medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-115medsovet-8280Research ArticleДИСЛИПИДЕМИЯDISLIPIDEMIAСовременные тенденции решения проблемы резидуального сердечно-сосудистого рискаCurrent trends in solving the problem of residual cardiovascular riskhttps://orcid.org/0000-0003-2072-5511ОбъедковаН. Ю.ObedkovaN. Yu.

Наталья Юрьевна Объедкова, ассистент кафедры поликлинической терапии и общей врачебной практики

305041, Курск, ул. К. Маркса, д. 3

Natal’ja Yu. Obedkova, Assistant of the Department of Polyclinic Therapy and General Medical Practice

3, K. Marx St., Kursk, 305041

obedkovany@kursksmu.nethttps://orcid.org/0009-0005-7846-7801ГусляковаА. А.GuslyakovaA. A.

Анастасия Андреевна Гуслякова, студент

305041, Курск, ул. К. Маркса, д. 3

Anastasiya A. Guslyakova, Student

3, K. Marx St., Kursk, 305041

 

guslyakova.a@mail.ruhttps://orcid.org/0000-0003-1712-5005МальГ. С.MalG. S.

Галина Сергеевна Маль, д.м.н., профессор, заведующий кафедрой фармакологии

305041, Курск, ул. К. Маркса, д. 3

Galina S. Mal, Dr. Sci. (Med.), Professor, Head of the Department of Pharmacology

3, K. Marx St., Kursk, 305041

 

malgs@kursksmu.nethttps://orcid.org/0000-0003-0566-1476ОбъедковЕ. Г.ObedkovE. G.

Евгений Геннадьевич Объедков, к.м.н., доцент кафедры хирургических болезней № 1

305041, Курск, ул. К. Маркса, д. 3

Evgenij G. Obedkov, Cand. Sci. (Med.), Associate Professor of the Department of Surgical Diseases №1

3, K. Marx St., Kursk, 305041

 

obiedkoveg@kursksmu.netКурский государственный медицинский университетРоссияKursk State Medical UniversityRussian Federation20241905202406155163Copyright © Объедкова Н.Ю., Гуслякова А.А., Маль Г.С., Объедков Е.Г., 20242024Объедкова Н.Ю., Гуслякова А.А., Маль Г.С., Объедков Е.Г.Obedkova N.Y., Guslyakova A.A., Mal G.S., Obedkov E.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8280

Смертность от сердечно-сосудистых заболеваний является актуальной проблемой здравоохранения не только в Российской Федерации, но и во всем мире. У пациентов очень высокого риска, страдающих ишемической болезнью сердца и сопутствующими дислипидемиями, при достигнутых целевых уровнях атерогенных фракций липопротеинов, несмотря на достаточно эффективную многокомпонентную гиполипидемическую терапию, сохраняется высокий остаточный (резидуальный) риск развития сердечно-сосудистых осложнений – таких как нестабильная стенокардия, инфаркт миокарда, инсульт. В данной статье проводится обзор актуальной научной литературы, метаанализов исследований, рандомизированных клинических испытаний различных классов гиполипидемических лекарственных препаратов, рассматриваются основные причины сохранения резидуального риска сердечно-сосудистых осложнений, оценивается роль известных клинико-диагностических маркеров в его развитии, среди которых выделяются уровень липопротеина (а), триглицеридов и атерогенных липопротеинов, сохраняющееся асептическое воспаление сосудистой стенки, маркерами которого являются высокочувствительный С-реактивный белок, интерлейкин-6, интерлейкин-1β. Обсуждаются возможные терапевтические стратегии снижения резидуального риска у пациентов в зависимости от этиологического фактора, оцениваются эффективность омега-3 полиненасыщенных жирных кислот, фибратов, варианты использования РНК интерференции с помощью малых интерферирующих РНК и антисмысловых олигонуклеотидов, афереза липопротеинов, а также противовоспалительная терапия с использованием колхицина, малых доз метотрексата и моноклональных антител, ингибирующих продукцию провоспалительных интерлейкинов, в снижении резидуального сердечно-сосудистого риска. Оценка остаточного сердечно-сосудистого риска у пациента в клинической практике позволяет определить недостаточность или неэффективность проводимых мероприятий вторичной профилактики и выбрать иную, более современную или комплексную, тактику снижения сердечно-сосудистого риска.

