Lipoprotein(a) in familial hypercholesterolemia

Area of Science:

• Cardiovascular Medicine
• Lipid Metabolism
• Genetics

Background:

• Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein (LDL)-cholesterol.
• Elevated lipoprotein(a) [Lp(a)] is a significant, independent risk factor for cardiovascular disease (CVD).
• The lipid profile of high LDL-cholesterol and high Lp(a) is particularly detrimental for cardiovascular health.

Purpose of the Study:

• To review literature published before January 2026 on Lp(a) metabolism.
• To examine the association between Lp(a) and CVD risk in FH patients.
• To understand the role of Lp(a) in the context of FH lipid profiles.

Main Methods:

• Systematic literature review.
• Analysis of studies on Lp(a) metabolism and clearance.
• Evaluation of clinical evidence on CVD risk in FH with elevated Lp(a).

Main Results:

• Lp(a) is consistently elevated in FH cohorts, partly due to diagnostic criteria.
• The LDL receptor's role in Lp(a) hepatic uptake is less significant than previously thought.
• Pharmacological LDL-cholesterol reduction does not mitigate the specific CVD risk posed by elevated Lp(a) in FH.

Conclusions:

• Systematic Lp(a) measurement in FH patients is recommended.
• High-dose statins and PCSK9 inhibitors are crucial for achieving LDL-C goals in FH.
• Emerging Lp(a)-lowering therapies hold promise for treating FH patients with elevated Lp(a).