RNA therapeutics
Review traces Lp(a) research from Kare Berg's 1963 discovery to five emerging Lp(a)-lowering agents now in trials (Curr Probl Cardiol 2024)
Original title: Elevated lipoprotein(a) levels: A crucial determinant of cardiovascular disease risk and target for emerging therapies
This review summarises six decades of Lp(a) research, from Kare Berg's original 1963 discovery through the establishment of Lp(a), affecting approximately 20% of the global population, as an independent genetic contributor to cardiovascular disease and aortic stenosis. It covers Lp(a)'s molecular structure, metabolism, genetics, and involvement in atherosclerosis, inflammation and thrombosis, alongside epidemiological evidence linking high Lp(a) to increased cardiovascular morbidity and mortality despite its physiological function remaining unknown. The review highlights five emerging therapies, pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, as showing promise for significantly lowering Lp(a), while cautioning that further research is needed to establish their long-term efficacy and safety before they can transform cardiovascular disease prevention and treatment.
Original abstract
Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20 of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.