Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand?

ABSTRACT

Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70-90% genetically determined through the codominant expression of the LPA gene. Therefore, Lp(a) levels are almost stable during an individual's lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.