Key Findings:

• This study provides a comprehensive overview of the clinical and genetic characteristics of patients with homozygous familial hypercholesterolemia (HoFH) in Japan, based on data from the National Database of the Japanese Ministry of Health, Labour, and Welfare.
• It included 201 patients with a median diagnosis age of 27 years, with a notable bimodal age distribution.
• Approximately 70% of the patients suffered from coronary artery disease.
• Genetic analysis revealed that most patients had mutations in the LDLR gene, with some having mutations in PCSK9 or being double heterozygotes of LDLR.
• 74% of patients were treated with high-intensity statins, 21% underwent lipoprotein apheresis, and 50% received PCSK9 inhibitors.
• The treatment resulted in a reduction of mean LDL cholesterol levels from 10.1 mmol/L to 3.9 mmol/L.
• Patients with coronary artery disease experienced a significant decrease in LDL cholesterol levels.
• A significant proportion of patients (24%) had valvular diseases, especially aortic valvular disease (61% of those with valvular issues).

Importance:

This study highlights the diversity in severity of phenotypes among Japanese patients with HoFH and indicates that, despite the availability of intensive lipid-lowering therapies, the management of LDL cholesterol in these patients is still inadequate. The findings emphasize the need for improved treatment strategies and could inform future guidelines for managing HoFH.

Contribution to Literature:

The research adds valuable data on the epidemiology and treatment outcomes for HoFH in Japan, a population where such information was previously limited. It underscores the genetic variability and the impact of aggressive lipid-lowering therapies on LDL cholesterol levels in this high-risk patient group.