Lipoprotein(a) hyperlipidemia as cardiovascular risk factor: pathophysiological aspects

Area of Science:

• Cardiovascular Science
• Genetics
• Biochemistry

Background:

• Lipoprotein (a) [Lp(a)] is a modified LDL particle with an apolipoprotein (apo[a]) component, linked by a thioester bond.
• Genetic variations in the LPA gene, specifically Kringle-IV type-2 repeats, determine Lp(a) isoforms.
• Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease (CVD).

Purpose of the Study:

• To critically revise diagnostic and therapeutic recommendations for familial Lp(a) hyperlipidemia [Lp(a)-HLP] and familial hypercholesterolemia [FH].
• To address the need for improved standardization and comparability of Lp(a) assays.
• To identify novel biomarkers for enhanced CVD risk assessment and patient stratification within the Lp(a) syndrome complex.

Main Methods:

• Review of current diagnostic and therapeutic guidelines for Lp(a)-HLP and FH.
• Analysis of Lp(a) assay limitations, including standardization and particle variation.
• Evaluation of Lp(a)-associated pathophysiology, including vascular remodeling, thrombosis, and inflammatory pathways.

Main Results:

• Phenotypic diversity in Lp(a)-HLP and FH, often co-occurring with other CVD risk factors, necessitates guideline revision.
• Current Lp(a) assays lack standardization, hindering accurate risk assessment.
• Lp(a) promotes vascular remodeling, lesion progression, and thrombosis via M1-macrophages, antiangiogenic effects (CXCL10), and immune cell activation.

Conclusions:

• Current diagnostic and therapeutic strategies for isolated familial Lp(a)-HLP or FH require revision to account for phenotypic diversity and co-existing risks.
• Improved Lp(a) assay standardization and novel biomarker discovery are crucial for accurate CVD risk stratification.
• Understanding Lp(a) pathophysiology is essential for managing the complex Lp(a) syndrome and improving patient outcomes, with lipoprotein apheresis as a treatment option for severe cases.