 2019;13:880–886. 10.1016/j.jacl.2019.09.007 PubMed DOI

Schmidt HH, Tietge UJ, Buettner J, Barg-Hock H, Offner G, Schweitzer S, et al. . Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation. Clin Transplant 2008;22:180–184. 10.1111/j.1399-0012.2007.00764.x PubMed DOI

Revell SP, Noble-Jamieson G, Johnston P, Rasmussen A, Jamieson N, Barnes ND. Liver transplantation for homozygous familial hypercholesterolaemia. Arch Dis Child 1995;73:456–458. 10.1136/adc.73.5.456 PubMed DOI PMC

Greco M, Robinson JD, Eltayeb O, Benuck I. Progressive aortic stenosis in homozygous familial hypercholesterolemia after liver transplant. Pediatrics 2016;138:e20160740. 10.1542/peds.2016-0740 PubMed DOI

Bajaj A, Cuchel M. Advancements in the treatment of homozygous familial hypercholesterolemia. J Atheroscler Thromb 2022;29:1125–1135. 10.5551/jat.RV17065 PubMed DOI PMC

Cesaro A, Fimiani F, Gragnano F, Moscarella E, Schiavo A, Vergara A, et al. . New frontiers in the treatment of homozygous familial hypercholesterolemia. Heart Fail Clin 2022;18:177–188. 10.1016/j.hfc.2021.07.008 PubMed DOI

Chadwick AC, Evitt NH, Lv W, Musunuru K. Reduced blood lipid levels with in vivo CRISPR-Cas9 base editing of ANGPTL3. Circulation 2018;137:975–977. 10.1161/CIRCULATIONAHA.117.031335 PubMed DOI PMC

Musunuru K, Chadwick AC, Mizoguchi T, Garcia SP, DeNizio JE, Reiss CW, et al. . In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 2021;593:429–434. 10.1038/s41586-021-03534-y PubMed DOI

Verve Therapeutics 2022. https://ir.vervetx.com/news-releases/news-release-details/verve-therapeutics-provides-regulatory-update-verve-101 (22 December 2022, date last accessed).

Amundsen AL, Khoury J, Iversen PO, Bergei C, Ose L, Tonstad S, et al. . Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia. Atherosclerosis 2006;189:451–457. 10.1016/j.atherosclerosis.2006.01.002 PubMed DOI

Ogura M, Makino H, Kamiya C, Yoshimatsu J, Soran H, Eatough R, et al. . Lipoprotein apheresis is essential for managing pregnancies in patients with homozygous familial hypercholesterolemia: seven case series and discussion. Atherosclerosis 2016;254:179–183. 10.1016/j.atherosclerosis.2016.10.018 PubMed DOI

Russi G. Severe dyslipidemia in pregnancy: the role of therapeutic apheresis. Transfus Apher Sci 2015;53:283–287. 10.1016/j.transci.2015.11.008 PubMed DOI

Graham DF, Raal FJ. Management of familial hypercholesterolemia in pregnancy. Curr Opin Lipidol 2021;32:370–377. 10.1097/MOL.0000000000000790 PubMed DOI

US Food and Drug Administration . Drug Safety Communication 7-20-2021. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. 2021.https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy#:∼:text=Statins%20are%20safe%20to%20prescribe%20in%20patients%20who%20are%20not,not%20generally%20necessary%20during%20pregnancy (14 August 2022, date last accessed).

Bruckert E, Saheb S, Bonte JR, Coudray-Omnes C. Daily life, experience and needs of persons suffering from homozygous familial hypercholesterolaemia: insights from a patient survey. Atheroscler Suppl 2014;15:46–51. 10.1016/j.atherosclerosissup.2014.07.006 PubMed DOI

Kayikcioglu M, Kuman-Tuncel O, Pirildar S, Yilmaz M, Kaynar L, Aktan M, et al. . Clinical management, psychosocial characteristics, and quality of life in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis in Turkey: results of a nationwide survey (A-HIT1 registry). J Clin Lipidol 2019;13:455–467. 10.1016/j.jacl.2019.02.001 PubMed DOI

Mulder J, Kranenburg LW, Treling WJ, Hovingh GK, Rutten JHW, Busschbach JJ, et al. . Quality of life and coping in Dutch homozygous familial hypercholesterolemia patients: a qualitative study. Atherosclerosis 2022;348:75–81. 10.1016/j.atherosclerosis.2022.03.015 PubMed DOI

Cesaro A, Gragnano F, Fimiani F, Moscarella E, Diana V, Pariggiano I, et al. . Impact of PCSK9 inhibitors on the quality of life of patients at high cardiovascular risk. Eur J Prev Cardiol 2020;27:556–558. 10.1177/2047487319839179 PubMed DOI

Alieva AS, Tokgozoglu L, Ray KK, Catapano AL. Lipid clinics network. Rationale and design of the EAS global project. Atheroscler Suppl 2020;42:e6–e8. 10.1016/j.atherosclerosissup.2021.01.002 PubMed DOI

Sarkies MN, Jones LK, Gidding SS, Watts GF. Improving clinical practice guidelines with implementation science. Nat Rev Cardiol 2022;19:3–4. 10.1038/s41569-021-00645-x PubMed DOI

Watts GF, Gidding SS, Mata P, Pang J, Sullivan DR, Yamashita S, et al. . Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care. Nat Rev Cardiol 2020;17:360–377. 10.1038/s41569-019-0325-8 PubMed DOI

Tada H, Kurashina T, Ogura M, Takegami M, Miyamoto Y, Arai H, et al. . Prospective Registry Study of Primary Dyslipidemia (PROLIPID): rationale and study design. J Atheroscler Thromb 2022;29:953–969. 10.5551/jat.63222 PubMed DOI PMC

LDLR gene rearrangements in Czech FH patients likely arise from one mutational event