Issue 5/2026
Shaban, A., Daskalov, I.
Clinic of Cardiology, MHAT – Sofia, Military Medical Academy
Lipoprotein(a) (Lp(a)) is recognized as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Despite its high prevalence (approximately 20% of the population), it often remains undiagnosed due to the historical lack of standardized therapeutic strategies. Objective: This review aims to synthesize current knowledge on Lp(a) biology, epidemiological evidence of its pathogenicity, and provide a critical analysis of emerging RNA-based therapeutic targets. Methods: A systematic literature review was conducted in PubMed, Scopus, and ClinicalTrials.gov for the period 2015-2025, focusing on meta-analyses, ESC/EAS consensus statements, and ongoing phase II and III clinical trials. Results: The analysis highlights the role of oxidized phospholipids (OxPL) carried by Lp(a) as a key driver of arterial inflammation. While statins and ezetimibe do not significantly alter Lp(a) levels, novel therapies such as pelacarsen (antisense oligonucleotide) and olpasiran (siRNA) demonstrate dose-dependent reductions in plasma concentrations exceeding 80-90%.
Conclusion: The transformation of Lp(a) from a marker of residual risk to a direct therapeutic target marks a new era in preventive cardiology. Anticipated results from the HORIZON trial will define the clinical benefit of aggressive Lp(a) lowering for the reduction of cardiovascular events.
Key words: Lipoprotein(a); apolipoprotein(a); atherosclerotic cardiovascular disease; aortic stenosis; oxidized phospholipids; RNA interference; cardiovascular risk.
Adress for correspondence:
Dr. Akif Ali Shaban, MD
Cardiology Clinic, Military Medical Academ
3 „St. G. Sofiyski“ Str.
1606, Sofia
e-mail: akiff@abv.bg