Lipoprotein(a): structural basis, bidirectional risk, and therapeutic fontiers

Abstract

Despite substantial progress in the management of cardiovascular disease (CVD), lipoprotein(a) [Lp(a)] persists as a genetically determined risk factor that remains insufficiently explored. Both extremely high and low levels of Lp(a) are linked to adverse outcomes. Current diagnostic assays for Lp(a) lack standardization, and conventional lipid-lowering therapies exert minimal effects on its levels, resulting in limited treatment options specifically targeting Lp(a). To address these gaps, we conducted a comprehensive molecular and clinical review of Lp(a), examining its unique structure, genetic determinants, metabolic pathways, and the factors influencing its plasma concentration. Furthermore, we discuss emerging therapeutic strategies aimed at targeting Lp(a).