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Homozygous Familial Hypercholesterolemia in Canada: An Observational Study
Leslie Brown1, Isabelle Ruel1, Alexis Baass1
1Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Québec, Canada.
Insights
This study tracked 48 Canadian patients with homozygous familial hypercholesterolemia (HoFH), revealing significant cardiovascular events and aortic stenosis despite intensive lipid-lowering therapies. The findings highlight the ongoing challenges in managing this rare genetic condition.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Endocrinology
Background:
- Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder causing extremely high low-density lipoprotein cholesterol (LDL-C) levels.
- Untreated HoFH leads to severe xanthomas and premature atherosclerosis, significantly impacting patient lifespan.
- Effective lipid-lowering therapies have improved life expectancy for HoFH patients.
Purpose of the Study:
- To establish a comprehensive registry of HoFH patients in Canada.
- To characterize the clinical features and long-term cardiovascular outcomes within this population.
- To investigate the impact of founder effect regions on HoFH prevalence and characteristics.
Main Methods:
- Data collection through a standardized questionnaire administered to academic sites within the Familial Hypercholesterolemia Canada network.
- Inclusion of both clinical and genetic information from enrolled HoFH patients.
- Longitudinal follow-up to assess disease progression and treatment efficacy over time.
Main Results:
- A registry of 48 HoFH patients was established, with a median age at diagnosis of 12 years and high baseline LDL-C levels (15.0 mmol/L).
- At follow-up (median age 40 years), treated LDL-C levels decreased to 6.75 mmol/L with extensive use of statins, ezetimibe, PCSK9 inhibitors, and other advanced therapies.
- Despite treatment, 14.6% experienced major adverse cardiovascular events (average onset at 30 years), and 47.9% had aortic stenosis, with 20.8% undergoing aortic valve replacement. Mortality was 14.5%.
Conclusions:
- The Canadian HoFH patient registry provides critical insights into phenotypic variability and cardiovascular risk factors.
- Findings underscore the need for continued monitoring and advanced treatment strategies for HoFH.
- This registry will inform future research on quality of life and healthcare system burden associated with HoFH.
Background:
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients present with extensive xanthomas and premature atherosclerosis. Lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy of patients with HoFH.
Objectives:
The aim of the study was to obtain a comprehensive registry of HoFH in Canada, known to have several founder effect regions, and describe the clinical characteristics and cardiovascular outcomes of this population over time.
Methods:
Clinical and genetic data on patients with HoFH were collected via a standardized questionnaire sent to academic sites participating in the Familial Hypercholesterolemia Canada network.
Results:
A total of 48 patients with HoFH were enrolled. The median age at diagnosis was 12 years (interquartile range [IQR]: 5-24) and untreated LDL-C levels were 15.0 mmol/L (IQR: 10.5-18.6 mmol/L; 580 mg/dL IQR: 404-717 mg/dL). At last follow-up visit, median age was 40 years (IQR: 26-54 years). Treated LDL-C levels were 6.75 mmol/L (IQR: 4.73-9.51 mmol/L; 261 mg/dL IQR: 183-368 mg/dL) with 95.5% of patients on statins, 88.6% on ezetimibe, 34.1% on proprotein convertase subtilisin/kexin type 9 inhibitors, 27.3% on lomitapide, 13.6% on evinacumab, and 56.8% were treated with low-density lipoprotein apheresis or plasmapheresis. Deaths were reported in 7 (14.5%) and major adverse cardiovascular events were observed in 14.6% of patients with the average onset at 30 years (IQR: 20-36 years). Aortic stenosis was reported in one-half the patients (47.9%) and 10 (20.8%) underwent aortic valve replacement.
Conclusions:
This HoFH patient registry in Canada will provide important new health-related knowledge about the phenotypic manifestations and determinants of cardiovascular risk in this population, allowing for closer examination of quality of life and burden to the health care system.
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