Homozygous Familial Hypercholesterolemia in Canada: An Observational Study

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.