The Lp(a) gap: Practical steps to align primary care and lipid clinics

Vanessa Bianconi

1,*

Pietro Tasegian

Matteo Pirro

*Correspondence to: Vanessa Bianconi, Department of Medicine and Surgery, University of Perugia, Perugia 06129, Italy. E-mail: vanessa.bianconi@ospedale.perugia.it

Adv Lipoprotein(a) Res. 2026;1:202613. 10.70401/alr.2026.0010

Received: August 03, 2026Accepted: October 09, 2026Published: October 10, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Lipoprotein(a) [Lp(a)] is a major, independent determinant of atherosclerotic cardiovascular disease and calcific aortic valve disease, yet its integration into routine clinical practice remains fragmented. Persistent uncertainties regarding when to measure Lp(a), how to interpret assay results, and how to manage elevated Lp(a) levels in the absence of approved Lp(a)-lowering therapies continue to hinder its adoption. Meanwhile, targeted therapies, including antisense oligonucleotides, siRNA agents, and small molecules, are advancing through phase 3 trials and may soon provide evidence regarding the clinical impact of pharmacological reduction of Lp(a). This evolving landscape demands a transition from passive awareness to active implementation. Early identification of individuals with elevated Lp(a), transparent communication of its clinical implications, and structured referral pathways between general practitioners and lipid clinics for the optimization of cardiovascular prevention and preparation for future therapeutic options, are crucial steps for bridging the existing Lp(a) gap. This perspective proposes a pragmatic framework for integrating Lp(a) into cardiovascular risk assessment and management across primary and specialist care, addressing operational challenges in measurement, interpretation, and treatment to support an actionable and coordinated Lp(a) clinical pathway. To this end, it formulates practical advice to orient Lp(a) management in primary care.

Keywords

Lp(a), cardiovascular, primary care, lipid clinic

References

1. Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946.

[DOI] [PubMed] [PMC]
2. Yang HS, Yoon S, Hur M. The lipoprotein(a) implementation gap: Bridging evidence and clinical practice. Rev Cardiovasc Med. 2026;27(2):47152.

[DOI] [PubMed] [PMC]
3. Razavi AC, Bhatia HS, Blumenthal RS, Shapiro MD, Mehta A. Why, how and in whom should we measure levels of lipoprotein(a): A review of the latest evidence and clinical implications. Diabetes Obes Metab. 2025;27 Suppl 8(Suppl 8):34-46.

[DOI] [PubMed] [PMC]
4. Kronenberg F. Lipoprotein(a) measurement issues: Are we making a mountain out of a molehill? Atherosclerosis. 2022;349:123-135.

[DOI] [PubMed]
5. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. Corrigendum to: 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(44):4255.

[DOI] [PubMed]
6. Mach F, Koskinas KC, Roeters van Lennep JE, Tokgözoğlu L, Badimon L, et al; ESC/EAS Scientific Document Group. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2025;46:4359-4378.

[DOI]
7. Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, et al. Lipoprotein(a): A genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: A scientific statement from the American heart association. Arterioscler Thromb Vasc Biol. 2022;42(1):e48-e60.

[DOI] [PubMed] [PMC]
8. Blumenthal RS, Morris PB, Gaudino M, Johnson HM, Anderson TS, Bittner VA, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: A report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2026;87(19):2624-2757.

[DOI] [PubMed]
9. Baragetti A, Da Dalt L, Norata GD. New insights into the therapeutic options to lower lipoprotein(a). Eur J Clin Invest. 2024;54(9):e14254.

[DOI] [PubMed]
10. MacDougall DE, Tybjærg-Hansen A, Knowles JW, Stern TP, Hartsuff BK, McGowan MP, et al. Lipoprotein(a) and recurrent atherosclerotic cardiovascular events: The US Family Heart Database. Eur Heart J. 2025;46(44):4762-4775.

[DOI] [PubMed] [PMC]
11. Dimitriadis K, Kyriakoulis KG, Pyrpyris N, Beneki E, Kamperidis V, Kollias A, et al. Lipoprotein(a) and aortic stenosis: Practical insights. Nutr Metab Cardiovasc Dis. 2025;35(10):104124.

[DOI] [PubMed]
12. Tsimikas S, Yeang C, Kronenberg F. In search of an accurate measurement of LDL-C: Correction for lp(a)-cholesterol to predict clinical outcomes. J Am Coll Cardiol. 2024;84(2):178-181.

[DOI] [PubMed]
13. Seidel M, Rosiewicz K, Seibert FS, Anft M, Stervbo U, Bertram S, et al. Intraindividual lp(a)-variability in a real-world setting. JACC Adv. 2026;5(3):102601.

[DOI] [PubMed] [PMC]
14. Corral P, Matta MG, Aguilar-Salinas C, Mehta R, Berg G, Ruscica M, et al. Lipoprotein(a) throughout life in women. Am J Prev Cardiol. 2024;20:100885.

[DOI] [PubMed] [PMC]
15. Pirro M, Bianconi V, Paciullo F, Mannarino MR, Bagaglia F, Sahebkar A. Lipoprotein(a) and inflammation: A dangerous duet leading to endothelial loss of integrity. Pharmacol Res. 2017;119:178-187.

