Атеросклероз и воспаление – путь от патогенеза к терапии: обзор современного состояния проблемы (часть 2)

Достижения многочисленных исследований в изучении фундаментальных аспектов атеросклероза диктуют необходимость систематизации накопленных данных. Во второй части лекции представлен анализ роли ключевых механизмов реализации воспалительного процесса в развитии атеросклероза. Рассмотрена роль инфламмасомы, нарушений гемодинамики в сосудистой стенке, патологии vasa vasorum, дисфункции эндотелиоцитов, матриксных металлопротеиназ, сигнальных путей Notch и Wnt в атерогенезе, а также ассоциированные с атеросклерозом особенности патогенеза кальцификации сосудов.
Отдельным разделом представлен обзор современных фармакотерапевтических подходов к лечению атерогенной дислипидемии. Комплексный анализ современных представлений о патогенезе атеросклероза и перспективных методов лекарственной терапии позволит обозначить дальнейшие направления исследований в липидологии и вывести возможности профилактической кардиологии на потенциально новый уровень.

1. Бойцов С.А., Погосова Н.В., Аншелес А.А., Бадтиева В.А., Балахонова Т.В., Барбараш О.Л. и др. Кардиоваскулярная профилактика 2022. Российские национальные рекомендации. Российский кардиологический журнал. 2023;28(5):5452. DOI: 10.15829/1560-4071-2023-5452.

2. Погосова Н.В., Оганов Р.Г., Бойцов С.А., Аушева А.К., Соколова О.Ю., Курсаков А.А. и др. Анализ ключевых показателей вторичной профилактики у пациентов с ишемической болезнью сердца в России и Европе по результатам российской части международного многоцентрового исследования EUROASPIRE V. Кардиоваскулярная терапия и профилактика. 2020;19(6):2739.

3. Погосова Н.В., Бойцов С.А. Профилактическая кардиология 2024: состояние проблемы и перспективы развития. Кардиология. 2024;64(1):4–13. DOI: 10.18087/cardio.2024.1.n2636.

4. Погосова Н.В. Значимость кардиореабилитации в эпоху современного лечения сердечно-сосудистых заболеваний. Кардиология. 2022;62(4):3–11. DOI: 10.18087/cardio.2022.4.n2015.

5. Метельская В.А., Шальнова С.А., Деев А.Д., Перова Н.В., Гомыранова Н.В., Литинская О.А. и др. Анализ распространенности показателей, характеризующих атерогенность спектра липопротеинов, у жителей Российской Федерации (по данным исследования ЭССЕ-РФ). Профилактическая медицина. 2016;19(1):15–23. DOI: 10.17116/profmed201619115-23.

6. Zheutlin A.R., Harris B.R.E., Stulberg E.L. Hyperlipidemia-Attributed Deaths in the U.S. in 2018-2021. Am. J. Prev. Med. 2024;66(6):1075–1077. DOI: 10.1016/j.amepre.2024.02.014.

7. Halcox J.P., Banegas J.R., Roy C., Dallongeville J., De Backer G., Guallar E. et al. Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study. BMC Cardiovasc. Disord. 2017;17(1):160. DOI: 10.1186/s12872-017-0591-5.

8. Khanali J., Ghasemi E., Rashidi M.M., Ahmadi N., Ghamari S.H., Azangou-Khyavy M. et al. Prevalence of plasma lipid abnormalities and associated risk factors among Iranian adults based on the findings from STEPs survey 2021. Sci. Rep. 2023;13(1):15499. DOI: 10.1038/s41598-023-42341-5.

9. Lu Y., Zhang H., Lu J., Ding Q., Li X., Wang X. et al. China patient-centered evaluative assessment of cardiac events million persons project collaborative group. Prevalence of dyslipidemia and availability of lipid-lowering medications among primary health care settings in China. JAMA Netw. Open. 2021;4(9):e2127573. DOI: 10.1001/jamanetworkopen.2021.27573.

10. Majee S., Banerjee A. Suppression of inflammatory macrophages reduces atherosclerosis. J. Physiol. 2024;602(16):3867–3869. DOI: 10.1113/JP287013.

11. Ali I., Zhang H., Zaidi S.A.A., Zhou G. Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications. Ageing Res. Rev. 2024;96:102273. DOI: 10.1016/j.arr.2024.102273.

12. Aldana-Bitar J., Golub I.S., Moore J., Krishnan S., Verghese D., Manubolu V.S. et al. Colchicine and plaque: A focus on atherosclerosis imaging. Prog. Cardiovasc. Dis. 2024;84:68–75. DOI: 10.1016/j.pcad.2024.02.010.

13. Avagimyan A., Fogacci F., Pogosova N., Kakturskiy L., Jndoyan Z., Faggiano A. et al. Methotrexate & rheumatoid arthritis associated atherosclerosis: A narrative review of multidisciplinary approach for risk modification by the international board of experts. Curr. Probl. Cardiol. 2024;49(2):102230. DOI: 10.1016/j.cpcardiol.2023.102230.

14. Abdelmaseih R., Alsamman M.M., Faluk M., Hasan S.M. Cardiovascular Outcomes With Anti-Inflammatory Therapies: Review of Literature. Curr. Probl. Cardiol. 2022;47(6):100840. DOI: 10.1016/j.cpcardiol.2021.100840.

15. Poznyak A.V., Bharadwaj D., Prasad G., Grechko A.V., Sazonova M.A., Orekhov A.N. Anti-inflammatory therapy for atherosclerosis: focusing on cytokines. Int. J. Mol. Sci. 2021;22(13):7061. DOI: 10.3390/ijms22137061.

16. Ridker P.M. The time to initiate anti-inflammatory therapy for patients with chronic coronary atherosclerosis has arrived. Circulation. 2023;148(14):1071–1073. DOI: 10.1161/CIRCULATIONAHA.123.066510.