Cardiovascular mortality is an urgent health problem not only in the Russian Federation, but also throughout the world. Patients of high cardiovascular risk, which suffering from ischemic heart disease and attending dyslipidemia, remain with high residual risk of cardiovascular complications such as unstable angina, myocardial infarction, stroke even in the case of achieved target level of atherogenic lipoproteins, no matter effective multicomponent hypolipidemic therapy. This article reviews the relevant scientific literature, meta-analyses of studies, randomized clinical trials of lipid-lowering drugs, examines the main reasons for the persistence of residual cardiovascular risk, evaluates the role of each clinical diagnostic marker in its progression, among which are the level of lipoprotein (a), triglycerides and other atherogenic lipoproteins, persistent aseptic inflammation of the vascular wall, the markers of which are highly sensitive C-reactive protein, interleukin-6, interleukin-1β. Possible therapeutic strategies for reducing residual risk depending on the etiological factor are discussed including the effectiveness in reducing residual cardiovascular risk with omega-3 polyunsaturated fatty acids, fibrates, options for RNA interference with small interfering RNA and antisense oligonucleotides usage, lipoprotein apheresis, as well as anti-inflammatory therapy using colchicine, low doses of methotrexate and monoclonal antibodies that inhibit the production of proinflammatory interleukins. Assessing a patient’s residual risk in clinical practice allows us to determine the insufficiency or ineffectiveness of secondary prevention measures and choose a different, more modern or comprehensive tactic for cardiovascular risk reducing.

