Lipoprotein(a) and cardiovascular disease: current state and future directions for an enigmatic lipoprotein

Abstract

Lipoprotein (a) (Lp (a)) is a complex polymorphic lipoprotein. Although structurally similar to low-density lipoprotein, Lp(a) has a glycoprotein, apolipoprotein(a) (apo(a)), attached to the apolipoprotein B-100 component. Several unique properties of Lp(a) can be attributed to the presence of apo(a). Several decades of research has improved our understanding of the structure, biochemistry, and pathophysiology of Lp(a) associated diseases. Genetic, epidemiological, and translational data indicate that elevated Lp(a) levels are likely in the causal pathway for atherosclerotic cardiovascular diseases as well as calcification of the aortic valves. The "Lp(a) hypothesis," unlike the "LDL hypothesis," has not been tested in clinical trials yet. Currently, the management of elevated Lp(a) is directed at lowering low-density lipoprotein cholesterol levels. Developing therapies include antisense oligonucleotides which inhibit the synthesis of apo(a). This review discusses the current state of literature on pathophysiological and clinical aspects of Lp(a), including its role in coronary heart disease, stroke, aortic valve stenosis, and other vascular diseases. Current and emerging therapies aimed at treatment for elevated Lp(a) levels are also discussed.