Current Treatment of Familial Hypercholesterolaemia

Area of Science:

• Genetics and Cardiovascular Medicine

Background:

• Familial hypercholesterolaemia (FH) is an autosomal-dominant genetic disorder.
• It is characterized by mutations in the LDL receptor gene, leading to significantly elevated plasma low-density lipoprotein cholesterol (LDL-C).
• FH is underdiagnosed, affecting approximately 1 in 300 individuals with the heterozygous form and 1 in 1 million with the homozygous form.

Purpose of the Study:

• To emphasize the critical importance of early diagnosis and treatment of FH.
• To highlight the goal of reducing LDL-C levels by 50% to mitigate risks.
• To outline current and emerging therapeutic strategies for managing FH.

Main Methods:

• Review of current understanding of FH pathophysiology and prevalence.
• Discussion of therapeutic interventions including lifestyle modifications, pharmacologic agents, LDL apheresis, and liver transplantation.
• Exploration of combination therapy approaches.

Main Results:

• Early diagnosis and intervention significantly reduce the risk of premature atherosclerotic cardiovascular disease and mortality.
• Achieving a 50% reduction in LDL-C from baseline is the primary treatment objective.
• Pharmacologic treatments include statins, lomitapide, mipomersin, and PCSK9 inhibitors, often used in combination.

Conclusions:

• Effective management of FH requires a multi-faceted approach combining lifestyle changes and advanced pharmacologic therapies.
• Combination therapy is frequently necessary to achieve target LDL-C reductions and prevent severe cardiovascular complications.
• Prompt diagnosis and aggressive treatment are essential for improving long-term outcomes in patients with FH.