Lipoprotein(a) in clinical practice: New perspectives from basic and translational science

Area of Science:

• Cardiovascular Science
• Genetics
• Pharmacology

Background:

• Elevated lipoprotein(a) (Lp(a)) is a proven causal risk factor for coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS).
• Strong evidence links Lp(a) to atherothrombotic disease progression through genetic, epidemiological, and in vitro studies.
• Despite advancements, the precise metabolism, pathophysiology, and novel pathogenic roles of Lp(a) in cardiovascular disease (CVD) require further elucidation.

Purpose of the Study:

• To explore the complex role of Lp(a) in cardiovascular disease pathogenesis.
• To investigate the mechanisms and potential of novel Lp(a)-lowering therapies.
• To assess the clinical utility of reducing Lp(a) levels below established risk thresholds.

Main Methods:

• Review of genetic, epidemiological, and in vitro data on Lp(a).
• Examination of emerging therapeutic strategies targeting Lp(a).
• Focus on antisense oligonucleotide (ASO) therapy targeting apolipoprotein(a) (apo(a)).

Main Results:

• Antisense oligonucleotide therapy demonstrates potential to significantly reduce Lp(a) levels.
• Therapeutic Lp(a) reduction can achieve levels below the critical 30-50 mg/dL (75-150 nmol/L) risk threshold.
• The complete mechanisms underlying Lp(a) lowering by novel agents are still under investigation.

Conclusions:

• Lp(a) remains a critical, yet incompletely understood, contributor to cardiovascular disease.
• Targeted therapies, such as antisense oligonucleotides against apo(a), offer a promising approach to lower Lp(a).
• Further clinical assessment is needed to confirm the benefits of Lp(a) lowering therapies in reducing cardiovascular events.