Journal Article

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Current Understanding and Future Perspectives

Wu, M F, Guo, Y G, Xu, K Z, Yu J, Lin, L M, Wu Y

2019

Overview

PurposeTo review current knowledge of elevated lipoprotein(a) [Lp(a)] levels in relation to atherosclerotic cardiovascular disease (ASCVD) and discuss their potential use as biomarkers and therapeutic approaches in clinical practice.MethodsWe summarized the current understanding and recent advances in the structure, metabolism, atherogenic mechanisms, standardized laboratory measurement, recommended screening populations, and prognostic value of Lp(a), with a special focus on the current potential treatment approaches for hyperlipoprotein(a)emia in patients with ASCVD.ResultsLp(a) is composed of LDL-like particle and characteristic apolipoprotein(a) [apo(a)] connected by a disulfide bond. Substantial evidence shows that elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for ASCVD through its proatherogenic, proinflammatory, and potentially prothrombotic properties. Current guidelines recommend Lp(a) measurement for patients with an intermediate-high risk of ASCVD, familial hypercholesterolemia, a family history of early ASCVD or elevated Lp(a), and progressive ASCVD despite receiving optimal therapy. Traditional Lp(a)-lowering approaches such as niacin, PCSK9 inhibitors, mipomersen, lomitapide, and lipoprotein apheresis were associated with a non-specific and limited reduction of Lp(a), intolerable side effects, invasive procedure, and high expense. The phase 2 randomized controlled trial of antisense oligonucleotide against the apo(a) encoding gene LPA mRNA showed that IONIS-APO(a)-LRX could specifically reduce the level of Lp(a) by 90% with good tolerance, which may become a promising candidate for the prevention and treatment of ASCVD in the future.ConclusionsIt is reasonable to measure Lp(a) levels to reclassify ASCVD risk and manage individuals with elevated Lp(a) to further reduce the residual risk of ASCVD, especially with IONIS-APO(a)-LRX.

• Publisher: Springer Nature B.V
• Subject: Antisense oligonucleotides / Apheresis / Apolipoproteins / Arteriosclerosis / Atherosclerosis / Biomarkers / Cardiovascular disease / Cardiovascular diseases / Hypercholesterolemia / Inflammation / Lipoproteins / Low density lipoprotein / mRNA / Patients / Risk analysis / Risk factors / Risk management / Side effects / Therapeutic applications