Homozygous Familial Hypercholesterolemia in Canada

Quick Takes

  • An estimated 30-100 cases of homozygous familial hypercholesterolemia (HoFH) are expected in Canada, which given the numbers of patients in this registry, suggests HoFH remains underdiagnosed. Providers should be aware of genetic testing for HoFH and the need to refer such patients to specialized clinics.
  • HoFH is associated with significantly higher LDL-C levels and evidence of severe CVD much earlier in life than observed in non-FH populations, even among those who are diagnosed early and on lipid-lowering therapies.
  • Survival has improved among treated patients with HoFH over the past three decades.

Study Questions:

What are the clinical characteristics and cardiovascular (CV) outcomes among patients with homozygous familial hypercholesterolemia (HoFH)?


The HoFH registry used an observational study design and was conducted within the framework of the national FH Canada registry, which includes 19 academic centers and over 200 clinicians and health care providers across Canada. Clinical and genetic data on HoFH patients were collected via a standardized questionnaire sent to academic sites participating in the FH Canada network. Patients were eligible for inclusion in the Canadian HoFH registry if they had received a clinical or genetic diagnosis of HoFH from the treating physician. The data collection was started in 2008, and medical charts were retrospectively examined. For the current analysis, only patients who were alive and being followed up in 2008 or after were included in the study in order to accumulate temporal data on patients.


A total of 48 patients with HoFH were enrolled, of which 21 were male (43.8%), and 27 were female (56.2%). The median age of diagnosis was 12 years (interquartile range [IQR], 5.0–24.0), and 81.3% showed signs of physical stigmata such as xanthomas at the time of diagnosis. The median age at diagnosis was 12 years (IQR, 5–24), and untreated low-density lipoprotein cholesterol (LDL-C) levels were 15.0 mmol/L (IQR, 10.5–18.6) or 580 mg/dL (IQR, 404–717). At the last follow-up visit, the median age was 40 years. Treated LDL-C levels were 6.75 mmol/L (IQR, 4.73–9.51) or 261 mg/dL (IQR, 183–368), with 95.5% of patients on statins, 88.6% on ezetimibe, 34.1% on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, 27.3% on lomitapide, 13.6% on evinacumab, and 56.8% were treated with LDL apheresis or plasmapheresis. Deaths were reported in seven (14.5%), and major adverse CV events were observed in 14.6% of patients with the average onset at 30 years (IQR, 20–36). Aortic stenosis was reported in 47.9% of patients, and 10 (20.8%) underwent aortic valve replacement.


The authors conclude that this HoFH patient registry in Canada would provide important new health-related knowledge about the phenotypic manifestations and determinants of CV risk in this population, allowing for a closer examination of the quality of life and burden to the health care system.


HoFH is rare; therefore, leveraging large registries such as the FH Canada registry to collect data across large numbers of providers and sites can assist in our understanding of clinical characteristics and outcomes for HoFH. These data suggest that HoFH remains underdiagnosed. Given that newer lipid-lowering therapies exist, there is an opportunity to manage LDL-C levels starting at an early age.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Valvular Heart Disease, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins

Keywords: Aortic Valve Stenosis, Blood Component Removal, Cholesterol, LDL, Dyslipidemias, Ezetimibe, Genetic Testing, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Hyperlipoproteinemia Type III, Lipids, Lipoproteins, PCSK9 protein, human, Plasmapheresis, Primary Prevention, Proprotein Convertase 9, Quality of Life, Xanthomatosis

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