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Lipoprotein(a) and ischemic stroke

Czech version

Authors: Darren Andrew Noronha;  Martin Šatný;  Michal Vrablík
Authors‘ workplace: Centrum preventivní kardiologie, III. interní klinika – endokrinologie a metabolismu 1. LF UK a VFN v Praze
Published in: AtheroRev 2026; 11(2): 113-118
Category: Reviews

Overview

Elevated lipoprotein(a) –⁠ Lp(a) concentration is a predominantly genetically determined (> 90 %) risk factor for atherosclerotic cardiovascular disease (ASCVD). Epidemiological, clinical and genetic studies support an independent and likely causal association with ischemic stroke, particularly stroke due to large-artery atherosclerosis. Evidence for cardioembolic stroke and small-vessel disease is weaker. Measurement of Lp(a) can refine residual cardiovascular risk assessment, particularly in patients with premature or recurrent ischemic stroke, stroke due to large-artery atherosclerosis, or a family history of premature ASCVD. Current management relies on intensive LDL-cholesterol lowering and control of other ASCVD risk factors. Antisense oligonucleotides, siRNA agents and oral small-molecule inhibitors markedly lower Lp(a), but whether they reduce recurrent stroke has not yet been demonstrated. The aim of this review is to summarize the current knowledge regarding the relationship between Lp(a) and ischemic stroke, its biological mechanisms, clinical significance and treatment options.

Keywords:

prevention – ischemic stroke – lipoprotein(a) – large-artery atherosclerosis – residual cardiovascular risk

