Aortic stenosis
A clinical practice review of Lp(a) risk stratification and the emerging lowering agents (Eur J Clin Invest 2026)
Original title: Lipoprotein(a) in clinical practice: Risk stratification and therapeutic strategies
This review by Nasrallah and colleagues consolidates current guidance on lipoprotein(a) in practice: EAS and NLA guidelines both now recommend a one-time Lp(a) measurement in all adults, using isoform-insensitive, molar-based assays, with cascade testing in affected families. It summarises the associations of elevated Lp(a), defined as 50 mg/dL or 125 nmol/L or higher, with coronary artery disease, myocardial infarction, aortic stenosis, and large artery ischaemic stroke, and notes that its link to venous thromboembolism is limited to prothrombotic states and extreme concentrations. No approved therapy substantially lowers Lp(a) today, but antisense oligonucleotide, siRNA and small-molecule agents have shown promising phase 2 results, with phase 3 outcomes trials now testing whether lowering Lp(a) itself reduces cardiovascular events. A concise, practice-oriented synthesis rather than new data.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is a primarily genetically determined, causal and independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) levels are stable, unaffected by lifestyle, and best measured using isoform-insensitive, molar-based assays. Current guidelines from the European Atherosclerosis Society and U.S. National Lipid Association recommend a one-time Lp(a) measurement in all adults. Cascade testing is advised in affected families.
Results: Elevated Lp(a) levels are associated with increased risk of coronary artery disease, myocardial infarction incidence and recurrence, and aortic stenosis onset and progression. In cerebrovascular disease, high Lp(a) is linked to large artery ischemic stroke incidence and recurrence, as well as poor functional outcomes. Associations with venous thromboembolism are limited to prothrombotic states and extreme Lp(a) concentrations. Elevated levels (≥50 mg/dL or ≥125 nmol/L) should prompt intensified risk factor modification.
Conclusion: There are no currently approved lipid-lowering therapies that substantially reduce Lp(a) levels. Novel agents to lower Lp(a) include antisense oligonucleotides, small interfering ribonucleic acid and small molecules, all of which have shown promising results in phase 2 trials. Ongoing phase 3 trials will evaluate the causal relationship between Lp(a) and ASCVD, and whether lowering Lp(a) reduces cardiovascular outcomes.
aortic stenosisguidelinesstroketestingtherapy
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.