TY - JOUR
T1 - Worldwide experience of homozygous familial hypercholesterolaemia
T2 - retrospective cohort study
AU - Homozygous Familial Hypercholesterolaemia International Clinical Collaborators
AU - Tromp, Tycho R.
AU - Hartgers, Merel L.
AU - Hovingh, G. Kees
AU - Vallejo-Vaz, Antonio J.
AU - Ray, Kausik K.
AU - Soran, Handrean
AU - Freiberger, Tomas
AU - Bertolini, Stefano
AU - Harada-Shiba, Mariko
AU - Blom, Dirk J.
AU - Raal, Frederick J.
AU - Cuchel, Marina
AU - Tromp, Tycho R.
AU - Hartgers, Merel L.
AU - Hovingh, G. Kees
AU - Vallejo-Vaz, Antonio J.
AU - Ray, Kausik K.
AU - Bertolini, Stefano A.
AU - Pang, Jing
AU - Watts, Gerald F.
AU - Greber-Platzer, Susanne
AU - Mäser, Martin
AU - Stulnig, Thomas M.
AU - Ebenbichler, Christoph F.
AU - Bin Thani, Khalid
AU - Cassiman, David
AU - Descamps, Olivier S.
AU - Rymen, Daisy
AU - Witters, Peter
AU - Santos, Raul D.
AU - Brunham, Liam R.
AU - Francis, Gordon A.
AU - Genest, Jacques
AU - Hegele, Robert A.
AU - Kennedy, Brooke A.
AU - Ruel, Isabelle
AU - Sherman, Mark H.
AU - Jiang, Long
AU - Wang, Luya
AU - Reiner, Željko
AU - Blaha, Vladimir
AU - Ceska, Richard
AU - Dvorakova, Jana
AU - Dlouhy, Lubomir
AU - Horak, Pavel
AU - Soska, Vladimir
AU - Tichy, Lukas
AU - Urbanek, Robin
AU - Vaverkova, Helena
AU - Nemer, Georges
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/2/19
Y1 - 2022/2/19
N2 - Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.
AB - Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.
UR - http://www.scopus.com/inward/record.url?scp=85124623985&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(21)02001-8
DO - 10.1016/S0140-6736(21)02001-8
M3 - Article
C2 - 35101175
AN - SCOPUS:85124623985
SN - 0140-6736
VL - 399
SP - 719
EP - 728
JO - The Lancet
JF - The Lancet
IS - 10326
ER -