
Липопротеин(а) и цереброваскулярные заболевания
Журнал: Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2026;126(3-2):5-11.
DOI: 10.17116/jnevro20261260325
Прочитано: 1185 раз
Резюме
Липопротеин(а) представляет собой генетически регулируемую липопротеиноподобную частицу низкой плотности, которая привлекает все большее внимание как независимый патогенный фактор риска развития сосудистой патологии. Накопление данных эпидемиологических, генетических исследований, а также исследований, направленных на выяснение патогенетических механизмов, подтвердило многогранную роль липопротеина(а) в развитии атерогенеза, сосудистой кальцификации, воспаления и тромбогенеза в различных сосудистых бассейнах. Повышенный уровень липопротеина(а) связан с повышенным риском сердечно-сосудистых и цереброваскулярных событий, даже после контроля традиционных факторов риска. Повышенный уровень липопротеина(а) связан с увеличением рецидивов инсульта и плохим функциональным исходом у пациентов с инсультом. Липопротеин(а) может представлять собой новую терапевтическую мишень для вторичной профилактики инсульта в дополнение к многообещающему биомаркеру.
Ключевые слова
- липопротеин(а)
- каротидный атеросклероз
- ишемический инсульт
- функциональные исходы
- терапевтические подходы
Дата поступления: 01.11.2025
Дата принятия в печать: 11.12.2025
Дата публикации: 06.04.2026
- Jawi MM, Frohlich J, Chan SY. Lipoprotein(a) the insurgent: a new insight into the structure, function, metabolism, pathogenicity, and medications affecting lipoprotein(a) molecule. J Lipids. 2020;2020:3491764. https://doi.org/10.1155/2020/3491764
- Vinci P, Di Girolamo FG, Panizon E, et al. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. Int J Environ Res Public Health. 2023;20(18):6721. https://doi.org/10.3390/ijerph20186721
- Kronenberg F. Human genetics and the causal role of lipoprotein(a) for various diseases. Cardiovasc Drugs Ther. 2016;30:87-100. https://doi.org/10.1007/s10557-016-6648-3
- Tsimikas S. A Test in Context: Lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69:692-711. https://doi.org/10.1016/j.jacc.2016.11.042
- Nicholls SJ, Nissen SE, Fleming C, et al. Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial. JAMA. 2023;330(11):1042-53. https://doi.org/10.1001/jama.2023.16503
- Enkhmaa B, Berglund L. Non-genetic influences on lipoprotein(a) concentrations. Atherosclerosis. 2022;349:53-62. https://doi.org/10.1016/j.atherosclerosis.2022.04.006
- Kosmas CE, Bousvarou MD, Papakonstantinou EJ, et al. Lipoprotein (a) and cerebrovascular disease. J Int Med Res. 2024;52(7):3000605241264182. https://doi.org/10.1177/03000605241264182
- Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: Mechanistic insights from animal models. Clin Biochem. 2004;37:333-343. https://doi.org/10.1016/j.clinbiochem.2003.12.007
- Deb A, Caplice NM. Lipoprotein(a): New insights into mechanisms of atherogenesis and thrombosis. Clin Cardiol. 2004;27:258-264. https://doi.org/10.1002/clc.4960270503
- Kapetanopoulos A, Fresser F, Millonig G, et al. Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain. Mol Genet Genom. 2002;267:440-446. https://doi.org/10.1007/s00438-002-0673-6
- Boffa MB, Koschinsky ML. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease. Nat Rev Cardiol. 2019;16:305-318. https://doi.org/10.1038/s41569-018-0153-2
- Nielsen LB, Nordestgaard BG, Stender S, et al. Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 1995;15:1492-1502. https://doi.org/10.1161/01.ATV.15.9.1492
- 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;71:177-192. https://doi.org/10.1016/j.jacc.2017.11.014
- Song P, Fang Z, Wang H, et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: A systematic review, meta-analysis, and modelling study. Lancet Glob Health. 2020;8:e721-e729. https://doi.org/10.1016/S2214-109X(20)30117-0
- Lampsas S, Xenou M, Oikonomou E, et al. Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment. Molecules. 2023;28:969. https://doi.org/10.3390/molecules28030969
- Klein JH, Hegele RA, Hackam DG, et al. Lipoprotein(a) is associated differentially with carotid stenosis, occlusion, and total plaque area. Arterioscler Thromb Vasc Biol. 2008;28:1851-1856. https://doi.org/10.1161/ATVBAHA.108.169292
- Steffen BT, Thanassoulis G, Duprez D, et al. Race-Based Differences in Lipoprotein(a)-Associated Risk of Carotid Atherosclerosis. Arterioscler Thromb Vasc Biol. 2019;39:523-529. https://doi.org/10.1161/ATVBAHA.118.312267
