Nathan D. Wong, MD, PhD: Growing Role of Lp(a) in Cardiovascular Risk Assessment

In this expert discussion at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC), Nathan D. Wong, MD, PhD, a professor of medicine and director of the Heart Disease Prevention Program at the University of California, Irvine, discussed the growing excitement surrounding lipoprotein(a) [Lp(a)] and its role in cardiovascular disease prevention.

Lp(a), a low-density lipoprotein (LDL)-like particle with an apo(a) attached to apoB molecule, is now recognized as a potent genetic risk factor, with levels above 50 mg/dL (125 nmol/L) linked to cardiovascular complications, including myocardial infarction, stroke, aortic stenosis progression, and cardiovascular death. Wong emphasized that Lp(a) may be up to six times more atherogenic than LDL cholesterol (LDL-C), underscoring the urgent need for increased awareness and screening.

Despite its clinical significance, Wong noted fewer than 1% of individuals are currently tested for Lp(a). He highlighted recommendations from the National Lipid Association (NLA) advocating for universal, once-in-a-lifetime testing for all adults, indicating screening not only enhances risk stratification—potentially reclassifying patient risk scores—but also increases initiation of lipid-lowering therapies, including statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, in high-risk individuals.

At his institution at UC Irvine, Wong noted the implementation of best practice advisory alerts in electronic health records (EHRs) as one method to improve screening rates, particularly in patients with atherosclerotic cardiovascular disease (ASCVD), aortic stenosis, or elevated LDL-C.

Wong expressed excitement about the therapeutic pipeline for Lp(a), including the highly anticipated Lp(a)HORIZON trial of pelacarsen, the first cardiovascular outcomes trial targeting Lp(a), set to read out in 2025. Emerging therapies like siRNA agents and oral Lp(a)-lowering medications promise up to 80-100% reductions in Lp(a) levels. Wong stressed that while these advancements hold promise, clinicians must act now to reduce overall cardiovascular risk through intensive LDL-lowering, blood pressure control, and diabetes management in patients with elevated Lp(a).

Relevant disclosures for Wong include Amgen, Ionis, Novartis, Novo Nordisk, Regeneron, and others.

Reference

_{Wong ND. Lipoprotein(a): Ready for Prime Time. Presented at the 22nd Annual World Congress Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC). Los Angeles, California. December 12-14, 2024.}