17. Theofilis P., Oikonomou E., Chasikidis C., Tsioufis K., Tousoulis D. Inflammasomes in atherosclerosis-from pathophysiology to treatment. Pharmaceuticals (Basel). 2023;16(9):1211. DOI: 10.3390/ph16091211.

18. Ionov A.Yu., Kuznetsova E.A., Kindalyova O.G., Kryuchkova I.V., Poplavskaya E.E., Avagimyan A.A. Clinical significance of endocrine disorders in the development of early vascular aging in males with abdominal obesity and concomitant arterial hypertension: An observational cohort study. Kuban Scientific Medical Bulletin. 2024;31(1):74–87. DOI: 10.25207/1608-6228-2024-31-1-74-87.

19. L’homme L., Esser N., Riva L., Scheen A., Paquot N., Piette J. et al. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages. J. Lipid. Res. 2013;54(11):2998–3008. DOI: 10.1194/jlr.M037861.

20. Bleda S., de Haro J., Varela C., Ferruelo A., Acin F. Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells. International Journal of Cardiology. 2016;220:52–55. DOI: 10.1016/j.ijcard.2016.06.193.

21. Folco E.J., Sukhova G.K., Quillard T., Libby P. Moderate hypoxia potentiates interleukin-1β production in activated human macrophages. Circ. Res. 2014;115(10):875–883. DOI: 10.1161/CIRCRESAHA.115.304437.

22. Xiao H., Lu M., Lin T.Y., Chen Z., Chen G., Wang W.C. et al. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation. 2013;128(6):632–642. DOI: 10.1161/CIRCULATIONAHA.113.002714.

23. Lin L., Zhang M.X., Zhang L., Zhang D., Li C., Li Y.L. Autophagy, pyroptosis, and ferroptosis: new regulatory mechanisms for atherosclerosis. Front. Cell Dev. Biol. 2022;9:809955. DOI: 10.3389/fcell.2021.809955.

24. Silvis M.J.M., Demkes E.J., Fiolet A.T.L., Dekker M., Bosch L., van Hout G.P.J. et al. Immunomodulation of the NLRP3 inflammasome in atherosclerosis, coronary artery disease, and acute myocardial infarction. J. Cardiovasc. Transl. Res. 2021;14(1):23–34. DOI: 10.1007/s12265-020-10049-w.

25. Martínez G.J., Celermajer D.S., Patel S. The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation. Atherosclerosis. 2018;269:262–271. DOI: 10.1016/j.atherosclerosis.2017.12.027.

26. Wang X., Shen Y., Shang M., Liu X., Munn L.L. Endothelial mechanobiology in atherosclerosis. Cardiovasc. Res. 2023;119(8):1656–1675. DOI: 10.1093/cvr/cvad076.

27. Qaisar S., Brodsky L.D., Barth R.F., Leier C., Buja L.M., Yildiz V. et al. An unexpected paradox: wall shear stress in the aorta is less in patients with severe atherosclerosis regardless of obesity. Cardiovasc. Pathol. 2021;51:107313. DOI: 10.1016/j.carpath.2020.107313.

28. Roux E., Bougaran P., Dufourcq P., Couffinhal T. Fluid shear stress sensing by the endothelial layer. Front. Physiol. 2020;11:861. DOI: 10.3389/fphys.2020.00861.

29. Sergin I., Evans T.D., Bhattacharya S., Razani B. Hypoxia in plaque macrophages: a new danger signal for interleukin-1β activation? Circ. Res. 2014;115(10):817–820. DOI: 10.1161/CIRCRESAHA.114.305197.

30. Zhou Z., Korteland S., Tardajos-Ayllon B., Wu J., Chambers E., Weninck J. et al. Shear stress is uncoupled from atheroprotective KLK10 in atherosclerotic plaques. Atherosclerosis. 2024;398:118622. DOI: 10.1016/j.atherosclerosis.2024.118622.

31. Shirai K., Hitsumoto T., Sato S., Takahashi M., Saiki A., Nagayama D. et al. The Process of Plaque Rupture: The role of vasa vasorum and medial smooth muscle contraction monitored by the cardio-ankle vascular index. J. Clin. Med. 2023;12(23):7436. DOI: 10.3390/jcm12237436.

32. Tinajero M.G., Gotlieb A.I. Recent developments in vascular adventitial pathobiology: the dynamic adventitia as a complex regulator of vascular disease. Am. J. Pathol. 2020;190(3):520–534. DOI: 10.1016/j.ajpath.2019.10.021.

33. Elmarasi M., Elmakaty I., Elsayed B., Elsayed A., Zein J., Boudaka A., Eid A. Phenotypic switching of vascular smooth muscle cells in atherosclerosis, hypertension, and aortic dissection. J. Cell Physiol. 2024;239(4):e31200. DOI: 10.1002/jcp.31200.

34. Mohanta S.K., Peng L., Li Y., Lu S., Sun T., Carnevale L. et al. Neuroimmune cardiovascular interfaces control atherosclerosis. Nature. 2022;605(7908):152–159. DOI: 10.1038/s41586-022-04673-6.

35. Sluiter T.J., Buul J.D., Huveneers S., Quax P.H., de Vries M.R. Endothelial barrier function and leukocyte transmigration in atherosclerosis. Biomedicines. 2021;9(4):328. DOI: 10.3390/biomedicines9040328.

36. Juettner V.V., Kruse K., Dan A., Vu V.H., Khan Y., Le J. et al. VE-PTP stabilizes VE-cadherin junctions and the endothelial barrier via a phosphatase-independent mechanism. J. Cell Biol. 2019;218(5):1725–1742. DOI: 10.1083/jcb.201807210.