резидуальный рискишемическая болезнь сердцадислипидемиягиполипидемическая терапиястатиныэзетимибиPCSK9омега-3 ПНЖКresidual riskcoronary heart diseasedyslipidemialipid-lowering therapystatinsezetimibeiPCSK9omega 3 polyunsaturated fatty acidsReferencesЕжов МВ, Кухарчук ВВ, Сергиенко ИВ, Алиева АС, Анциферов МБ, Аншелес АА. и др. Нарушения липидного обмена. Клинические рекомендации 2023. Российский кардиологический журнал. 2023;28(5):5471. https://doi.org/10.15829/1560-4071-2023-5471.Ezhov MV, Kukharchuk VV, Sergienko IV, Alieva AS, Antsiferov MB, Ansheles AA et al. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471. (In Russ.) https://doi.org/10.15829/1560-4071-2023-5471.Берштейн ЛЛ. Новые возможности снижения резидуального риска при ишемической болезни сердца. Кардиология. 2020;60(11):110–116. https://doi.org/10.18087/cardio.2020.11.n1370.Bershtein LL. New Possibilities to Reduce the Residual Risk in Patients with Ischemic Heart Disease. Kardiologiya. 2020;60(11):110–116. (In Russ.) https://doi.org/10.18087/cardio.2020.11.n1370.Yanai H, Adachi H, Hakoshima M, Katsuyama H. Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk. Int J Mol Sci. 2022;23(21):13499. https://doi.org/10.3390/ijms232113499.Yanai H, Adachi H, Hakoshima M, Katsuyama H. Atherogenic Lipoproteins for the Statin Residual Cardiovascular Disease Risk. Int J Mol Sci. 2022;23(21):13499. https://doi.org/10.3390/ijms232113499.Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. https://doi.org/10.1093/eurheartj/ehz455.Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. https://doi.org/10.1093/eurheartj/ehz455.Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. https://doi.org/10.1161/CIR.0000000000000625.Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-e1143. https://doi.org/10.1161/CIR.0000000000000625.Wang Z, Zhai X, Xue M, Cheng W, Hu H. Prognostic value of lipoprotein (a) level in patients with coronary artery disease: a meta-analysis. Lipids Health Dis. 2019;18(1):150. https://doi.org/10.1186/s12944-019-1092-6.Wang Z, Zhai X, Xue M, Cheng W, Hu H. Prognostic value of lipoprotein (a) level in patients with coronary artery disease: a meta-analysis. Lipids Health Dis. 2019;18(1):150. https://doi.org/10.1186/s12944-019-1092-6.Matsushita K, Hibi K, Komura N, Kimura Y, Matsuzawa Y, Konishi M et al. Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy. J Cardiol. 2020;76(1):66–72. https://doi.org/10.1016/j.jjcc.2020.01.005.Matsushita K, Hibi K, Komura N, Kimura Y, Matsuzawa Y, Konishi M et al. Impact of serum lipoprotein (a) level on coronary plaque progression and cardiovascular events in statin-treated patients with acute coronary syndrome: a yokohama-acs substudy. J Cardiol. 2020;76(1):66–72. https://doi.org/10.1016/j.jjcc.2020.01.005.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. https://doi.org/10.1093/eurjpc/zwab171.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. https://doi.org/10.1093/eurjpc/zwab171.Tsimikas S, Gordts PLSM, Nora C, Yeang C, Witztum JL. Statin therapy increases lipoprotein(a) levels. Eur Heart J. 2020;41(24):2275–2284. https://doi.org/10.1093/eurheartj/ehz310.Tsimikas S, Gordts PLSM, Nora C, Yeang C, Witztum JL. Statin therapy increases lipoprotein(a) levels. Eur Heart J. 2020;41(24):2275–2284. https://doi.org/10.1093/eurheartj/ehz310.Sahebkar A, Simental-Mendía LE, Pirro M, Banach M, Watts GF, Sirtori C et al. Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials. Sci Rep. 2018;8(1):17887. https://doi.org/10.1038/s41598-018-36204-7.Sahebkar A, Simental-Mendía LE, Pirro M, Banach M, Watts GF, Sirtori C et al. Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials. Sci Rep. 2018;8(1):17887. https://doi.org/10.1038/s41598-018-36204-7.Schwartz GG, Szarek M, Bittner VA, Diaz R, Goodman SG, Jukema JW et al. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. J Am Coll Cardiol. 