Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 6;398(10312):1713-1725.
doi: 10.1016/S0140-6736(21)01122-3. Epub 2021 Sep 7.

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
Collaborators

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Lancet. .

Abstract

Background: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.

Methods: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.

Findings: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3-58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5-56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32-6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20-5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001).

Interpretation: Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia.

Funding: Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests CAA-S reports grants from Amgen, during the conduct of the study. FAl reports grants from National Science, Technology and Innovation Plan (MAARIFAH) of Saudi Arabia (08-BIO34-10), during the conduct of the study; and personal fees from Amgen, Amryt Pharma, and Algorithma Pharma, outside the submitted work. RA reports personal fees and non-financial support from Tecnofarma, and personal fees from Novo Nordisk, Abbott, Saval, and Teva, outside the submitted work. KA-R reports personal fees from Sanofi and Abbott, outside the submitted work. NA-S reports personal fees from Sanofi, Amgen, Merck, and AstraZeneca, outside the submitted work. MBa reports grants, personal fees, non-financial support, and other support from Akcea, Amgen, Daiichi Sankyo, Esperion, Freia Pharmaceuticals, Herbapol, Kogen, KRKA, Mylan, Novartis, Novo Nordisk, Polfarmex, Polpharma, Resverlogix, Sanofi–Regeneron, Servier, Teva, Valeant, and Zentiva, during the conduct of the study. SB reports grants from Agence Nationale de la Recherche, Amgen, and Sanofi, during the conduct of the study. CJB reports grants from Amgen, Sanofi, and Alexion, during the conduct of the study; and personal fees from Akcea, Novartis, and Amgen, outside the submitted work. MPB reports personal fees from Amgen and Sanofi, outside the submitted work. MBo reports grants from the Science and Technology Foundation (Portugal) and Akcea, both during the conduct of the study and outside the submitted work. ALC has received honoraria, lecture fees, or research grants from Akcea, Amgen, AstraZeneca, Eli Lilly, Genzyme, Kowa, Mediolanum, Menarini, Merck, Pfizer, Recordati, Sanofi, Sigma Tau, Medco, and Amryt outside the submitted work. PC reports grants and personal fees from Amgen, and personal fees from PTC Therapeutics, Novartis, and AstraZeneca, outside the submitted work. OSD reports grants and personal fees from Amgen and Sanofi, and personal fees from Merck Sharp & Dohme, Daiichi Sankyo, and Novartis, outside the submitted work. KID reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study; and personal fees from Bayer, outside the submitted work. TF reports grants from the Ministry of Health of the Czech Republic, during the conduct of the study; and personal fees from Novartis, Sanofi, and Amgen, outside the submitted work. JG reports grants from the Canadian Institutes of Health Research, during the conduct of the study. AT-H reports personal fees from AstraZeneca, Sanofi, Regeneron, Akcea, Novartis, Silence Therapeutics, and Draupnir Bio, outside the submitted work. MH-S reports grants from the Japanese Ministry of Health, Labour and Welfare, the Japanese Circulation Society, Takeda, Kaneka Medics, and Aegerion; grants and personal fees from Astellas Pharm, Merck Sharp & Dohme, Recordati, and Sanofi; and personal fees from Kowa, Daiichi Sankyo, and Mochida, outside the submitted work. KBH reports grants from Mills and Tine, grants and personal fees from Amgen, and personal fees from Sanofi, outside the submitted work. GKH reports grants from Kowa Research Europe, during the conduct of the study; research grants from the Netherlands Organization for Scientific Research (VIDI), Klinkerpad fonds, and the EU; institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker's bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron Pharmaceuticals; and part-time employment by Novo Nordisk. MK reports personal fees from Abbott, Actelion, AstraZeneca, Abdi Ibrahim, Aegerion, Bayer Schering, Menarini, and Sanofi Genzyme; grants and personal fees from Pfizer; and grants from Aegerion, Amyrt Pharma, Amgen, and Sanofi, outside the submitted work. WK reports grants from the Royal College of Physicians of Thailand and the Endocrine Society of Thailand, during the conduct of the study; and grants and other support from