J 2022

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

TROMP, Tycho R, Merel L. HARTGERS, G Kees HOVINGH, Antonio J. VALLEJO-VAZ, Kausik K. RAY et. al.

Basic information

Original name

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Authors

TROMP, Tycho R, Merel L. HARTGERS, G Kees HOVINGH, Antonio J. VALLEJO-VAZ, Kausik K. RAY, Handrean SORAN, Tomáš FREIBERGER (203 Czech Republic, belonging to the institution), Stefano BERTOLINI, Mariko HARADA-SHIBA, Dirk J. BLOM, Frederick J. RAAL and Marina CUCHEL (guarantor)

Edition

Lancet, New York, Elsevier Science Inc. 2022, 0140-6736

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30218 General and internal medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 168.900

RIV identification code

RIV/00216224:14110/22:00126417

Organization unit

Faculty of Medicine

DOI

UT WoS

000758794200019

Keywords in English

homozygous familial hypercholesterolaemia

Tags

Tags

International impact, Reviewed
Změněno: 11/8/2022 12:52, Mgr. Tereza Miškechová

Abstract

V originále

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-highincome countries (9.3 mmol/ L, 6.7-12.7), with greater use of three or more lipid-lowering therapies (LLT; highincome 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. Copyright (C) 2022 Published by Elsevier Ltd. All rights reserved.