The Emerging Lipid Risk: Lipoprotein(a).

Based on epidemiological and genetic studies in recent decades, lipoprotein(a) (Lp(a)) has been accepted as a causal risk factor for atherosclerotic cardiovascular disease and aortic stenosis. Although inter-ethnic differences exist, Lp(a) level ≥50 mg/dL is commonly reported to indicate elevated cardiovascular risk. Blood Lp(a) levels are largely determined based on genetic background, and the kringle IV type 2 repeat variant is a major factor. Lp(a) is structurally similar to low-density lipoprotein (LDL) but also contains apolipoprotein(a) (apo(a)), which includes kringle domains associated with diverse effects depending on particles and individuals. The LDL-like property of Lp(a) and effect of apo(a) on vascular cells can promote atherosclerosis. Apo(a) competes with plasminogen and can inhibit the role of plasmin during fibrinolysis. Furthermore, oxidized phospholipids on apo(a) may induce oxidative stress to enhance atherosclerosis and can affect valve calcification. Trials on new therapeutics targeting Lp(a) RNA, including antisense oligonucleotide (e.g., pelacarsen), siRNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and small molecules (e.g., muvalaplin), are under way. Depending on the study or dose, these agents lowered Lp(a) levels by 80-100% compared with the control; however, results of clinical outcomes have yet to be reported.

• Publication year

  2025

• Venue

  Korean Circulation Journal

• Publication date

  2025-10-20

• Fields of study

  Medicine

• Identifiers
  DOI 10.4070/kcj.2025.0380PMID 41371918
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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