Data from the Global HoFH International Clinical Collaborators (HICC) registry, which has now included over 950 patients with homozygous familial hypercholesterolaemia (HoFH) from 45 countries. HoFH is characterised by extremely elevated LDL cholesterol from birth and very high risk of premature atherosclerotic CVD. Median age at diagnosis was 12 years (IQR 5.5-27.0), with untreated LDL cholesterol at median 14.7 mmol/L. At diagnosis 9% already had ASCVD or (supra)aortic valve disease; despite widespread lipid-lowering therapy, only 4% reached guideline LDL goals. Early initiation of lipoprotein apheresis was associated with greater LDL reductions and delayed ASCVD onset. Median age at death is just 37 years [20-50]. No sex differences emerged at diagnosis or in treatment, and the usual sex gap in CVD onset is absent. Global disparities in genetic screening and access to therapy are profound, with earlier events in low-income countries.
Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder marked by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels from birth and a very high risk of premature atherosclerotic cardiovascular disease (ASCVD). To address the global paucity of observational data, the HoFH International Clinical Collaborators (HICC) registry (NCT04815005) was established. To date, over 950 HoFH individuals from 45 countries have been included. The median age at diagnosis was 12 years (IQR: 5.5-27.0), and untreated LDL-C levels were markedly elevated [median 14.7 mmol/L (11.6-18.4)]. At diagnosis, 9% had ASCVD or (supra)aortic valve disease, and despite the widespread use of lipid-lowering therapy (LLT), only 4% achieved guideline-recommended LDL-C goals. Early initiation of lipoprotein-apheresis was associated with greater LDL-C reductions and delayed ASCVD onset. Cardiovascular burden remains substantial, with a median age at death of 37 years [20-50]. No sex differences were observed in age or clinical characteristics at diagnosis, treatment patterns, or timing of ASCVD, although the usual sex gap in cardiovascular disease onset was absent. Profound global disparities persist, including limited genetic screening, restricted access to LLT, and earlier onset of major adverse cardiovascular events in non-high-income countries. Reproductive care for women remains highly variable and understudied. The HICC aims to guide global stakeholders in improving clinical outcomes for individuals with HoFH through earlier diagnosis, equitable access to advanced therapies, and broader inclusion of underserved regions. By generating evidence from routine clinical care and patient-reported data, identifying gaps in care, and fostering international collaboration, HICC seeks to advance a more equitable and effective global approach to HoFH management.