Sources
  1. [GBD 2021 Stroke Risk Factor Collaborators]. Global, regional, and national burden of stroke and its risk factors, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol 2024; 23(10): 973–1003. Dostupné z DOI: <http://dx.doi.org/10.1016/S1474–4422(24)00369–7>.
  2. Adams HP jr, Bendixen BH, Kappelle LJ et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24(1): 35–41. Dostupné z DOI: <http://dx.doi.org/10.1161/01.STR.24.1.35>.
  3. Kronenberg F, Mora S, Stroes ES 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. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehac361>.
  4. Clarke R, Peden JF, Hopewell JC et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009; 361(26): 2518–2528. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0902604>.
  5. Langsted A, Nordestgaard BG, Kamstrup PR. Elevated lipoprotein(a) and risk of ischemic stroke. J Am Coll Cardiol 2019; 74(1): 54–66. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2019.03.524>. Erratum in Correction. J Am Coll Cardiol 2020; 75(18): 2385. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2020.03.063>.
  6. Pan Y, Li H, Wang Y et al. Causal effect of Lp(a) level on ischemic stroke and Alzheimer disease: a Mendelian randomization study. Stroke 2019; 50(12): 3532–3539. Dostupné z DOI: <http://dx.doi.org/10.1161/STROKEAHA.119.026872>. Erratum in Stroke 2019; 50(12): e439. Dostupné z DOI: <http://dx.doi.org/10.1161/STR.0000000000000214>.
  7. Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N Engl J Med 2020; 382(3): 244–255. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1905239>.
  8. O’Donoghue ML, Rosenson RS, Gencer B et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med 2022; 387(20): 1855–1864. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2211023>.
  9. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol 2017; 69(6): 692–711. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2016.11.042>.
  10. Koschinsky ML, Bajaj A, Boffa MB et al. A focused update to the 2019 National Lipid Association scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol 2024; 18(3): e308-e319. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2024.03.001>.
  11. Boffa MB, Koschinsky ML. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease. Nat Rev Cardiol 2019; 16(5): 305–318. Dostupné z DOI: <http://dx.doi.org/10.1038/s41569–018–0153–2>.
  12. Ohira T, Schreiner PJ, Morrisett JD et al. Lipoprotein(a) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Stroke 2006; 37(6): 1407–1412. Dostupné z DOI: <http://dx.doi.org/10.1161/01.STR.0000222666.21482.b6>.
  13. Aronis KN, Zhao D, Hoogeveen RC et al. Associations of lipoprotein(a) levels with incident atrial fibrillation and ischemic stroke: the ARIC study. J Am Heart Assoc 2017; 6(12): e007372. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.117.007372>.
  14. Arora P, Kalra R, Callas PW et al. Lipoprotein(a) and risk of ischemic stroke in the REGARDS study. Arterioscler Thromb Vasc Biol 2019; 39(4): 810–818. Dostupné z DOI: <http://dx.doi.org/10.1161/ATVBAHA.118.311857>.
  15. Kamstrup PR, Tybjærg-Hansen A, Steffensen R et al. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301(22): 2331–2339. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2009.801>.
  16. Kao AS, Kermanshahchi J, Khosrowjerdi S et al. Demographics of lipoprotein(a) and stroke: the UK Biobank. Am J Prev Cardiol 2025; 23 : 101055. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ajpc.2025.101055>.
  17. Arnold M, Schweizer J, Nakas CT et al. Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study. Eur Heart J 2021; 42(22): 2186–2196. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehab081>.
  18. Rudin S, Kriemler L, Dittrich TD et al. Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a Swiss stroke center. Swiss Med Wkly 2024; 154 : 3633. Dostupné z DOI: <http://dx.doi.org/10.57187/s.3633>.
  19. Lackova A, Gdovinova Z, Kozarova M et al. Lipoprotein(a) concentration as a risk factor for ischaemic stroke and its subtypes. Neurol Neurochir Pol 2024; 58(3): 316–322. Dostupné z DOI: <http://dx.doi.org/10.5603/pjnns.98343>.
  20. Paolucci M, Urbinati G, Gentile M et al. High lipoprotein(a) and stroke: association with large artery and intracranial atherosclerosis –⁠ a retrospective study. J Clin Lipidol 2026; 20(3): 600–608. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2026.01.015>.
  21. Gross F, Schütz V, Westphal LP et al. Lipoprotein(a) and large artery atherosclerosis: results from the BIOSIGNAL study. Lipids Health Dis 2026; 25(1): 108. Dostupné z DOI: <http://dx.doi.org/10.1186/s12944–026–02913–6>.
  22. Kumar P, Swarnkar P, Misra S et al. Lipoprotein(a) level as a risk factor for stroke and its subtype: a systematic review and meta-analysis. Sci Rep 2021; 11(1): 15660. Dostupné z DOI: <http://dx.doi.org/10.1038/s41598–021–95141–0>.
  23. Palaiodimou L, Melanis K, Stefanou MI et al. The association of lipoprotein(a) and stroke recurrence: a systematic review and meta-analysis. J Stroke 2025; 27(2): 161–168. Dostupné z DOI: <http://dx.doi.org/10.5853/jos.2024.04623>.
  24. Huang Y, Zhang R, Han L et al. Lipoprotein(a) and stroke: a two-sample Mendelian randomization study. Front Aging Neurosci 2023; 15 : 1178079. Dostupné z DOI: <http://dx.doi.org/10.3389/fnagi.2023.1178079>.
  25. Mach F, Baigent C, Catapano AL et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2020; 41(1): 111–188. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz455>. Erratum in: Eur Heart J 2020; 41(44): 4255. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz826>.
  26. Grundy SM, Stone NJ, Bailey AL et al. 2018 AHA/ACC multisociety guideline on the management of blood cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines J Am Coll Cardiol 2019; 73(24): e285-e350. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2018.11.003. Erratum in Correction. J Am Coll Cardiol 2019; 73(24): 3237–3241. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2019.05.013>. Correction in: J Am Coll Cardiol 2024; 84(18): 1772. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2024.09.026>.
  27. Pearson GJ, Thanassoulis G, Anderson TJ et al. 2021 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia. Can J Cardiol 2021; 37(8): 1129–1150. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cjca.2021.03.016>.
  28. Cho L, Nicholls SJ, Nordestgaard BG et al. Design and rationale of the Lp(a)HORIZON trial. Am Heart J 2025; 287 : 1–9. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ahj.2025.03.019>.
  29. Amarenco P, Bogousslavsky J, Callahan A et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355(6): 549–559. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa061894>. Erratum in: N Engl J Med 2018; 378(25): 2450. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMx180019>.
  30. Boden WE, Probstfield JL, Anderson T et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med 2011; 365(24): 2255–2267. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1107579>. Erratum in: N Engl J Med 2012; 367(2): 189.
  31. Landray MJ, Haynes R, Hopewell JC et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371(3): 203–212. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1300955>.
  32. Sabatine MS, Giugliano RP, Keech AC et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017; 376(18): 1713–1722. Dostupné z DOI: <http://10.1056/NEJMoa1615664>.
  33. Schwartz GG, Steg PG, Szarek M et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018; 379(22): 2097–2107. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1801174>.
  34. Nissen SE, Ni W, Shen X et al. Lepodisiran, a long-duration small interfering RNA targeting lipoprotein(a). N Engl J Med 2025; 392(17): 1673–1683. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2415818>.
  35. Nissen SE, Lincoff AM, Brennan D et al. Zerlasiran for elevated lipoprotein(a): a randomized clinical trial. JAMA 2024; 332(2): 1717–1727. Dostupné z DOI: <http://doi:10.1001/jama.2024.21957>.
  36. Nicholls SJ, Ni W, Rhodes GM et al. Oral muvalaplin for lowering of lipoprotein(a): a randomized clinical trial. JAMA 2025; 333(3): 222–231. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2024.24017>.
  37. Blumenthal RS, Morris PB, Gaudino M et al. 2026 ACC/AHA multisociety 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. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2025.11.016>.
  38. Vyhláška č. 403/2025 Sb., kterou se mění vyhláška č. 70/2012 Sb., o preventivních prohlídkách. Účinnost od 1. 1. 2026. Dostupné z WWW: <https://www.sagit.cz/info/sb25403>.
  39. ClinicalTrials.gov. NCT04023552: Lp(a)HORIZON –⁠ pelacarsen. [01–08–2026].
  40. ClinicalTrials.gov. NCT05581303: OCEAN(a)-Outcomes –⁠ olpasiran. [01–08–2026].
  41. ClinicalTrials.gov. NCT06292013: ACCLAIM-Lp(a) –⁠ lepodisiran. [01–08–2026].
  42. ClinicalTrials.gov. NCT07157774: MOVE-Lp(a) –⁠ muvalaplin. [01–08–2026].
  43. ClinicalTrials.gov. NCT07136012: OCEAN(a)-PreEvent –⁠ olpasiran. [01–08–2026].
  44. Daghlas I, Georgakis MK, Arsenault BJ et al. Genetically predicted levels of lipoprotein(a) and risk of cerebrovascular disease. J Am Heart Assoc 2026; 15(3): e045423. Dostupné z DOI: <http://dx.doi.org/10.1161/JAHA.125.045423>.
  45. O’Donoghue ML, Fazio S, Giugliano RP et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation 2019; 139(12): 1483–1492. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037184>.
  46. Bittner VA, Szarek M, Aylward PE et al. [ODYSSEY OUTCOMES Committees and Investigators]. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol 2020; 75(2): 133–144. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2019.10.057>.
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