Canadian Journal of Cardiology



      Homozygous familial hypercholesterolemia (HoFH) is life-threatening orphan disease characterized by high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients often present with extensive xanthomas and marked premature atherosclerotic cardiovascular disease (ASCVD) before the age of 20. Prior to the advent of statins and extracorporeal LDL filtration techniques, survival beyond 30 years of age was unusual. Treatment with lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy, reducing the risk of ASCVD to background population rates. Canada is known to have several founder effect regions for HoFH, including Québec. Clinical outcomes in HoFH patients, especially ASCVD events such as myocardial infarctions or stroke are difficult to capture, in part because of the rarity of the disorder and the lack of registry focusing on this disease.

      Methods and Results

      The objective of our project is to obtain a comprehensive registry of HoFH in Canada, estimate the cost to society caused by HoFH burden of disease in Canada, and implement changes to advocate access to specialized care for these patients. A standardized questionnaire was sent to the 19 academic sites across Canada participating in the FH Canada network. We previously identified 79 cases across the country, and have captured 46 of these cases. Here we describe their medical history, lipid levels, treatments and clinical outcomes. At the time of entry in the Registry, the mean age was 44 +/- 19 years, with a majority of females (54.4%), representing cases across 5 provinces. The average age of diagnosis was 16 4 years. with 67.4% having untreated LDL > 10 mmol/L. Presence of physical markers, such as xanthomas or corneal arcus, were also found in 80.4% and 26.1% of patients, respectively. For lipid-lowering therapy, 52.2% were undergoing LDL-apheresis, 91% were on statins and 41% on PCSK9 inhibitors. 54.3% displayed ASCVD, with 43.5% having aortic stenosis, 15.2% having experienced a myocardial infarction, and 36.9% having undergone one or more coronary artery bypass graft procedures.


      We plan to use this data at provincial and national levels, helped by the Canadian Organization for Rare Diseases (CORD) and the Réseau Québecois des maladies orphelines (RQMO), to provide HoFH patients access to care, including orphan drugs such as evinacumab, and treatment techniques such as LDL apheresis. This work will provide important new health-related knowledge about the determinants of ASCVD risk and phenotypic manifestations of HoFH in Canada, and examine the quality of life and burden to the healthcare system.