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
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AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary. CONCLUSION: This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
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Even with strict adherence, diet has limited impact on the severity of hypercholesterolemia in high-risk patients with severe hypercholesterolemia.
“however, even with strict adherence, diet has limited impact on the severity of hypercholesterolemia in this high-risk patient population (28).”
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- Authors
- Cuchel, M., Bruckert, E., Ginsberg, H. N., Raal, F. J., Santos, R. D., Hegele, R. A., Kuivenhoven, J. A., Nordestgaard, B. G., Descamps, O. S., Steinhagen-Thiessen, E., Tybjaerg-Hansen, A., Watts, G. F., Averna, M., Boileau, C., Boren, J., Catapano, A. L., Defesche, J. C., Hovingh, G. K., Humphries, S. E., Kovanen, P. T., Masana, L., Pajukanta, P., Parhofer, K. G., Ray, K. K., Stalenhoef, A. F. H., Stroes, E., Taskinen, M.-R., Wiegman, A., Wiklund, O., Chapman, M. J., for the European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia, Cuchel, M., Bruckert, E., Chapman, M. J., Descamps, O. S., Ginsberg, H. N., Hegele, R. A., Kuivenhoven, J. A., Nordestgaard, B. G., Raal, F. J., Santos, R. D., Steinhagen-Thiessen, E., Tybjaerg-Hansen, A., Watts, G. F., Chapman, M. J., Ginsberg, H. N., Averna, M., Boileau, C., Boren, J., Catapano, A. L., Defesche, J. C., Hovingh, G. K., Humphries, S. E., Kovanen, P. T., Masana, L., Pajukanta, P., Parhofer, K. G., Ray, K. K., Stalenhoef, A. F. H., Stroes, E., Taskinen, M.-R., Wiegman, A., & Wiklund, O.
- Affiliations
- University of Pennsylvania (US)
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-07-22
- Volume
- 35
- Issue
- 32
- Pages
- 2146-2157
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC4139706
- OpenAlex
- W2165791625
- Cited by
- 1,057
- References
- 84
- Citations by year
- 2026: 56 · 2025: 58 · 2024: 74 · 2023: 84 · 2022: 103 · 2021: 100 · 2020: 97 · 2019: 89 · 2018: 90 · 2017: 114 · 2016: 97 · 2015: 73 · 2014: 19 · 2013: 2
- FWCI
- 100.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- European Heart Journal (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Rovira & Virgili repository (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc)
- Radboud Repository (Radboud University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Heart and Stroke Foundation of Canada
- F. Hoffmann-La Roche
- Danone
- Genome Canada
- Regeneron Pharmaceuticals
- Valeant Pharmaceuticals International
- Università degli Studi di Milano
- Ontario Genomics
- Kowa Company
- Ontario Genomics Institute
- British Heart Foundation (RG/08/008/25291)
- University College London
- Institut National de la Santé et de la Recherche Médicale
- Gentofte Hospital
- Università degli Studi di Palermo
- Rigshospitalet
- Universidade de São Paulo
- Sahlgrenska Universitetssjukhuset
- Göteborgs Universitet
- Radboud Universitair Medisch Centrum
- Novo Nordisk Fonden (NNF13OC0004973)
- University of California, Los Angeles
- Canadian Institutes of Health Research (79523_1, MOP13430)
- National Heart, Lung, and Blood Institute (R01HL095056, P01HL028481)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- homozygous familial hypercholesterolemia, LDL cholesterol, atherosclerotic cardiovascular disease, early diagnosis, genetic testing, xanthoma, statin therapy, ezetimibe, lipoprotein apheresis, lomitapide, mipomersen, lipid-lowering therapy, cardiovascular follow-up, clinical management
- MeSH terms
- Anticholesteremic Agents, Arcus Senilis, Blood Component Removal, Cardiovascular Diseases, Diagnosis, Differential, Gene Frequency, Homozygote, Humans, Hyperlipoproteinemia Type II, Cholesterol, LDL, Mutation, Pedigree, Phenotype, Xanthomatosis, Liver Transplantation, Practice Guidelines as Topic, Genetic Heterogeneity, Early Diagnosis, Atherosclerosis
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