- Tsioulos G, Kounatidis D, Vallianou NG, et al. Lipoprotein(a) and Atherosclerotic Cardiovascular Disease: Where Do We Stand? Int J Mol Sci. 2024;25(6):3537. https://doi.org/10.3390/ijms25063537
- França V, Gomes ÉIL, de Campos EVS, et al. Relationship between lipoprotein (a) and subclinical carotid atherosclerosis in asymptomatic individuals. Clinics. 2022;77:100107. https://doi.org/10.1016/j.clinsp.2022.100107
- Lin L, Deng KQ, Chen Z, et al. Lipoprotein(a) distribution and its association with carotid arteriopathy in the Chinese population. Atherosclerosis. 2023;372:1-9. https://doi.org/10.1016/j.atherosclerosis.2023.03.007
- Nasr N, Ruidavets JB, Farghali A, et al. Lipoprotein (a) and carotid atherosclerosis in young patients with stroke. Stroke. 2011;42:3616-3618. https://doi.org/10.1161/STROKEAHA.111.624684
- Zhao XQ, Hatsukami TS, Hippe DS, et al. Clinical factors associated with high-risk carotid plaque features as assessed by magnetic resonance imaging in patients with established vascular disease (from the AIM-HIGH Study). Am J Cardiol. 2014;114:1412-1419. https://doi.org/10.1016/j.amjcard.2014.08.001
- Xia S, Qiu W, Cai A, et al. The Association of Lipoprotein(a) and Intraplaque Neovascularization in Patients with Carotid Stenosis: A Retrospective Study. BMC Cardiovasc. Disord. 2021;21:285. https://doi.org/10.1186/s12872-021-02038-x
- Schreiner PJ, Heiss G, Tyroler HA, et al. Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol. 1996;16:471-478. https://doi.org/10.1161/01.ATV.16.3.471
- Van Dam-Nolen DHK, van Dijk AC, Crombag G, et al. Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study. Atherosclerosis. 2021;329:22-29. https://doi.org/10.1016/j.atherosclerosis.2021.06.004
- Zenker G, Koltringer P, Bone G, et al. Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke. 1986;17:942-945. https://doi.org/10.1161/01.STR.17.5.942
- Langsted A, Nordestgaard BG, Kamstrup PR. Elevated Lipoprotein(a) and Risk of Ischemic Stroke. J Am Coll Cardiol. 2019;74:54-66. https://doi.org/10.1016/j.jacc.2019.03.524
- Arora P, Kalra R, Callas PW, et al. Lipoprotein(a) and Risk of Ischemic Stroke in the REGARDS Study. Arterioscler Thromb Vasc Biol. 2019;39:810-818. https://doi.org/10.1161/ATVBAHA.118.311857
- Ohira T, Schreiner PJ, Morrisett JD, et al. Lipoprotein(a) and Incident Ischemic Stroke. Stroke. 2006;37:1407-1412. https://doi.org/10.1161/01.STR.0000222666.21482.b6
- Huang Y, Zhang R, Han L, et al. Lipoprotein(a) and Stroke: A Two-Sample Mendelian Randomization Study. Front Aging Neurosci. 2023;15:1178079. https://doi.org/10.3389/fnagi.2023.1178079
- 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;11:15660. https://doi.org/10.1038/s41598-021-95141-0
- Lackova A, Gdovinova Z, Kozarova M, et al. Lipoprotein(a) Concentration as a Risk Factor for Ischaemic Stroke and Its Subtypes. Neurol I Neurochir Pol. 2024;58:316-322. https://doi.org/10.5603/pjnns.98343
- Koh MY, Toh KZ, Loh ED, et al. Association of elevated lipoprotein(a) levels with ischemic stroke in young patients — a systematic review and meta-analysis. J Stroke Cerebrovasc Dis. 2024;33(11):107960. https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.107960
- Aronis KN, Zhao D, Hoogeveen RC, et al. Associations of Lipoprotein(a) Levels with Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc. 2017;6:e007372. https://doi.org/10.1161/JAHA.117.007372
- Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in Atherosclerotic Cardiovascular Disease and Aortic Stenosis: A European Atherosclerosis Society Consensus Statement. Eur Heart J. 2022;43:3925-3946. https://doi.org/10.1093/eurheartj/ehac361
- Mohammadi-Shemirani P, Chong M, Narula S, et al. Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study. J Am Coll Cardiol. 2022;79:1579-1590. https://doi.org/10.1016/j.jacc.2022.02.018
- Hu J, Lei H, Liu L, et al. Lipoprotein(a), a Lethal Player in Calcific Aortic Valve Disease. Front Cell Dev Biol. 2022;10:812368. https://doi.org/10.3389/fcell.2022.812368
- Lisi M, Pastore MC, Fiorio A, et al. Left Atrial Remodeling in Response to Aortic Valve Replacement: Pathophysiology and Myocardial Strain Analysis. Life. 2022;12:2074. https://doi.org/10.3390/life12122074
- Song J, Zhang X, Wei M, et al. Association between Lipoprotein(a) and Thromboembolism in Patients with Non-Valvular Atrial Fibrillation: A Cross-Sectional Study. Lipids Health Dis. 2022;21:78. https://doi.org/10.1186/s12944-022-01682-2
