Lipoprotein (a) in familial hypercholesterolaemia.

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Genetics

Background:

• The role of lipoprotein (a) [Lp(a)] in atherogenesis and its association with familial hypercholesterolemia (FH) has been debated.
• A clear mechanism linking Lp(a) to low-density lipoprotein (LDL) receptor-mediated catabolism has been lacking.
• The independent contribution of Lp(a) to the elevated atherosclerotic cardiovascular disease (ASCVD) risk in FH is uncertain.

Purpose of the Study:

• To review existing evidence on the relationship between Lp(a) and FH.
• To clarify the extent to which Lp(a) contributes to ASCVD risk in FH patients.
• To discuss the potential therapeutic implications of targeting Lp(a) in FH.

Main Methods:

• Review of current scientific literature and evidence.
• Analysis of mechanisms involved in Lp(a) regulation in FH.
• Discussion of clinical implications and future research directions.

Main Results:

• Inheriting FH increases the likelihood of elevated Lp(a) levels, potentially via increased hepatic production influenced by PCSK9 and apolipoprotein E.
• The precise contribution of elevated Lp(a) to ASCVD risk in FH remains controversial.
• Emerging therapies targeting Lp(a) may be most effective in individuals with the highest Lp(a) levels, such as those with FH.

Conclusions:

• FH is strongly associated with increased Lp(a) levels.
• Further research, particularly using Lp(a)-lowering drugs, is needed to definitively test the contribution of Lp(a) to ASCVD risk in the context of high LDL cholesterol in FH.
• Individuals with FH may represent a key population for evaluating novel Lp(a)-targeted therapies.