37. Nawroth R., Poell G., Ranft A., Kloep S., Samulowitz U., Fachinger G. et al. VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts. EMBO J. 2002;21(18):4885–4895. DOI: 10.1093/emboj/cdf497.

38. Broermann A., Winderlich M., Block H., Frye M., Rossaint J., Zarbock A. et al. Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. J. Exp. Med. 2011;208(12):2393–2401. DOI: 10.1084/jem.20110525.

39. Zhang S., Zhang Q., Lu Y., Chen J., Liu J., Li Z. et al. Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications. Int. J. Mol. Sci. 2024;25(7):4096. DOI: 10.3390/ijms25074096.

40. Bonowicz K., Mikołajczyk K., Faisal I., Qamar M., Steinbrink K., Kleszczyński K. et al. Mechanism of extracellular vesicle secretion associated with TGF-β-dependent inflammatory response in the tumor microenvironment. Int. J. Mol. Sci. 2022;23(23):15335. DOI: 10.3390/ijms232315335.

41. Lin Y.C., Sahoo B.K., Gau S.S., Yang R.B. The biology of SCUBE. J. Biomed Sci. 2023;30(1):33. DOI: 10.1186/s12929-023-00925-3.

42. Lin Y.C., Chang Y.J., Gau S.S., Lo C.M., Yang R.B. et al. SCUBE2 regulates adherens junction dynamics and vascular barrier function during inflammation. Cardiovasc. Res. 2024; 120(13):1636–1649. DOI: 10.1093/cvr/cvae132.

43. Benz K., Varga I., Neureiter D., Campean V., Daniel C., Heim C. et al. Vascular inflammation and media calcification are already present in early stages of chronic kidney disease. Cardiovasc. Pathol. 2017;27:57–67. DOI: 10.1016/j.carpath.2017.01.004.

44. Jansen I., Cahalane R., Hengst R., Akyildiz A., Farrell E., Gijsen F. et al. The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics. Basic Res. Cardiol. 2024;119(2):193–213. DOI: 10.1007/s00395-024-01033-5.

45. Akers E.J., Nicholls S.J., Di Bartolo B.A. Plaque calcification: do lipoproteins have a role? Arterioscler. Thromb. Vasc. Biol. 2019;39(10):1902–1910. DOI: 10.1161/ATVBAHA.119.311574.

46. Shioi A., Ikari Y. Plaque calcification during atherosclerosis progression and regression. J. Atheroscler. Thromb. 2018;25(4):294–303. DOI: 10.5551/jat.RV17020.

47. Woo S.H., Kim D.Y., Choi J.H. Roles of vascular smooth muscle cells in atherosclerotic calcification. J. Lipid. Atheroscler. 2023;12(2):106–118. DOI: 10.12997/jla.2023.12.2.106.

48. Zhang F., Guo X., Xia Y., Mao L. An update on the phenotypic switching of vascular smooth muscle cells in the pathogenesis of atherosclerosis. Cell Mol. Life Sci. 2021;79(1):6. DOI: 10.1007/s00018-021-04079-z.

49. Speer M.Y., Li X., Hiremath P.G., Giachelli C.M. Runx2/Cbfa1, but not loss of myocard in, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis. J. Cell Biochem. 2010;110(4):935–947. DOI: 10.1002/jcb.22607.

50. Segura A.M., Radovancevic R., Connelly J.H., Loyalka P., Gregoric I.D., Buja L.M. et al. Endomyocardial nodular calcification as a cause of heart failure. Cardiovasc. Pathol. 2011;20(5):e185–e188. DOI: 10.1016/j.carpath.2010.08.003.

51. Zazzeroni L., Faggioli G., Pasquinelli G. Mechanisms of arterial calcification: the role of matrix vesicles. Eur. J. Vasc. Endovasc. Surg. 2018;55(3):425–432. DOI: 10.1016/j.ejvs.2017.12.009.

52. Полонская Я.В., Каштанова Е.В., Стахнёва Е.М., Ледовских С.Р., Гарбузова Е.В., Шрамко В.С. и др. Уровни металлопротеиназ и гормонов жировой ткани у мужчин с коронарным атеросклерозом. Бюллетень сибирской медицины. 2023;22(4):73–78. DOI: 10.20538/1682-0363-2023-4-73-78.

53. Полонская Я.В., Рагино Ю.И. Металлопротеиназы и атеросклероз. Атеросклероз. 2017;13(3):50–55.

54. Волков А.М., Мурашов И.С., Полонская Я.В., Савченко С.В., Казанская Г.М., Кливер Е.Э., Чернявский А.М. Изменение содержания матриксных металлопротеиназ и их тканевая экспрессия в атеросклеротических бляшках разных типов. Кардиология. 2018;58(10):12–18. DOI: 10.18087/cardio.2018.10.10180.

55. Полонская Я.В., Каштанова Е.В., Стахнева Е.М., Садовский Е.В., Рагино Ю.И. Роль металлопротеиназ и тканевых ингибиторов металлопротеиназ в развитии коронарного атеросклероза. Атеросклероз. 2021;17(3):76–78. DOI: 10.52727/2078-256X-2021-17-3-76-78.

56. Olejarz W., Łacheta D., Kubiak-Tomaszewska G. Matrix metalloproteinases as biomarkers of atherosclerotic plaque instability. Int. J. Mol. Sci. 2020;21(11):3946. DOI: 10.3390/ijms21113946.

57. Samah N., Ugusman A., Hamid A.A., Sulaiman N., Aminuddin A. Role of matrix metalloproteinase-2 in the development of atherosclerosis among patients with coronary artery disease. Mediators Inflamm. 2023;2023:9715114. DOI: 10.1155/2023/9715114.

58. Yang C., Qiao S., Song Y., Liu Y., Tang Y., Deng L. et al. Procollagen type I carboxy-terminal propeptide (PICP) and MMP-2 are potential biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Cardiovasc. Pathol. 2019;43:107150. DOI: 10.1016/j.carpath.2019.107150.

