Lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein recognized as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases, such as aortic stenosis. Accumulating evidence from epidemiological and genetic studies has demonstrated a continuous relationship between the Lp(a) levels and cardiovascular risk in diverse populations. Structurally, Lp(a) consists of an low-density lipoprotein-like particle bound to apolipoprotein(a) [apo(a)], which exhibits marked size heterogeneity due to kringle IV type 2 repeat polymorphisms, accounting for substantial interindividual variability in the circulating Lp(a) levels. Measurement of Lp(a) is clinically valuable, but it remains challenging due to assay variability, isoform-dependent bias, and differences in reporting units. Lp(a) contributes to cardiovascular disease through multiple mechanisms, including the promotion of atherosclerosis, inflammation mediated by oxidized phospholipids, and impaired fibrinolysis due to structural homology with plasminogen. These findings indicate that elevated Lp(a) levels are associated with a broad spectrum of cardiovascular diseases and suggest that Lp(a) is not merely a biomarker, but also a potential therapeutic target. Recent advances in ribonucleic acid (RNA)-targeted therapies, including antisense oligonucleotides and small interfering RNA, have demonstrated substantial reductions in the Lp(a) levels. Ongoing large-scale outcome trials will determine whether lowering the Lp(a) levels translates into improved cardiovascular outcomes, potentially establishing Lp(a) as a key therapeutic target in cardiovascular prevention.