Lipoprotein(a) in clinical practice: Risk stratification and therapeutic strategies

Area of Science:

• Cardiology
• Genetics
• Pharmacology

Background:

• Lipoprotein(a) [Lp(a)] is a genetically determined, causal risk factor for atherosclerotic cardiovascular disease (ASCVD).
• Lp(a) levels are stable, best measured with specific assays, and recommended for one-time measurement in all adults.
• Guidelines suggest cascade testing for families with elevated Lp(a).

Purpose of the Study:

• To review the role of Lipoprotein(a) [Lp(a)] in cardiovascular disease.
• To discuss current guidelines and measurement methods for Lp(a).
• To explore emerging therapies for lowering Lp(a) and their potential impact on ASCVD outcomes.

Main Methods:

• Literature review of studies on Lp(a) and cardiovascular disease.
• Analysis of current clinical guidelines for Lp(a) testing and management.
• Summary of findings from phase 2 trials of novel Lp(a)-lowering agents.

Main Results:

• Elevated Lp(a) is linked to increased risk of coronary artery disease, myocardial infarction, and aortic stenosis.
• High Lp(a) is associated with ischemic stroke and poor outcomes in cerebrovascular disease.
• Intensified risk factor modification is recommended for elevated Lp(a) levels (≥50 mg/dL or ≥125 nmol/L).

Conclusions:

• No current lipid-lowering therapies significantly reduce Lp(a) levels.
• Novel agents like ASOs, siRNAs, and small molecules show promise in phase 2 trials.
• Phase 3 trials are evaluating the causal role of Lp(a) in ASCVD and the efficacy of lowering Lp(a) to reduce cardiovascular events.