59. Bräuninger H., Krüger S., Bacmeister L., Nyström A., Eyerich K., Westermann D. et al. Matrix metalloproteinases in coronary artery disease and myocardial infarction. Basic Res. Cardiol. 2023;118(1):18. DOI: 10.1007/s00395-023-00987-2.

60. Shakhtshneider E.V., Ivanoshchuk D.E., Ragino Yu.I., Fishman V.S., Polonskaya Ya.V., Kashtanova E.V. et al. Analysis of differential expression of lipid metabolism genes in atherosclerotic plaques in patients with coronary atherosclerosis. Siberian Journal of Clinical and Experimental Medicine. 2021;36(4):156–163. DOI: 10.29001/2073-8552-2021-36-4-156-163.

61. Garbuzova E.V., Polonskaya Ya.V., Kashtanova E.V., Stakhneva E.M., Shramko V.S., Murashov I.S. et al. Biomolecules of adipose tissue in atherosclerotic plaques of men with coronary atherosclerosis. Kardiologiia. 2024;64(8):39–47. DOI: 10.18087/cardio.2024.8.n2634.

62. Luo X., Lv Y., Bai X., Qi J., Weng X., Liu S. et al. Plaque erosion: A distinctive pathological mechanism of acute coronary syndrome. Front. Cardiovasc. Med. 2021;8:711453. DOI: 10.3389/fcvm.2021.711453.

63. Fahed A.C., Jang I.K. Plaque erosion and acute coronary syndromes: phenotype, molecular characteristics and future directions. Nat. Rev. Cardiol. 2021;18:724–734. DOI: 10.1038/s41569-021-00542-3.

64. Lv Y., Pang X., Cao Z., Song C., Liu B., Wu W. et al. Evolution and function of the notch signaling pathway: an invertebrate perspective. Int. J. Mol. Sci. 2024;25(6):3322. DOI: 10.3390/ijms25063322.

65. Rizzo P., Ferrari R. The Notch pathway: a new therapeutic target in atherosclerosis? Eur. Heart J. Suppl. 2015;17 (Suppl._A):A74–A76. DOI: 10.1093/eurheartj/suv011.

66. Suarez Rodriguez F., Sanlidag S., Sahlgren C. Mechanical regulation of the notch signaling pathway. Curr. Opin. Cell Biol. 2023;85:102244. DOI: 10.1016/j.ceb.2023.102244.

67. Vieceli Dalla Sega F., Fortini F., Aquila G., Campo G., Vaccarezza M., Rizzo P. Notch signaling regulates immune responses in atherosclerosis. Front. Immunol. 2019;10:1130. DOI: 10.3389/fimmu.2019.01130.

68. Souilhol C., Tardajos Ayllon B., Li X. JAG1-NOTCH4 mechanosensing drives atherosclerosis. Sci. Adv. 2022;8(35):eabo7958. DOI: 10.1126/sciadv.abo7958.

69. Harrison O.J., Visan A.C., Moorjani N. Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions. Trends Cardiovasc. Med. 2019;29(2):61–68. DOI: 10.1016/j.tcm.2018.06.008.

70. Mao C., Ma Z., Jia Y., Li W., Xie N., Zhao G. et al. Nidogen-2 maintains the contractile phenotype of vascular smooth muscle cells and prevents neointima formation via bridging jagged1-notch3 signaling. Circulation. 2021;144(15):1244–1261. DOI: 10.1161/CIRCULATIONAHA.120.053361.

71. Kocełak P., Puzianowska-Kuźnicka M., Olszanecka-Glinianowicz M., Chudek J. Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification. Adv. Clin. Exp. Med. 2024;33(5):519–532. DOI: 10.17219/acem/169567.

72. Abou Azar F., Lim G.E. Metabolic contributions of wnt signaling: more than controlling flight. Front. Cell Dev. Biol. 2021;9:709823. DOI: 10.3389/fcell.2021.709823.

73. Wang K., Zhang R., Lehwald N., Tao G.Z., Liu B., Liu B. et al. Wnt/β-catenin signaling activation promotes lipogenesis in the steatotic liver via physical mTOR interaction. Front. Endocrinol. (Lausanne). 2023;14:1289004. DOI: 10.3389/fendo.2023.1289004.

74. Weinstock A., Rahman K., Yaacov O., Nishi H., Menon P., Nikain C.A. et al. Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis. Elife. 2021;10:e67932. DOI: 10.7554/eLife.67932.

75. Zhang Y., Wu H., He R., Ye C., Chen H., Wang J. et al. Dickkopf-2 knockdown protects against classic macrophage polarization and lipid loading by activation of Wnt/β-catenin signaling. J. Cardiol. 2021;78(4):328–333. DOI: 10.1016/j.jjcc.2021.04.010.

76. Hassanabad A.F., Zarzycki A.N., Patel V.B., Fedak P.W.M. Current concepts in the epigenetic regulation of cardiac fibrosis. Cardiovasc. Pathol. DOI: 10.1016/j.carpath.2024.107673.

77. Wang J., Hu X., Hu X., Gao F., Li M., Cui Y. et al. MicroRNA-520c-3p targeting of RelA/p65 suppresses atherosclerotic plaque formation. Int. J. Biochem. Cell Biol. 2021;131:105873. DOI: 10.1016/j.biocel.2020.105873.

78. Li Z., Xu C., Sun D. MicroRNA-488 serves as a diagnostic marker for atherosclerosis and regulates the biological behavior of vascular smooth muscle cells. Bioengineered. 2021;12(1):4092–4099. DOI: 10.1080/21655979.2021.1953212.