[DOI] [PubMed]
16. Khovidhunkit W, Kim MS, Memon RA, Shigenaga JK, Moser AH, Feingold KR, et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: Mechanisms and consequences to the host. J Lipid Res. 2004;45(7):1169-1196.

[DOI] [PubMed]
17. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med. 1991;325(17):1196-1204.

[DOI] [PubMed]
18. Kronenberg F. Causes and consequences of lipoprotein(a) abnormalities in kidney disease. Clin Exp Nephrol. 2014;18(2):234-237.

[DOI] [PubMed]
19. Topciu Shufta V, Begolli L, Kryeziu E. Lipoprotein (a) as an acute phase reactant in patients on chronic hemodialysis. Bosn J Basic Med Sci. 2010;10(1):19-25.

[DOI] [PubMed] [PMC]
20. Li C, Li M, Wang Z. There is a linear negative correlation between lipoprotein(a) and non-alcoholic fatty liver disease. Sci Rep. 2025;15:8538.

[DOI] [PubMed] [PMC]
21. de Boer LM, Hof MH, Wiegman A, Stroobants AK, Kastelein JJP, Hutten BA. Lipoprotein(a) levels from childhood to adulthood: Data in nearly 3, 000 children who visited a pediatric lipid clinic. Atherosclerosis. 2022;349:227-232.

[DOI] [PubMed]
22. Morton JI, Kronenberg F, Daccord M, Bedlington N, Geanta M, Silberzahn T, et al. Lp(a) testing for the primary prevention of cardiovascular disease in high-income countries: A cost-effectiveness analysis. Atherosclerosis. 2025;409:120447.

[DOI] [PubMed]
23. Swearingen CA, Sloan JH, Rhodes GM, Siegel RW, Bivi N, Qian Y, et al. Measuring Lp(a) particles with a novel isoform-insensitive immunoassay illustrates efficacy of muvalaplin. J Lipid Res. 2025;66(1):100723.

[DOI] [PubMed] [PMC]
24. de Boer LM, Oorthuys AOJ, Wiegman A, Langendam MW, Kroon J, Spijker R, et al. Statin therapy and lipoprotein(a) levels: A systematic review and meta-analysis. Eur J Prev Cardiol. 2022;29(5):779-792.

[DOI] [PubMed]
25. Khera AV, Everett BM, Caulfield MP, Hantash FM, Wohlgemuth J, Ridker PM, et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in prevention: An intervention trial evaluating rosuvastatin). Circulation. 2014;129(6):635-642.

[DOI] [PubMed] [PMC]
26. Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, et al. Relationship between low-density lipoprotein cholesterol and lipoprotein(a) lowering in response to PCSK9 inhibition with evolocumab. J Am Heart Assoc. 2019;8(4):e010932.

[DOI] [PubMed] [PMC]
27. Tsimikas S. A test in context: Lipoprotein(a) diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692-711.

[DOI] [PubMed]
28. Lacaze P, Bakshi A, Riaz M, Polekhina G, Owen A, Bhatia HS, et al. Aspirin for primary prevention of cardiovascular events in relation to lipoprotein(a) genotypes. J Am Coll Cardiol. 2022;80(14):1287-1298.

[DOI] [PubMed] [PMC]
29. Bhatia HS, Trainor P, Carlisle S, Tsai MY, Criqui MH, DeFilippis A, et al. Aspirin and cardiovascular risk in individuals with elevated lipoprotein(a): The multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2024;13(3):e033562.

[DOI] [PubMed] [PMC]
30. Razavi AC, Richardson LC, Coronado F, Dzaye O, Bhatia HS, Mehta A, et al. Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a). Am J Prev Cardiol. 2024;18:100674.

[DOI] [PubMed] [PMC]
31. Bhatia HS, Bajaj A, Goonewardena SN, Moriarty PM. Pelacarsen: Mechanism of action and lp(a)-lowering effect. J Clin Lipidol. 2025;19(5):1208-1222.

[DOI] [PubMed]
32. Novartis. Novartis announces Lp(a)HORIZON Phase III topline results for pelacarsen in patients with elevated Lp(a) and established cardiovascular disease (CVD). Available from: https://www.novartis.com/
33. O’Donoghue ML, Rosenson RS, Gencer B, López JAG, Lepor NE, Baum SJ, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med. 2022;387(20):1855-1864.

[DOI] [PubMed]
34. Nissen SE, Ni W, Shen X, Wang Q, Navar AM, Nicholls SJ, et al. Lepodisiran: A long-duration small interfering RNA targeting lipoprotein(a). N Engl J Med. 2025;392(17):1673-1683.

[DOI] [PubMed]
35. Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, et al. Oral muvalaplin for lowering of lipoprotein(a): A randomized clinical trial. JAMA. 2025;333(3):222-231.

[DOI] [PubMed] [PMC]

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Bianconi V, Tasegian P, Pirro M. The Lp(a) gap: Practical steps to align primary care and lipid clinics. Adv Lipoprotein(a) Res. 2026;1:202613. https://doi.org/10.70401/alr.2026.0010