Why, how and in whom should we measure levels of lipoprotein(a): A review of the latest evidence and clinical implications.

Abstract

Lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Despite robust evidence from epidemiological and genetic studies, Lp(a) remains underrecognised in clinical practice due to challenges in measurement, lack of guideline familiarity and limited therapeutic options. In this narrative review, we summarise the pathophysiological mechanisms linking Lp(a) to atherogenesis, thrombosis and inflammation, emphasising its unique structural features and causal role in cardiovascular disease. We discuss assay methodologies and make the case for a single lifetime measurement given the genetic stability of Lp(a). We review guideline-based indications for testing, highlighting high-risk populations such as those with premature ASCVD, a family history of cardiovascular disease and individuals of African or South Asian ancestry. We additionally outline clinical strategies to reduce ASCVD risk in individuals with elevated Lp(a), including lifestyle optimisation, statin therapy, PCSK9 inhibitors, and aspirin in select populations. Emerging targeted therapies, including antisense oligonucleotides and siRNA-based agents, demonstrate up to 90% Lp(a) reduction and are currently being evaluated in large-scale cardiovascular outcomes trials. As precision medicine advances, Lp(a) represents both a critical risk factor and a promising therapeutic target. Broader implementation of Lp(a) testing, particularly in high-risk individuals, will help improve ASCVD prevention efforts.