79. Lv D., Guo Y., Zhang L., Li X., Li G. Circulating miR-183-5p levels are positively associated with the presence and severity of coronary artery disease. Front. Cardiovasc. Med. 2023;10:1196348. DOI: 10.3389/fcvm.2023.1196348.

80. Kim M., Zhang X. The profiling and role of miRNAs in diabetes mellitus. J. Diabetes Clin. Res. 2019;1(1):5–23. DOI: 10.33696/diabetes.1.003.

81. Jiang Q., Li Y., Wu Q., Huang L., Xu J., Zeng Q. Pathogenic role of microRNAs in atherosclerotic ischemic stroke: implications for diagnosis and therapy. Genes Dis. 2021;9(3):682–696. DOI: 10.1016/j.gendis.2021.01.001.

82. Mahjoubin-Tehran M., Aghaee-Bakhtiari S.H., Sahebkar A., Butler A.E., Oskuee R.K. In silico and in vitro analysis of microRNAs with therapeutic potential in atherosclerosis. Sci. Rep. 2022;12(1):20334. DOI: 10.1038/s41598-022-24260-z.

83. Peng Q., Yin R., Zhu X., Jin L., Wang J., Pan X. et al. miR- 155 activates the NLRP3 inflammasome by regulating the MEK/ERK/NF-κB pathway in carotid atherosclerotic plaques in ApoE-/- mice. J. Physiol. Biochem. 2022;78(2):365–375. DOI: 10.1007/s13105-022-00871-y.

84. Vavlukis M., Vavlukis A. Adding ezetimibe to statin therapy: latest evidence and clinical implications. Drugs Context. 2018;7:212534. DOI: 10.7573/dic.212534.

85. Tricarico P.M., Crovella S., Celsi F. Mevalonate pathway blockade, mitochondrial dysfunction and autophagy: a possible link. Int. J. Mol. Sci. 2015;16(7):16067–16084. DOI: 10.3390/ijms160716067.

86. Kim S.W., Kang H.J., Jhon M., Kim J.W., Lee J.Y., Walker A.J. et al. Statins and inflammation: new therapeutic opportunities in psychiatry. Front. Psychiatry. 2019;10:103. DOI: 10.3389/fpsyt.2019.00103.

87. Koushki K., Shahbaz S.K., Mashayekhi K., Sadeghi M., Zayeri Z.D., Taba M.Y. et al. Anti-inflammatory action of statins in cardiovascular disease: the role of inflammasome and toll-like receptor pathways. Clin. Rev. Allergy Immunol. 2021;60(2):175–199. DOI: 10.1007/s12016-020-08791-9.

88. Zivkovic S., Maric G., Cvetinovic N., Lepojevic-Stefanovic D., Bozic Cvijan B. Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review. Nutrients. 2023;15(6):1517. DOI: 10.3390/nu15061517.

89. Frostegård J., Zhang Y., Sun J., Yan K., Liu A. Oxidized low-density lipoprotein (OxLDL)-treated dendritic cells promote activation of t cells in human atherosclerotic plaque and blood, which is repressed by statins: microRNA let-7c is integral to the effect. J. Am. Heart Assoc. 2016;5(9):e003976. DOI: 10.1161/JAHA.116.003976.

90. Fogacci F., Giovannini M., Tocci G., Imbalzano E., Borghi C., Cicero A.F.G. Effect of Coenzyme Q10 on Physical Performance in Older Adults with Statin-Associated Asthenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J. Clin. Med. 2024;13(13):3741. DOI: 10.3390/jcm13133741.

91. Кобалава Ж.Д., Лазарев П.В., Виллевальде С.В. Сахарный диабет, ассоциированный с терапией статинами: статус проблемы 2018 год. Российский кардиологический журнал. 2018;(9):89–99. DOI: 10.15829/1560-4071-2018-9-89-99.

92. Cicero A.F.G., Morbini M., Bove M., D’Addato S., Fogacci F., Rosticci M. et al. Additional therapy for cholesterol lowering in ezetimibe-treated, statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic. Curr. Med. Res. Opin. 2016;32(10):1633–1638. DOI: 10.1080/03007995.2016.1190326.

93. Strilchuk L., Tocci G., Fogacci F., Cicero A.F.G. An overview of rosuvastatin/ezetimibe association for the treatment of hypercholesterolemia and mixed dyslipidemia. Expert Opin. Pharmacother. 2020;21(5):531–539. DOI: 10.1080/14656566.2020.1714028.

94. Fogacci F., Borghi C., Cicero A.F.G. Misinterpreting data in lipidology in the era of COVID-19. J. Clin. Lipidol. 2020;14(4):543–544. DOI: 10.1016/j.jacl.2020.07.004.

95. Mohseni M., Mohammadifard N., Hassannejad R., Aghabozorgi M., Shirani F., Sadeghi M. et al. Longitudinal association of dietary habits and the risk of cardiovascular disease among Iranian population between 2001 and 2013: the Isfahan Cohort Study. Sci. Rep. 2023;13(1):5364. DOI: 10.1038/s41598-023-32387-w.

96. Pauley M.E., Vinovskis C., MacDonald A., Baca M., Pyle L., Wadwa R.P. et al. Triglyceride content of lipoprotein subclasses and kidney hemodynamic function and injury in adolescents with type 1 diabetes. J. Diabetes Complications. 2023;37(2):108384. DOI: 10.1016/j.jdiacomp.2022.108384.

97. Liu H.H., Li S., Cao Y.X., Guo Y.L., Zhu C.G., Wu N.Q. et al. Association of triglyceride-rich lipoprotein-cholesterol with recurrent cardiovascular events in statin-treated patients according to different inflammatory status. Atherosclerosis. 2021;330:29–35. DOI: 10.1016/j.atherosclerosis.2021.06.907.

