Long-term study reveals insights into homozygous familial hypercholesterolemia

In a comprehensive long-term study aimed at shedding light on homozygous familial hypercholesterolemia (HoFH), researchers have provided crucial insights into the clinical and genetic characteristics of the condition, as well as its management and outcomes in a real-world setting.

The study, conducted as part of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study), analyzed data collected from 39 HoFH patients over a period spanning from 2004 to 2022. The findings, published in a recent report, offer valuable information on lipid-lowering treatments and atherosclerotic cardiovascular disease (ASCVD) outcomes in this rare but severe condition.

Key findings from the study include:

• Clinical Characteristics: The average age of the patients studied was 42, with nearly half being women. At enrollment, a significant proportion of patients already had ASCVD (33%) and aortic valve disease (18%).
• Genetic Profile: The median age at genetic diagnosis was 24 years, highlighting the early onset of the condition. Patients with certain genetic variants, particularly null/null variants, tended to be younger and experienced higher untreated LDL-C levels, predisposing them to earlier ASCVD events.
• Lipid-Lowering Treatment: The majority of patients (92%) were on high-intensity statins and ezetimibe, with additional treatments including PCSK9 inhibitors (28%), lomitapide (26%), and lipoprotein-apheresis (23%). A notable proportion of patients (36%) achieved LDL-C levels below 100 mg/dL, indicating significant treatment efficacy.
• ASCVD Outcomes: Over the median follow-up period of 11 years, a small percentage of patients experienced new ASCVD events (15%), while the incidence of aortic valve disease remained low (3%). This suggests that advancements in lipid-lowering treatments have contributed to reducing ASCVD events in this population.
• Survival Analysis: Patients with defective variants showed longer free-event survival compared to those with at least one null variant, underscoring the impact of genetic variability on disease progression and outcomes.

The study underscores the severity of HoFH as a life-threatening condition characterized by high genetic and phenotypic variability. However, it also highlights the significant progress made in managing the condition, particularly in terms of lipid-lowering treatments and their impact on reducing ASCVD events.

Reference
Alonso R, Arroyo-Olivares R, Díaz-Díaz JL, et al. Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study. Atherosclerosis. 2024;117516. doi: 10.1016/j.atherosclerosis.2024.117516. Epub ahead of print. PMID: 38523000.