RNA therapeutics
The Lp(a) hypothesis awaits its first clinical trial test, unlike the LDL hypothesis, a review of Lp(a) and cardiovascular disease (Front Biosci (Landmark Ed) 2018)
Original title: Lipoprotein(a) and cardiovascular disease: current state and future directions for an enigmatic lipoprotein
This review by Saeed and Virani surveys the current state and future directions for Lp(a), a complex polymorphic lipoprotein structurally similar to LDL but carrying the unique glycoprotein apolipoprotein(a). Genetic, epidemiological and translational data indicate elevated Lp(a) is likely in the causal pathway for atherosclerotic cardiovascular disease and aortic valve calcification, yet unlike the LDL hypothesis, the Lp(a) hypothesis has not yet been tested in clinical trials. Current management of elevated Lp(a) focuses on lowering LDL cholesterol, while developing antisense oligonucleotide therapies that inhibit apo(a) synthesis represent an emerging alternative. The review covers Lp(a) role in coronary heart disease, stroke, aortic valve stenosis and other vascular diseases, and current and emerging Lp(a)-lowering therapies.
Original 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.
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Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.