Lipoprotein(a) in Coronary Artery Disease and Aortic Stenosis: Pathophysiology, Clinical Impact, Interventional Implications and Emerging Targeted Therapies

Abstract

Lipoprotein(a) (Lp(a)) is increasingly recognized as a genetically determined and clinically relevant contributor to residual cardiovascular risk. Through pro-atherogenic, pro-inflammatory, pro-thrombotic, and pro-calcific mechanisms, Lp(a) appears to play a significant role in both coronary artery disease and aortic valve disease. In patients undergoing percutaneous coronary intervention, elevated Lp(a) has been associated with worse long-term outcomes, including recurrent ischemic events, repeat revascularization, and in-stent restenosis, even in the setting of controlled low-density lipoprotein cholesterol. In parallel, experimental, genetic, and clinical data support a role for Lp(a) in the initiation and progression of calcific aortic stenosis, while its prognostic significance after transcatheter aortic valve interventions remains less clearly defined. Current guidelines now recognize Lp(a) as a relevant risk-enhancing factor, and emerging targeted therapies are achieving substantial reductions in circulating levels. Overall, Lp(a) should be regarded as both a meaningful biomarker and a promising therapeutic target, although ongoing outcome trials are needed to determine whether selective Lp(a) lowering translates into clinical benefit across interventional cardiovascular settings. The aim of this narrative review is to provide a single, comprehensive account of lipoprotein(a) [Lp(a)] in interventional cardiology, following this lipoprotein from its biology and pathophysiology through to its clinical impact and to the therapies that are now reaching the clinic, with a specific focus on the two most frequent catheter-based procedures in which it may carry prognostic weight: percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI). PCI and TAVI are deliberately addressed within the same review since they share a common upstream biology: Lp(a) contributes both to the atherosclerotic process that underlies coronary disease and to the calcific process that underlies aortic valve disease, and the corresponding patient populations overlap considerably in everyday interventional practice. Covering them together offers the interventional cardiologist a single, practical reference on how a patient with elevated Lp(a) may be approached in both scenarios.