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

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.