98. Fogacci F., Yerlitaş S.İ., Giovannini M., Zararsız G., Lido P., Borghi C. et al. Sex X time interactions in Lp(a) and LDL-C response to evolocumab. Biomedicines. 2023;11(12):3271. DOI: 10.3390/biomedicines11123271.

99. Cicero A.F.G., Toth P.P., Fogacci F., Virdis A., Borghi C. Improvement in arterial stiffness after short-term treatment with PCSK9 inhibitors. Nutr. Metab. Cardiovasc. Dis. 2019;29(5):527–529. DOI: 10.1016/j.numecd.2019.01.010.

100. Cicero A.F.G., Fogacci F., Bragagni A., Borghi C. Shortterm evolocumab-induced tendon xanthomas regression in an elderly patient with homozygous familial hypercholesterolemia. Intern. Emerg Med. 2023;18(1):307–310. DOI: 10.1007/s11739-022-03106-6.

101. Sabatine M.S., Giugliano R.P., Keech A.C., Honarpour N., Wiviott S.D., Murphy S.A. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 2017;376(18):1713–1722. DOI: 10.1056/NEJMoa1615664.

102. Schwartz G.G., Steg P.G., Szarek M., Bhatt D.L., Bittner V.A., Diaz R. et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N. Engl. J. Med. 2018;379(22):2097–2107. DOI: 10.1056/NEJMoa1801174.

103. Bodapati A.P., Hanif A., Okafor D.K., Katyal G., Kaur G., Ashraf H. et al. PCSK-9 Inhibitors and Cardiovascular Outcomes: A Systematic Review With Meta-Analysis. Cureus. 2023;15(10):e46605. DOI: 10.7759/cureus.46605.

104. Khan S.U., Talluri S., Riaz H., Rahman H., Nasir F., Bin Riaz I. et al. A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes. Eur. J. Prev. Cardiol. 2018;25(8):844–853. DOI: 10.1177/2047487318766612.

105. Намитоков А.М., Зафираки В.К., Карабахциева К.В. Перспективы применения PCSK-9-модифицирующих агентов при остром коронарном синдроме. Инновационная медицина Кубани. 2024;(2):124–128. DOI: 10.35401/2541-9897-2024-9-2-124-128.

106. Cheng J.M., Oemrawsingh R.M., Garcia-Garcia H.M. PCSK9 in relation to coronary plaque inflammation: Results of the ATHEROREMO-IVUS study. Atherosclerosis. 2016;248:117–122. DOI: 10.1016/j.atherosclerosis.2016.03.010.

107. Almontashiri N.A., Vilmundarson R.O., Ghasemzadeh N., Dandona S., Roberts R., Quyyumi A.A. et al. Plasma PCSK9 levels are elevated with acute myocardial infarction in two independent retrospective angiographic studies. PLoS One. 2014;9(9):e106294. DOI: 10.1371/journal.pone.0106294.

108. Badimon L., Luquero A., Crespo J., Peña E., Borrell-Pages M. PCSK9 and LRP5 in macrophage lipid internalization and inflammation. Cardiovasc. Res. 2021;117(9):2054–2068. DOI: 10.1093/cvr/cvaa254.

109. Wu N.Q., Shi H.W., Li J.J. Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review. Front. Cardiovasc. Med. 2022;9:763516. DOI: 10.3389/fcvm.2022.763516.

110. Fruchart Gaillard C., Ouadda A.B.D., Ciccone L., Girard E., Mikaeeli S., Evagelidis A. et al. Molecular interactions of PCSK9 with an inhibitory nanobody, CAP1 and HLA-C: functional regulation of LDLR levels. Mol. Metab. 2023;67:101662. DOI: 10.1016/j.molmet.2022.101662.

111. Shin D., Kim S., Lee H., Lee J., Park H.W. PCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor. Nat. Commun. 2024;15(1):2789. DOI: 10.1038/s41467-024-46336-2.

112. Banerjee Y., Pantea Stoian A., Cicero A.F.G., Fogacci F., Nikolic D., Sachinidis A. et al. Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia. Expert Opin. Drug Saf. 2022;21(1):9–20. DOI: 10.1080/14740338.2022.1988568.

113. Cicero A.F.G., Fogacci F., Zambon A., Toth P.P., Borghi C. Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies. Am. Heart J. Plus. 2022;13:100127. DOI: 10.1016/j.ahjo.2022.100127.

114. Strilchuk L., Fogacci F., Cicero A.F. Safety and tolerability of injectable lipid-lowering drugs: an update of clinical data. Expert Opin. Drug Saf. 2019;18(7):611–621. DOI: 10.1080/14740338.2019.1620730.

115. Воевода М.И., Гуревич В.С., Ежов М.В., Сергиенко И.В. Инклисиран – новая эра в гиполипидемической терапии. Кардиология. 2022;62(6):57–62. DOI: 10.18087/cardio.2022.6.n2115.

116. Khan S.A., Naz A., Qamar Masood M., Shah R. Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia. Am. J. Cardiol. 2020;134:69–73. DOI: 10.1016/j.amjcard.2020.08.018.

117. Fogacci F., Di Micoli V., Sabouret P., Giovannini M., Cicero A.F.G. Lifestyle and lipoprotein(a) levels: does a specific counseling make sense? J. Clin. Med. 2024;13(3):751. DOI: 10.3390/jcm13030751.

118. Fogacci F., Di Micoli V., Avagimyan A., Giovannini M., Imbalzano E., Cicero A.F.G. Assessment of apolipoprotein(a) isoform size using phenotypic and genotypic methods. Int. J. Mol. Sci. 2023;24(18):13886. DOI: 10.3390/ijms241813886.

119. Dzobo K.E., Kraaijenhof J.M., Stroes E.S.G., Nurmohamed N.S., Kroon J. Lipoprotein(a): an underestimated inflammatory mastermind. Atherosclerosis. 2022;349:101–109. DOI: 10.1016/j.atherosclerosis.2022.04.004.

