Homozygous Familial Hypercholesterolemia in Canada: An Observational Study.

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.

Informations de copyright

© 2023 The Authors.

Déclaration de conflit d'intérêts

Dr Genest has been supported by a Knowledge Synthesis Grant from the 10.13039/501100000024Canadian Institutes of Health Research (SBI-167982). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN PATIENT CARE: HoFH still carries a very high morbidity and mortality, and early initiation of novel therapies may be lifesaving. COMPETENCY IN MEDICAL KNOWLEDGE: HoFH is an orphan disease. Early identification and aggressive treatment have been shown to decrease early morbidity and mortality and to increase event-free survival. COMPETENCY IN PRACTICE-BASED LEARNING AND IMPROVEMENT: Physicians need to be aware of the genetic basis of HoFH and to refer patients to specialized clinics. COMPETENCY IN SYSTEMS-BASED PRACTICE: National registries have shown that they can unite caregivers to provide earlier diagnosis and care. TRANSLATIONAL OUTLOOK 1: Survival of patients with HoFH has double in the past 3 decades. Novel therapies including modulation of PCSK9 inhibition, lomitapide, ANGPTL3, and extracorporeal LDL filtration techniques can markedly improve survival. TRANSLATIONAL OUTLOOK 2: Reverse cascade screening can help identify patients with HeFH, initiate therapy and change outcomes.