Amgen, outside the submitted work. GL reports grants, personal fees, and non-financial support from the Latvian National Research Program Biomedicine for Public Health 2014–17, the Ministry of Education and Science of the Republic of Latvia, and the Latvian Science Council (lzp-2020/1-0151), and personal fees and non-financial support from Amgen, Pfizer, AstraZeneca, Servier, Sanofi, Mylan, Novartis, Merck Sharp & Dohme, KRKA, and Zentiva, during the conduct of the study; personal fees and non-financial support from Bayer, Boehringer Ingelheim, Grindex, Abbott Laboratories, Siemens Laboratories, and Novo Nordisk, and non-financial support from Medtronic, outside the submitted work. EL reports personal fees and non-financial support from the Hellenic Atherosclerosis Society, during the conduct of the study; and personal fees from Amgen, Novartis, Mylan, and Servier, outside the submitted work. ARML reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study. ADM reports funding support for genotyping from the Medical Research Council of South Africa. WM reports grants from Siemens Healthineers, AstraZeneca, Bayer Vital, Bestbion, Boehringer Ingelheim, Immundiagnostik, Merck Chemicals, and Olink Proteomics; grants and personal fees from Aegerion Pharmaceuticals, Amgen, Sanofi, Amryt Pharmaceuticals, BASF, Abbott Diagnostics, Numares, Berlin-Chemie, Akzea Therapeutics, and Novartis Pharma; personal fees from Vifor Pharma; and other support from SYNLAB Holding Deutschland, outside the submitted work. HN reports grants from the Malaysian Ministry of Higher Education, FH-10 countries, University of Western Australia–Familial Hypercholesterolaemia Australasian Network–Asian-Pacific Society of Atherosclerosis and Vascular Disease, and BioEazy; and non-financial support from the European Atherosclerosis Society, during the conduct of the study. BGN reports personal fees from AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Kowa, Denka Seiken, Amarin, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics, outside the submitted work. FJR reports personal fees from Amgen, Sanofi–Aventis, Regeneron, and Novartis, outside the submitted work. KKR reports grants and personal fees from Amgen, Sanofi–Regeneron, Pfizer, Merck Sharp & Dohme, and Daiichi Sankyo; and personal fees from AstraZeneca, The Medicines Company, Kowa, Novartis, Lilly, Algorithm, Boehringer Ingelheim, AbbVie, Silence Therapeutics, Bayer, Esperion, Abbott, New Amsterdam, and Resverlogix, outside the submitted work. ŽR reports personal fees from Sanofi and Novartis, outside the submitted work. RDS reports grants and personal fees from Abbott, Amgen, AstraZeneca, Akcea, Biolab, Esperion, EMS, Kowa, Libbs, GETZ Pharma, Merck Sharp & Dohme, Merck, Novartis, Novo Nordisk, PTC Therapeutics, Pfizer, and Sanofi–Regeneron, outside the submitted work. HSc reports personal fees from Merck Sharp & Dohme, Amgen, Bayer Vital, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Servier, Brahms, Bristol Myers Squibb, Medtronic, Sanofi–Aventis, Synlab, AstraZeneca, Pfizer, and Vifor, outside the submitted work. CATS reports grants from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study. ES reports personal fees from Amgen, Sanofi–Regeneron, Esperion, Novartis, and Novo Nordisk, outside the submitted work. AVS reports lecturer honoraria from AstraZeneca, Abbott, KRKA, Teva Pharmaceuticals, Sanofi, Amgen, Servier, Akrichin, and Janssen. MT reports personal fees from Sanofi, outside the submitted work. LT reports personal fees from Abbott, Amgen, Mylan, Sanofi, Novartis, Recordati, Daiichi Sankyo, and Pfizer, outside the submitted work. BT reports personal fees from Amgen, Kowa, and Merck Serono, outside the submitted work. ADT reports grants from AstraZeneca and Epsilon Health, and grants and personal fees from Elpen, Libytec, and Galenica, outside the submitted work. AJVV reports participation in research grants to the European Atherosclerosis Society–Imperial College London from Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron, during the conduct of the study; and personal fees for consulting from Bayer and honoraria for lectures from Amgen, Mylan, and Akcea, outside the submitted work. GFW reports grants and personal fees from Amgen, Regeneron, Sanofi, Novartis, and Arrowhead; and personal fees from AstraZeneca, Kowa, and Esperion, outside the submitted work. SY reports personal fees from Kowa, Merck Sharp & Dohme, Skylight Biotec, Hayashibara, and Recordati Rare Diseases Japan, outside the submitted work. All other authors declare no competing interests.

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

Substances