120. Gianos E., Duell P.B., Toth P.P., Moriarty P.M., Thompson G.R., Brinton E.A. et al. American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; and Council on Peripheral Vascular Disease. Lipoprotein Apheresis: Utility, Outcomes, and Implementation in Clinical Practice: A Scientific Statement From the American Heart Association. Arterioscler. Thromb. Vasc. Biol. 2024. DOI: 10.1161/ATV.0000000000000177.

121. Di Fusco S.A., Maggioni A.P., Scicchitano P., Zuin M., D’Elia E., Colivicchi F. Lipoprotein (a), inflammation, and atherosclerosis. J. Clin. Med. 2023;12(7):2529. DOI: 10.3390/jcm12072529.

122. Lampsas S., Xenou M., Oikonomou E., Pantelidis P., Lysandrou A., Sarantos S. et al. Lipoprotein(a) in atherosclerotic diseases: from pathophysiology to diagnosis and treatment. Molecules. 2023;28(3):969. DOI: 10.3390/molecules28030969.

123. Afzal Z., Cao H., Chaudhary M., Chigurupati H.D., Neppala S., Alruwaili W. et al. Elevated lipoprotein(a) levels: A crucial determinant of cardiovascular disease risk and target for emerging therapies. Curr. Probl. Cardiol. 2024;49(8):102586. DOI: 10.1016/j.cpcardiol.2024.102586.

124. Schnitzler J.G., Hoogeveen R.M., Ali L., Prange K.H.M., Waissi F., van Weeghel M. et al. Atherogenic lipoprotein(a) increases vascular glycolysis, thereby facilitating inflammation and leukocyte extravasation. Circ. Res. 2020;126(10):1346–1359. DOI: 10.1161/CIRCRESAHA.119.316206.

125. Karwatowska-Prokopczuk E., Lesogor A., Yan J.H., Hurh E., Hoenlinger A., Margolskee A. et al. Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects. J. Clin. Lipidol. 2023;17(1):181–188. DOI: 10.1016/j.jacl.2022.12.001.

126. O’Donoghue M.L., Rosenson R.S., Gencer B., López J.A.G., Lepor N.E., Baum S.J. et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N. Engl. J. Med. 2022;387(20):1855–1864. DOI: 10.1056/NEJMoa2211023.

127. Nissen S.E., Wolski K., Watts G.F., Koren M.J., Fok H., Nicholls S.J., Rider D.A. et al. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024;331(18):1534–1543. DOI: 10.1001/jama.2024.4504.

128. Nissen S.E., Linnebjerg H., Shen X., Wolski K., Ma X., Lim S. et al. Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial. JAMA. 2023;330(21):2075–2083. DOI: 10.1001/jama.2023.21835.

129. Nicholls S.J., Nissen S.E., Fleming C., Urva S., Suico J., Berg P.H. et al. Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial. JAMA. 2023;330(11):1042–1053. DOI: 10.1001/jama.2023.16503.

130. O’Donoghue M.L., Rosenson R.S., López J.A.G., Lepor N.E., Baum S.J., Stout E. et al. The off-treatment effects of olpasiran on lipoprotein(a) lowering: OCEAN(a)-dose extension period results. J. Am. Coll. Cardiol. 2024;84(9):790–797. DOI: 10.1016/j.jacc.2024.05.058.

131. Nicholls S.J., Ni W., Rhodes G.M., Nissen S.E., Navar A.M., Michael L.F. et al. Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial. JAMA. 2024:e2424017. DOI: 10.1001/jama.2024.24017.

132. Nissen S.E., Wang Q., Nicholls S.J., Navar A.M., Ray K.K., Schwartz G.G. et al. Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. JAMA. 2024:e2421957. DOI: 10.1001/jama.2024.21957.

133. Kolovou G., Kolovou V., Katsiki N. Volanesorsen: A new era in the treatment of severe hypertriglyceridemia. J. Clin. Med. 2022;11(4):982. DOI: 10.3390/jcm11040982.

134. Stroes E.S.G., Alexander V.J., Karwatowska-Prokopczuk E. Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome. N. Engl. J. Med. 2024;390(19):1781–1792. DOI: 10.1056/NEJMoa2400201.

135. Witztum J.L., Gaudet D., Freedman S.D., Alexander V.J., Digenio A., Williams K.R. et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N. Engl. J. Med. 2019;381(6):531–542. DOI: 10.1056/NEJMoa1715944.

136. Witztum J.L., Gaudet D., Arca M., Jones A., Soran H., Gouni-Berthold I. et al. Corrigendum to Volanesorsen and triglyceride levels in familial chylomicronemia syndrome: Long-term efficacy and safety data from patients in an open-label extension trial. J. Clin. Lipidol. 2024;18(3):e482–e483. DOI: 10.1016/j.jacl.2023.09.010.

137. Gouni-Berthold I., Alexander V.J., Yang Q., Hurh E., Steinhagen-Thiessen E., Moriarty P.M. et al. Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021;9(5):264–275. DOI: 10.1016/S2213-8587(21)00046-2.

138. Hegele R.A. Apolipoprotein C-III inhibition to lower triglycerides: one ring to rule them all? Eur. Heart J. 2022;43(14):1413–1415. DOI: 10.1093/eurheartj/ehab890.

139. Tardif J.C., Karwatowska-Prokopczuk E., Amour E.S., Ballantyne C.M., Shapiro M.D., Moriarty P.M. et al. Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur. Heart J. 2022;43(14):1401–1412. DOI: 10.1093/eurheartj/ehab820.

140. Петросян А.С., Рудь Р.С., Поляков П.П., Каде А.Х., Занин С.А. Патогенетические основы эффектов бемпедоевой кислоты. Рациональная фармакотерапия в кардиологии. 2022;18(6):734–741. DOI: 10.20996/1819-6446-2022-12-11.

