Key Takeaways
- Lp(a) is a genetic, lifelong CV risk factor. Lp(a) levels are inherited and stable across life, affecting ~20% of the population; a single lifetime test can meaningfully refine long-term cardiovascular risk. [1,2]
- Elevated Lp(a) independently increases ASCVD and valvular risk. High Lp(a) is linked to MI, CAD, stroke, PAD, and calcific aortic stenosis, with risk rising linearly and amplifying other CV risk factors. [2]
- Once-in-a-lifetime Lp(a) screening is now guideline-supported. International guidelines and the 2025 Brussels Declaration recommend at least one Lp(a) test for adults, shifting from selective to population-level screening. [3]
- Correct units are critical for interpretation. Due to wide variability in apo(a) size, mg/dL and nmol/L are not interchangeable; nmol/L better reflects particle number and CV risk.[3,4]
- Structured pathways ( LILAC) implemented at CGH in Singapore make Lp(a) actionable in practice. The LILAC supports LDL-first management, overall risk reduction, assessment of related conditions, and cascade family testing.[5]
This section presents a concise, high-yield summary of the video’s core content, designed as a quick reference for Healthcare Professionals (HCPs).
Note: This content was developed by our editorial team and was not reviewed or endorsed by the video speaker.
Q1. Why is LDL-lowering still central when Lp(a) is elevated?
Although Lp(a) is highly atherogenic per particle, LDL particles are far more numerous. Reducing LDL remains the most effective way to lower total atherogenic burden and near-term CV risk. [4]
Q2. What Lp(a) thresholds are clinically meaningful?
While thresholds vary globally, ≥50 mg/dL (≈105–125 nmol/L) is widely accepted as a marker of CV risk. Very high levels (>200–400 nmol/L) are linked to premature ASCVD, young-onset MI, stroke, and increased mortality, even when LDL-C is not markedly elevated. The clinical message is to act on elevated Lp(a) by intensifying overall risk reduction, rather than focusing on a single cut-off. [6,7]
Q3. Why is Lp(a) under-tested despite strong evidence?
Key barriers include limited clinician familiarity with Lp(a), confusion around units (mg/dL vs nmol/L), inconsistent thresholds across guidelines, and the perception that “nothing can be done” due to limited targeted therapies. [8]
Survey data from Singapore showed that only 44% of cardiologists and endocrinologists had ever ordered an Lp(a) test, reflecting a global pattern of under-testing. [9]
Importantly, the experience at Changi General Hospital demonstrated that education, awareness, and a simple one-page clinical workflow can dramatically improve testing rates.[5]
Q4. What therapies can lower Lp(a)?
Currently available therapies lower Lp(a) indirectly. PCSK9 inhibitors reduce Lp(a) by approximately 20–25% while also achieving substantial LDL-C reduction, making them useful when both are elevated. Niacin lowers Lp(a) but lacks cardiovascular outcome benefit, and lipoprotein apheresis is effective but limited in availability. RNA-based therapies (e.g., Pelacarsen, Olpasiran, Lepodisiran), which target apo(a) production and have shown up to ~95% Lp(a) reduction in phase 2 studies, with phase 3 outcome trials ongoing. [10]
Q5. How was screening operationalised in Singapore?
At Changi General Hospital, Lp(a) testing was integrated into the acute myocardial infarction (AMI) care pathway, ensuring systematic rather than opportunistic testing. This was supported by a simple one-page clinical workflow (LILAC) outlining when to test, how to interpret results, and what actions to take. [5] As a result, Lp(a) testing rates among AMI patients improved. This experience demonstrated that structured pathways and clinician support can translate guideline recommendations into scalable routine practice. [5]
References
- Tsimikas S, Marcovina SM. Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week. J Am Coll Cardiol. 2022;80(9):934-946. doi:10.1016/j.jacc.2022.06.019
- Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis. J Am Coll Cardiol. 2018;71(2):177-192. doi:10.1016/j.jacc.2017.11.014
- Kronenberg F, Bedlington N, Ademi Z, et al. The Brussels International Declaration on Lipoprotein(a) Testing and Management. Atherosclerosis. 2025;406:119218. doi:10.1016/j.atherosclerosis.2025.119218
- Björnson E, Adiels M, Taskinen MR, et al. Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis. J Am Coll Cardiol. 2024;83(3):385-395. doi:10.1016/j.jacc.2023.10.039
- Loh WJ, Chan DC, Mata P, Watts GF. Familial Hypercholesterolemia and Elevated Lipoprotein(a): Cascade Testing and Other Implications for Contextual Models of Care. Front Genet. 2022;13:905941. Published 2022 Apr 27. doi:10.3389/fgene.2022.905941
- Kamstrup PR, Neely RDG, Nissen S, et al. Lipoprotein(a) and cardiovascular disease: sifting the evidence to guide future research. Eur J Prev Cardiol. 2024;31(7):903-914. doi:10.1093/eurjpc/zwae032
- Loh WJ, Watts GF. Detection strategies for elevated lipoprotein(a): will implementation let the genie out of the bottle?. Curr Opin Endocrinol Diabetes Obes. 2023;30(2):94-102. doi:10.1097/MED.0000000000000789
- Сlark-Mckellar J, et al. Lipoprotein(a) in cardiovascular medicine: From recognition to clinical action, Frontiers in Cardiovascular Medicine. Available at: https://www.frontiersin.org/research-topics/74861/lipoproteina-in-cardiovascular-medicine-from-recognition-to-clinical-action (Accessed: 30 April 2026).
- Loh WJ, Pang J, Simon O, Chan DC, Watts GF. Deficient perceptions and practices concerning elevated lipoprotein(a) among specialists in Singapore. Front Cardiovasc Med. 2025;12:1527351. Published 2025 Feb 14. doi:10.3389/fcvm.2025.1527351
- Nestel P, Loh WJ, Ward NC, Watts GF. New Horizons: Revival of Lipoprotein (a) as a Risk Factor for Cardiovascular Disease. J Clin Endocrinol Metab. 2022;107(11):e4281-e4294. doi:10.1210/clinem/dgac541