%0 Journal Article
%T Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Current Understanding and Future Perspectives.
%A Wu MF
%A Xu KZ
%A Guo YG
%A Yu J
%A Wu Y
%A Lin LM
%J Cardiovasc Drugs Ther
%V 33
%N 6
%D 12 2019
%M 31655942
%F 3.947
%R 10.1007/s10557-019-06906-9
%X To 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.<BR>We 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.<BR>Lp(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.<BR>It 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.