Lipoprotein(a) and Cardiovascular Disease: From Genetic Risk Factor to Therapeutic Target

Lipoprotein(a) [Lp(a)] is a causal, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Although elevated Lp(a) affects approximately 20% of the global population, specific pharmacological options have long been unavailable, leaving a major gap in residual risk management. This review synthesizes current understanding of Lp(a) molecular architecture, genetics, and metabolism, and integrates mechanistic evidence linking Lp(a) to pro-atherogenic, pro-inflammatory, and pro-thrombotic pathways. We summarize epidemiological and genetic data associating Lp(a) with a broad spectrum of cardiovascular outcomes and discuss current clinical guidelines on screening and risk stratification. Furthermore, we provide an up-to-date overview of the emerging therapeutic landscape, including RNA-targeted therapies and novel oral small molecules. With pivotal phase 3 outcome trials nearing completion, the field is transitioning from viewing Lp(a) as an untreatable biomarker to an actionable therapeutic target, with important implications for precision cardiovascular prevention.