Lipoprotein(a): A Review of Risk Factors, Measurements, and Novel Treatment Modalities

Abstract

The study of lipoprotein(a) [Lp(a)] has long been a source of interest as a possible independent risk factor for atherosclerotic cardiovascular disease (ASCVD). The results of large sample observational studies, genome-wide association studies, and Mendelian randomization studies have been strong indicators supporting the link between ASCVD and Lp(a) despite early studies, with less sensitive assays, failing to show a connection. The recommendations for the indications and frequency of testing Lp(a) levels vary between US, Canadian, and European organizations due to the uncertain role of Lp(a) in ASCVD. The innovation of recent therapies, such as antisense oligonucleotides and small interfering RNA, designed to specifically target and reduce Lp(a) levels by targeting mRNA translation have once more thrust LP(a) into the spotlight of inquiry. These emerging modalities serve the dual purpose of definitively elucidating the connection between elevated Lp(a) levels and atherosclerotic cardiovascular risk, as well as the possibility of providing clinicians with the tools necessary to manage elevated Lp(a) levels in vulnerable populations. This review seeks to examine the mechanisms of atherogenicity of Lp(a) and explore the most current pharmacologic therapies currently in development.

Trial registration: ClinicalTrials.gov NCT04023552 NCT04270760 NCT05581303 NCT number) NCT04914546 NCT05565742 NCT04472676 NCT05563246.

Keywords: Lp(a); apo(a); apolipoprotein(a); dyslipidemia; lipoprotein(a).