- Chehab O, Abdollahi A, Whelton SP, et al. Association of Lipoprotein(a) Levels with Myocardial Fibrosis in the Multi-Ethnic Study of Atherosclerosis. J Am Coll Cardiol. 2023;82:2280-2291. https://doi.org/10.1016/j.jacc.2023.10.016
- Wang H, Zhao J, Gui Y, et al. Elevated lipoprotein (a) and risk of poor functional outcome in Chinese patients with ischemic stroke and type 2 diabetes. Neurotox Res. 2018;33:868-875. https://doi.org/10.1007/s12640-017-9850-6
- Zhang W, Zhang XA. Prognostic value of serum lipoprotein(a) levels in patients with acute ischemic stroke. NeuroReport. 2014;25:262-266. https://doi.org/10.1097/WNR.0000000000000094
- Chakraborty B, Vishnoi G, Goswami B, et al. Lipoprotein(a), ferritin, and albumin in acute phase reaction predicts severity and mortality of acute ischemic stroke in North Indian Patients. J Stroke Cerebrovasc Dis. 2013;22:e159-167. https://doi.org/10.1016/j.jstrokecerebrovasdis.2012.10.013
- Jiang X, Xu J, Hao X, et al. Elevated lipoprotein(a) and lipoprotein-associated phospholipase A2 are associated with unfavorable functional outcomes in patients with ischemic stroke. J Neuroinflammation. 2021;18(1):307. https://doi.org/10.1186/s12974-021-02359-w
- Dong W, Zhong X, Yuan K, et al. Lipoprotein(a) and Functional Outcome of Acute Ischemic Stroke When Discordant with Low-Density Lipoprotein Cholesterol. Postgrad Med J. 2023;99:1160-1166. https://doi.org/10.1093/postmj/qgad070
- Fu Y, Liu Q, Anrather J, et al. Immune interventions in stroke. Nat Rev Neurol. 2015;11:524-535. https://doi.org/10.1038/nrneurol.2015.144
- 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. https://doi.org/10.5853/jos.2024.04623
- 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. https://doi.org/10.57187/s.3633
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Eur Heart J. 2020;41:111-188. https://doi.org/10.1093/eurheartj/ehz455
- Tsimikas S, Gordts PLSM, Nora C, et al. Statin Therapy Increases Lipoprotein(a) Levels. Eur Heart J. 2020;41:2275-2284. https://doi.org/10.1093/eurheartj/ehz310
- Willeit P, Ridker PM, Nestel PJ, et al. Baseline and On-Statin Treatment Lipoprotein(a) Levels for Prediction of Cardiovascular Events: Individual Patient-Data Meta-Analysis of Statin Outcome Trials. Lancet. 2018;392:1311-1320. https://doi.org/10.1016/S0140-6736(18)31652-0
- Wang L, Liu L, Zhao Y, et al. Lipoprotein(a) and Residual Vascular Risk in Statin-Treated Patients with First Acute Ischemic Stroke: A Prospective Cohort Study. Front Neurol. 2022;13:1004264. https://doi.org/10.3389/fneur.2022.1004264
- Nicholls SJ. Therapeutic Potential of Lipoprotein(a) Inhibitors. Drugs. 2024;84:637-643. https://doi.org/10.1007/s40265-024-02046-z
- Farmakis I, Doundoulakis I, Pagiantza A, et al. Lipoprotein(a) Reduction with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Systematic Review and Meta-Analysis. J Cardiovasc Pharmacol. 2021;77:397. https://doi.org/10.1097/FJC.0000000000000963
- Jukema JW, Zijlstra LE, Bhatt DL, et al. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES. Circulation. 2019;140:2054-2062. https://doi.org/10.1161/CIRCULATIONAHA.119.043826
- Giugliano RP, Pedersen TR, Saver JL, et al. Stroke Prevention with the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients with Stable Atherosclerosis. Stroke. 2020;51:1546-1554. https://doi.org/10.1161/STROKEAHA.119.027759
- Reyes-Soffer G, Ginsberg HN, Berglund L, 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:e48-e60. https://doi.org/10.1161/ATV.0000000000000147
- Sahebkar A, Reiner Ž, Simental-Mendía LE, et al. Effect of Extended-Release Niacin on Plasma Lipoprotein(a) Levels: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Metab Clin Exp. 2016;65:1664-1678. https://doi.org/10.1016/j.metabol.2016.08.007
- Chasman DI, Shiffman D, Zee RYL, et al. Polymorphism in the Apolipoprotein(a) Gene, Plasma Lipoprotein(a), Cardiovascular Disease, and Low-Dose Aspirin Therapy. Atherosclerosis. 2009;203:371-376. https://doi.org/10.1016/j.atherosclerosis.2008.07.019
- Sosnowska B, Surma S, Banach M. Targeted treatment against lipoprotein (a): the coming breakthrough in lipid lowering therapy. Pharmaceuticals (Basel). 2022;15:1573. https://doi.org/10.3390/ph15121573
- Stankov S, Cuchel M. Gene editing for dyslipidemias: New tools to “cut” lipids. Atherosclerosis. 2023;368:14-24. https://doi.org/10.1016/j.atherosclerosis.2023.01.010
- Kronenberg F. Lipoprotein(a): from Causality to Treatment. Curr Atheroscler Rep. 2024;26(3):75-82. https://doi.org/10.1007/s11883-024-01187-6
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