2021;78(5):421–433. https://doi.org/10.1016/j.jacc.2021.04.102.Schwartz GG, Szarek M, Bittner VA, Diaz R, Goodman SG, Jukema JW et al. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol. J Am Coll Cardiol. 2021;78(5):421–433. https://doi.org/10.1016/j.jacc.2021.04.102.Swerdlow DI, Rider DA, Yavari A, Wikström Lindholm M, Campion GV, Nissen SE. Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics. Cardiovasc Res. 2022;118(5):1218–1231. https://doi.org/10.1093/cvr/cvab100.Swerdlow DI, Rider DA, Yavari A, Wikström Lindholm M, Campion GV, Nissen SE. Treatment and prevention of lipoprotein(a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics. Cardiovasc Res. 2022;118(5):1218–1231. https://doi.org/10.1093/cvr/cvab100.Raina R, Young C, Krishnappa V, Chanchlani R. Role of Lipoprotein Apheresis in Cardiovascular Disease Risk Reduction. Blood Purif. 2019;47(4):301–316. https://doi.org/10.1159/000497447.Raina R, Young C, Krishnappa V, Chanchlani R. Role of Lipoprotein Apheresis in Cardiovascular Disease Risk Reduction. Blood Purif. 2019;47(4):301–316. https://doi.org/10.1159/000497447.Schettler VJJ, Neumann CL, Peter C, Zimmermann T, Julius U, Hohenstein B et al. Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels. Clin Res Cardiol Suppl. 2019;14(Suppl 1):33–38. https://doi.org/10.1007/s11789-019-00094-4.Schettler VJJ, Neumann CL, Peter C, Zimmermann T, Julius U, Hohenstein B et al. Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels. Clin Res Cardiol Suppl. 2019;14(Suppl 1):33–38. https://doi.org/10.1007/s11789-019-00094-4.Parhofer KG. Apheresis: What Should a Clinician Know? Curr Atheroscler Rep. 2023;25(3):77–83. https://doi.org/10.1007/s11883-023-01081-7.Parhofer KG. Apheresis: What Should a Clinician Know? Curr Atheroscler Rep. 2023;25(3):77–83. https://doi.org/10.1007/s11883-023-01081-7.Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, Averna M et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021;42(47):4791–4806. https://doi.org/10.1093/eurheartj/ehab551.Ginsberg HN, Packard CJ, Chapman MJ, Borén J, Aguilar-Salinas CA, Averna M et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 2021;42(47):4791–4806. https://doi.org/10.1093/eurheartj/ehab551.Уткина ЕА, Афанасьева ОИ, Покровский СН. Гетерогенность липопротеидов и их роль в развитии сердечно-сосудистых заболеваний. Российский кардиологический журнал. 2019;(5):82–89. Режим доступа: https://russjcardiol.elpub.ru/jour/article/view/3320?locale=ru_RU.Utkina EA, Afanasieva OI, Pokrovsky SN. The heterogeneity of lipoproteins and their role in the development of cardiovascular diseases. Russian Journal of Cardiology. 2019;(5):82–89. (In Russ.) Available at: https://russjcardiol.elpub.ru/jour/article/view/3320?locale=ru_RU.Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG. Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study. Diabetologia. 2023;66(12):2238–2249. https://doi.org/10.1007/s00125-023-06016-0.Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG. Elevated remnant cholesterol and atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study. Diabetologia. 2023;66(12):2238–2249. https://doi.org/10.1007/s00125-023-06016-0.Delialis D, Georgiopoulos G, Aivalioti E, Konstantaki C, Oikonomou E, Bampatsias D et al. Remnant cholesterol in atherosclerotic cardiovascular disease: A systematic review and meta-analysis. Hellenic J Cardiol. 2023;74:48–57. https://doi.org/10.1016/j.hjc.2023.04.007.Delialis D, Georgiopoulos G, Aivalioti E, Konstantaki C, Oikonomou E, Bampatsias D et al. Remnant cholesterol in atherosclerotic cardiovascular disease: A systematic review and meta-analysis. Hellenic J Cardiol. 2023;74:48–57. https://doi.org/10.1016/j.hjc.2023.04.007.Nelson AJ, Navar AM, Mulder H, Wojdyla D, Philip S, Granowitz C et al. Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial). Am J Cardiol. 