Role of Lipoprotein (A) in aortic valve stenosis: Novel disease mechanisms and emerging pharmacotherapeutic approaches

• High Lp(a) levels are a genetic risk factor that can accelerate Aortic Stenosis (AS) progression by promoting aortic valve calcification. • Lp(a) carries oxidized phospholipids, fueling inflammation and calcification in the aortic valve, which stiffens the valve and restricts blood flow. • While AS treatment typically involves monitoring and valve replacement, emerging therapies to lower Lp(a) may help slow AS progression, though none are currently approved specifically for Lp(a) reduction. Lipoprotein(a) (Lp(a)) has garnered increasing attention as a significant contributor to the pathogenesis of aortic stenosis (AS), prompting a focused investigation into innovative pharmacological strategies to target this lipoprotein and its associated risks. Despite its recognized role in AS progression, Lp(a) often remains overlooked in clinical assessments, mirroring the broader challenges observed in holistic disease management. This review delves into the mechanistic intricacies of Lp(a) involvement in AS pathophysiology and its potential as a therapeutic target. Drawing parallels with the imperative for healthcare providers to proactively engage with patients regarding treatment regimens, this review underscores the essential role of cardiologists and physicians in recognizing and addressing Lp(a) as a modifiable risk factor in AS management. Furthermore, it explores promising avenues of novel drug approaches, including emerging pharmacotherapies and targeted interventions, aimed at modulating Lp(a) levels and attenuating AS progression. By navigating the complexities of Lp(a) modulation and its implications for AS management, this review aims to bridge critical gaps in understanding and clinical practice, ultimately optimizing treatment strategies and improving patient outcomes in the realm of AS therapeutics.