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Lipoprotein(a) and Aortic Valve Stenosis: From Pathophysiology to Emerging Pharmacological Agents

Year: 2025

Type: article

Abstract: Aortic valve stenosis (AVS) is the most prevalent valvular heart disease in developed countries, with incidence expected to rise due to aging populations. While surgical aor-tic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) re-main the only definitive treatments for symptomatic disease, no pharmacological therapy has been proven to halt AVS progression. In recent years, lipoprotein(a) [Lp(a)] has emerged as a causal risk factor for cardiovascular disease, including coro-nary artery disease (CAD), aortic valve calcification, and AVS. Epidemiological studies and Mendelian randomization analyses have demonstrated a strong link between ele-vated Lp(a) concentrations and both the development and progression of calcific AVS. This review summarizes the biochemical structure and metabolism of Lp(a), its path-ogenetic role in aortic valve degeneration, and the clinical evidence supporting its as-sociation with AVS. We also discuss challenges in measuring Lp(a), current guideline recommendations, and the impact of commonly used lipid-lowering agents on Lp(a) levels. Finally, we highlight emerging Lp(a)-specific therapies, including antisense oli-gonucleotides and small interfering RNAs, which are currently being evaluated in large-scale clinical trials. While most ongoing studies focus on atherosclerotic out-comes, dedicated investigations into AVS progression are underway and may reshape future therapeutic strategies. By integrating mechanistic insights, clinical evidence, and novel pharmacological ap-proaches, this review underscores the potential of Lp(a)-targeted therapies to address an unmet clinical need in AVS management.

Source: Journal of Clinical Medicine

DOI: 10.3390/jcm15010274