2020;132:36–43. https://doi.org/10.1016/j.amjcard.2020.07.005.Nelson AJ, Navar AM, Mulder H, Wojdyla D, Philip S, Granowitz C et al. Association Between Triglycerides and Residual Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease (From the Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D] Trial). Am J Cardiol. 2020;132:36–43. https://doi.org/10.1016/j.amjcard.2020.07.005.Yang J, Wang Y, Xi Z, Ma Y, Shao C, Wang W, Tang YD. Remnant-Like Particle Cholesterol and the Risk of Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis. 2022;9(12):452. https://doi.org/10.3390/jcdd9120452.Yang J, Wang Y, Xi Z, Ma Y, Shao C, Wang W, Tang YD. Remnant-Like Particle Cholesterol and the Risk of Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis. J Cardiovasc Dev Dis. 2022;9(12):452. https://doi.org/10.3390/jcdd9120452.Fujihara Y, Nakamura T, Horikoshi T, Obata JE, Fujioka D, Watanabe Y et al. Remnant Lipoproteins Are Residual Risk Factor for Future Cardiovascular Events in Patients With Stable Coronary Artery Disease and On-Statin Low-Density Lipoprotein Cholesterol Levels <70 mg/dL. Circ J. 2019;83(6):1302–1308. https://doi.org/10.1253/circj.CJ-19-0047.Fujihara Y, Nakamura T, Horikoshi T, Obata JE, Fujioka D, Watanabe Y et al. Remnant Lipoproteins Are Residual Risk Factor for Future Cardiovascular Events in Patients With Stable Coronary Artery Disease and On-Statin Low-Density Lipoprotein Cholesterol Levels <70 mg/dL. Circ J. 2019;83(6):1302–1308. https://doi.org/10.1253/circj.CJ-19-0047.Shao Q, Yang Z, Wang Y, Li Q, Han K, Liang J et al. Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome. J Atheroscler Thromb. 2022;29(12):1808–1822. https://doi.org/10.5551/jat.63397.Shao Q, Yang Z, Wang Y, Li Q, Han K, Liang J et al. Elevated Remnant Cholesterol is Associated with Adverse Cardiovascular Outcomes in Patients with Acute Coronary Syndrome. J Atheroscler Thromb. 2022;29(12):1808–1822. https://doi.org/10.5551/jat.63397.Cao YX, Zhang HW, Jin JL, Liu HH, Zhang Y, Gao Y et al. The longitudinal association of remnant cholesterol with cardiovascular outcomes in patients with diabetes and pre-diabetes. Cardiovasc Diabetol. 2020;19(1):104. https://doi.org/10.1186/s12933-020-01076-7.Cao YX, Zhang HW, Jin JL, Liu HH, Zhang Y, Gao Y et al. The longitudinal association of remnant cholesterol with cardiovascular outcomes in patients with diabetes and pre-diabetes. Cardiovasc Diabetol. 2020;19(1):104. https://doi.org/10.1186/s12933-020-01076-7.Сусеков АВ. Фенофибрат при лечении больных с гипертриглицеридемиями и атеросклерозом: новые данные. Лечебное дело. 2020;(1):24–37. https://doi.org/10.24411/2071-5315-2020-12189.Susekov AV. Fenofibrate in the treatment of patients with hypertriglyceridemia and atherosclerosis: new data. Lechebnoe Delo. 2020;(1):24–37. https://doi.org/10.24411/2071-5315-2020-12189.Объедкова НЮ, Маль ГС, Селихова ЕМ, Объедков ЕГ. Прогрессирование гиперлипидемии как результат перенесенной новой коронавирусной инфекции у больных ишемической болезнью сердца. Innova. 2023;9(2):59–62. Режим доступа: https://www.innova-journal.ru/jour/article/view/405.Obedkova NYu, Mal GS, Selikhova EM, Obedkov EG. Progression of hyperlipidemia as a result of a new coronavirus infection in patients with coronary heart disease. Innova. 2023;9(2):59–62. (In Russ.) Available at: https://www.innova-journal.ru/jour/article/view/405.Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19(1):28. https://doi.org/10.1186/s12933-020-01002-x.Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19(1):28. https://doi.org/10.1186/s12933-020-01002-x.Pradhan AD, Paynter NP, Everett BM, Glynn RJ, Amarenco P, Elam M et al. Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. Am Heart J. 2018;206:80–93. https://doi.org/10.1016/j.ahj.2018.09.011.Pradhan AD, Paynter NP, Everett BM, Glynn RJ, Amarenco P, Elam M et al. Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. Am Heart J. 2018;206:80–93. https://doi.org/10.1016/j.ahj.2018.09.011.Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022;387(21):1923–1934. https://doi.org/10.1056/NEJMoa2210645.Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022;387(21):1923–1934. https://doi.org/10.1056/NEJMoa2210645.Кытикова ОЮ, Новгородцева ТП, Денисенко ЮК, Антонюк МВ, Гвозденко ТА. Омега-3 полиненасыщенные жирные кислоты в коррекции дислипидемии и снижении остаточного риска сердечно-сосудистых заболеваний. Бюллетень физиологии и патологии дыхания. 2023;(87):124–137. https://doi.org/10.36604/1998-5029-2023-87-124-137.Kytikova OY, Novgorodtseva TP, Denisenko YK, Antonyuk MV, Gvozdenko TA. Omega-3 polyunsaturated fatty acids for the management of dyslipidemia and reduction of residual cardiovascular risk. Bulletin Physiology and Pathology of Respiration. 2023;(87):124–137. (In Russ.) https://doi.org/10.36604/1998-5029-2023-87-124-137.Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. https://doi.org/10.1056/NEJMoa1812792.Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. https://doi.org/10.1056/NEJMoa1812792.Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540–1550. https://doi.org/10.1056/NEJMoa1804989.Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540–1550. https://doi.org/10.1056/NEJMoa1804989.Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23–32. https://doi.org/10.1056/NEJMoa1811403.Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23–32. https://doi.org/10.1056/NEJMoa1811403.Perez-Martinez P, Katsiki N, Mikhailidis DP. The Role of n-3 Fatty Acids in Cardiovascular Disease: Back to the Future. Angiology. 2020;71(1):10–16. https://doi.org/10.1177/0003319719842005.Perez-Martinez P, Katsiki N, Mikhailidis DP. The Role of n-3 Fatty Acids in Cardiovascular Disease: Back to the Future. Angiology. 2020;71(1):10–16. https://doi.org/10.1177/0003319719842005.Jun JE, Jeong IK, Yu JM, Kim SR, Lee IK, Han KA et al. Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Diabetes Metab J. 2020;44(1):78–90. https://doi.org/10.4093/dmj.2018.0265.Jun JE, Jeong IK, Yu JM, Kim SR, Lee IK, Han KA et al. Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Diabetes Metab J. 2020;44(1):78–90. https://doi.org/10.4093/dmj.2018.0265.Morise AP, Tennant J, Holmes SD, Tacker DH. The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Nonfasting Remnant Cholesterol in a Real World Population. J Lipids. 2018;2018:9194736. https://doi.org/10.1155/2018/9194736.Morise AP, Tennant J, Holmes SD, Tacker DH. The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Nonfasting Remnant Cholesterol in a Real World Population. J Lipids. 2018;2018:9194736. https://doi.org/10.1155/2018/9194736.Ray KK, Kallend D, Leiter LA, Raal FJ, Koenig W, Jaros MJ et al. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J. 2022;43(48):5047–5057. https://doi.org/10.1093/eurheartj/ehac615.Ray KK, Kallend D, Leiter LA, Raal FJ, Koenig W, Jaros MJ et al. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J. 2022;43(48):5047–5057. https://doi.org/10.1093/eurheartj/ehac615.Bergmark BA, Marston NA, Bramson CR, Curto M, Ramos V, Jevne A et al. Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70. Circulation. 2022;145(18):1377–1386. https://doi.org/10.1161/CIRCULATIONAHA.122.059266.Bergmark BA, Marston NA, Bramson CR, Curto M, Ramos V, Jevne A et al. Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70. Circulation. 2022;145(18):1377–1386. https://doi.org/10.1161/CIRCULATIONAHA.122.059266.Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR et al. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019;381(6):531–542. https://doi.org/10.1056/NEJMoa1715944.Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR et al. