Familial Hypercholesterolemia Canada / Hypercholesterolemie Familiale Canada

Familial hypercholesterolemia (FH) is a genetic lipoprotein disorder characterized by elevations in low-density lipoprotein cholesterol (LDL-C) >95th percentile for age and gender. Affected individuals may show clinical manifestations (xanthomas, xanthelasmas and premature arcus corneus) although these manifestations are seen less frequently with early diagnosis and treatment. Untreated, FH will lead to atherosclerotic cardiovascular disease (CVD), primarily coronary artery disease (CAD). There are at least three accepted definitions for FH, based on absolute LDL-C levels (MedPed criteria), the Simon-Broome criteria include a fixed cut-point for LDL-C, the presence of DNA mutations and xanthomas and the FH Dutch Criteria (the Netherlands).

There are well-developed FH Registries in the Netherlands, United Kingdom, Spain, France, and the US, through the newly established US FH Foundation. In the United Kingdom, a report on the economic advantages of treating FH revealed that lipid-lowering statin therapy would lead to 101 fewer cardiovascular deaths/1000 patients with FH given treatment. The cost saving from cardiovascular events is estimated at over $CAN 592 million in the UK if all relatives of index cases were identified and treated, compared with no treatment given. This cascade testing strategy has been successfully applied in the Netherlands in families of FH probands with a detected mutation, thus allowing statin treatment of family members at risk of early coronary heart disease.

In Canada, the burden of disease is estimated to be approximately 120,000 patients, based on an allele frequency of LDL-R mutations of 1/311. In the province of Quebec, the allele frequency is approximately 1/270 and the number of affected subjects is approximately 29,000. Left untreated, FH men develop cardiovascular disease (CVD) in the third decade of life and women, in the fourth decade. When identified and treated early, life expectancy is normal.

The purpose of this initiative is to create a registry of subjects with FH across Canada designed to identify subjects with FH and to improve health and healthcare delivery. Rare diseases of lipoprotein metabolism (orphan diseases) are also included (SMASH registry; Systems and Molecular Approach of Severe Hyperlipidemia). This registry includes clinical, biochemical and demographic information. Specimens (plasma/serum and DNA) are collected for biobanking. The "local" portion of the registry is available for clinicians to manage patient care, and identify relatives for screening and treatment (cascade screening). The Canada-wide registry, which is completely anonymized, will be made available to provide advice to general practitioners and to support collaborative studies in biomedical, clinical, health outcomes and health economics research. Access to anonymized data from the registry will be given to researchers, clinicians, biopharmaceutical industry and government by peer-reviewed process.

The Mission of the Canadian FH Registry is to bring together a multi-disciplinary group of physicians, basic and clinical researchers to improve the delivery of care to patients with severe lipoprotein disorders, especially FH, and to foster collaborative research. Our Vision is to create a Canada-wide network of academic clinics, integrating lipid specialists, endocrinologists and cardiologists to treat patients with the highest standard of care and to create a collaborative research environment. Using a "hub and spoke" model, the registry extends in various communities to link primary care physicians with provincial academic centers. The Goals are to improve care to patients with FH and to reduce cardiovascular disease in this population at high risk.