New Trends and Therapies for Familial Hypercholesterolemia

Area of Science:

• Cardiovascular Medicine
• Genetics
• Metabolic Disorders

Background:

• Familial hypercholesterolemia (FH) significantly elevates atherosclerosis risk, particularly when caused by monogenic defects.
• Cardiovascular risk in heterozygous FH is complex, influenced by LDL cholesterol, other biomarkers, and genetic factors.
• Homozygous FH presents extreme cardiovascular risk, necessitating early and intensive LDL-cholesterol-lowering therapies.

Purpose of the Study:

• To highlight the heterogeneous cardiovascular risk in heterozygous FH.
• To discuss the role of risk scores and imaging in identifying high-risk FH individuals.
• To review emerging therapies for homozygous FH and potential definitive solutions like gene therapy.

Main Methods:

• Analysis of existing literature on FH pathophysiology and risk stratification.
• Review of current and novel therapeutic strategies for managing hypercholesterolemia in FH.
• Discussion of advanced imaging techniques for assessing subclinical atherosclerosis.

Main Results:

• Monogenic FH defects confer higher atherosclerotic risk than other hypercholesterolemia types.
• Personalized risk assessment using scores and imaging aids in selecting FH patients for PCSK9 inhibitors.
• Despite advancements, residual atherosclerosis risk persists in homozygous FH, alongside concerns of aortic and valve disease.

Conclusions:

• Tailored risk assessment and advanced therapies are crucial for managing FH.
• Novel treatments like PCSK9 inhibitors, microsomal transfer protein, and angiopoietin-like protein 3 inhibitors are improving outcomes.
• Gene-based therapies hold promise for definitive LDL cholesterol reduction and mitigating atherosclerosis risk in FH.