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Engl J Med. 2019;381(6):531–542. https://doi.org/10.1056/NEJMoa1715944.Lutgens E, Atzler D, Döring Y, Duchene J, Steffens S, Weber C. Immunotherapy for cardiovascular disease. Eur Heart J. 2019;40(48):3937–3946. https://doi.org/10.1093/eurheartj/ehz283.Lutgens E, Atzler D, Döring Y, Duchene J, Steffens S, Weber C. Immunotherapy for cardiovascular disease. Eur Heart J. 2019;40(48):3937–3946. https://doi.org/10.1093/eurheartj/ehz283.Ridker PM, MacFadyen JG, Glynn RJ, Bradwin G, Hasan AA, Rifai N. Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial. Eur Heart J. 2020;41(31):2952–2961. https://doi.org/10.1093/eurheartj/ehaa160.Ridker PM, MacFadyen JG, Glynn RJ, Bradwin G, Hasan AA, Rifai N. Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial. Eur Heart J. 2020;41(31):2952–2961. https://doi.org/10.1093/eurheartj/ehaa160.Ridker PM. Clinician’s Guide to Reducing Inflammation to Reduce Atherothrombotic Risk: JACC Review Topic of the Week. J Am Coll Cardiol. 2018;72(25):3320–3331. https://doi.org/10.1016/j.jacc.2018.06.082.Ridker PM. Clinician’s Guide to Reducing Inflammation to Reduce Atherothrombotic Risk: JACC Review Topic of the Week. J Am Coll Cardiol. 2018;72(25):3320–3331. https://doi.org/10.1016/j.jacc.2018.06.082.Liu HH, Guo YL, Zhu CG, Wu NQ, Gao Y, Xu RX et al. Synergistic effect of the commonest residual risk factors, remnant cholesterol, lipoprotein(a), and inflammation, on prognosis of statin-treated patients with chronic coronary syndrome. J Transl Med. 2022;20(1):243. https://doi.org/10.1186/s12967-022-03448-x.Liu HH, Guo YL, Zhu CG, Wu NQ, Gao Y, Xu RX et al. Synergistic effect of the commonest residual risk factors, remnant cholesterol, lipoprotein(a), and inflammation, on prognosis of statin-treated patients with chronic coronary syndrome. J Transl Med. 2022;20(1):243. https://doi.org/10.1186/s12967-022-03448-x.Bohula EA, Giugliano RP, Leiter LA, Verma S, Park JG, Sever PS et al. Inflammatory and Cholesterol Risk in the FOURIER Trial. Circulation. 2018;138(2):131–140. https://doi.org/10.1161/CIRCULATIONAHA.118.034032.Bohula EA, Giugliano RP, Leiter LA, Verma S, Park JG, Sever PS et al. Inflammatory and Cholesterol Risk in the FOURIER Trial. Circulation. 2018;138(2):131–140. https://doi.org/10.1161/CIRCULATIONAHA.118.034032.Pradhan AD, Aday AW, Rose LM, Ridker PM. Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy. Circulation. 2018;138(2):141–149. https://doi.org/10.1161/CIRCULATIONAHA.118.034645.Pradhan AD, Aday AW, Rose LM, Ridker PM. Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy. Circulation. 2018;138(2):141–149. https://doi.org/10.1161/CIRCULATIONAHA.118.034645.Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497–2505. https://doi.org/10.1056/NEJMoa1912388.Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019;381(26):2497–2505. https://doi.org/10.1056/NEJMoa1912388.Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41(42):4092–4099. https://doi.org/10.1093/eurheartj/ehaa659.Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R et al. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020;41(42):4092–4099. https://doi.org/10.1093/eurheartj/ehaa659.Ridker PM, Libby P, MacFadyen JG, Thuren T, Ballantyne C, Fonseca F et al. Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J. 2018;39(38):3499–3507. https://doi.org/10.1093/eurheartj/ehy310.Ridker PM, Libby P, MacFadyen JG, Thuren T, Ballantyne C, Fonseca F et al. Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS). Eur Heart J. 2018;39(38):3499–3507. https://doi.org/10.1093/eurheartj/ehy310.Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2020;41(23):2153–2163. https://doi.org/10.1093/eurheartj/ehz542.Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2020;41(23):2153–2163. https://doi.org/10.1093/eurheartj/ehz542.Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380(8):752–762. https://doi.org/10.1056/NEJMoa1809798.Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380(8):752–762. https://doi.org/10.1056/NEJMoa1809798.

The authors declare that there are no conflicts of interest present.