141. Ruscica M., Sirtori C.R., Carugo S., Banach M., Corsini A. Bempedoic acid: for whom and when. Curr. Atheroscler. Rep. 2022;24(10):791–801. DOI: 10.1007/s11883-022-01054-2.

142. Мазеркина И.А., Букатина Т.М., Александрова Т.В. Эффективность бемпедоевой кислоты как гиполипидемического средства. Безопасность и риск фармакотерапии. 2023;11(3):292–302. DOI: 10.30895/2312-7821-2023-11-3-292-302.

143. Ballantyne C.M., Banach M., Mancini G.B.J., Lepor N.E., Hanselman J.C., Zhao X. et al. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis. 2018;277:195–203. DOI: 10.1016/j.atherosclerosis.2018.06.002.

144. Ray K.K., Bays H.E., Catapano A.L., Lalwani N.D., Bloedon L.T., Sterling L.R. et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N. Engl. J. Med. 2019;380(11):1022–1032. DOI: 10.1056/NEJMoa1803917.

145. Goldberg A.C., Leiter L.A., Stroes E.S.G., Baum S.J., Hanselman J.C., Bloedon L.T. et al. Effect of Bempedoic Acid vs Placebo Added to Maximally Tolerated Statins on Low-Density Lipoprotein Cholesterol in Patients at High Risk for Cardiovascular Disease: The CLEAR Wisdom Randomized Clinical Trial. JAMA. 2019;322(18):1780–1788. DOI: 10.1001/jama.2019.16585.

146. Laufs U., Banach M., Mancini G.B.J., Gaudet D., Bloedon L.T., Sterling L.R. et al. Efficacy and safety of bempedoic acid in patients with hypercholesterolemia and statin intolerance. J. Am. Heart Assoc. 2019;8(7):e011662. DOI: 10.1161/JAHA.118.011662.

147. Pinkosky S.L., Filippov S., Srivastava R.A., Hanselman J.C., Bradshaw C.D., Hurley T.R. et al. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J. Lipid Res. 2013;54(1):134–151. DOI: 10.1194/jlr.M030528.

148. Pinkosky S.L., Newton R.S., Day E.A., Ford R.J., Lhotak S., Austin R.C., Birch C.M. et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat. Commun. 2016;7:13457. DOI: 10.1038/ncomms13457.

149. Morrow M.R., Batchuluun B., Wu J., Ahmadi E., Leroux J.M., Mohammadi-Shemirani P. et al. Inhibition of ATP-citrate lyase improves NASH, liver fibrosis, and dyslipidemia. Cell Metab. 2022;34(6):919–936.e8. DOI: 10.1016/j.cmet.2022.05.004.

150. Raal F.J., Rosenson R.S., Reeskamp L.F., Hovingh G.K., Kastelein J.J.P., Rubba P. et al. Evinacumab for homozygous familial hypercholesterolemia. N. Engl. J. Med. 2020;383(8):711–720. DOI: 10.1056/NEJMoa2004215.

151. Gill P.K., Hegele R.A. New biological therapies for low-density lipoprotein cholesterol. Can. J. Cardiol. 2023;39(12):1913–1930. DOI:10.1016/j.cjca.2023.08.003.

152. Esba L.C.A., Alharbi H. Lomitapide: a medication use evaluation and a formulary perspective. Glob. J. Qual. Saf. Healthc. 2024;7(2):59–62. DOI: 10.36401/JQSH-23-32.

153. Dybiec J., Baran W., Dąbek B., Fularski P., Młynarska E., Radzioch E. et al. Advances in treatment of dyslipidemia. Int. J. Mol. Sci. 2023;24(17):13288. DOI: 10.3390/ijms241713288.

154. Soppert J., Lehrke M., Marx N., Jankowski J., Noels H. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting. Adv. Drug Deliv. Rev. 2020;159:4–33. DOI: 10.1016/j.addr.2020.07.019.

155. Bagheri Kholenjani F., Shahidi S., Vaseghi G., Ashoorion V., Sarrafzadegan N., Siavash M. et al. First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults. J. Res. Med. Sci. 2024;29:18. DOI: 10.4103/jrms.jrms_318_23.

156. Leung Y.Y., Yao Hui L.L., Kraus V.B. Colchicine—Update on mechanisms of action and therapeutic uses. Semin. Arthritis Rheum. 2015;45(3):341–350. DOI: 10.1016/j.semarthrit.2015.06.013.

157. Zhou H., Khan D., Gerdes N., Hagenbeck C., Rana M., Cornelius J.F. et al. Colchicine protects against ethanol-induced senescence and senescence-associated secretory phenotype in endothelial cells. Antioxidants (Basel). 2023;12(4):960. DOI: 10.3390/antiox12040960.

158. Aldana-Bitar J., Golub I.S., Moore J., Krishnan S., Verghese D., Manubolu V.S. et al. Colchicine and plaque: a focus on atherosclerosis imaging. Prog. Cardiovasc. Dis. 2024;84:68–75. DOI: 10.1016/j.pcad.2024.02.010.

159. Tucker B., Goonetilleke N., Patel S., Keech A. Colchicine in atherosclerotic cardiovascular disease. Heart. 2024;110(9):618–625. DOI: 10.1136/heartjnl-2023-323177.

160. Zhang F.S., He Q.Z., Qin C.H., Little P.J., Weng J.P., Xu S.W. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol. Sin. 2022;43(9):2173–2190. DOI: 10.1038/s41401-021-00835-w.

161. Tardif J.C., Kouz S., Waters D.D., Bertrand O.F., Diaz R., Maggioni A.P. et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N. Engl. J. Med. 2019;381(26):2497–2505. DOI: 10.1056/NEJMoa1912388.

162. Nidorf S.M., Fiolet A.T.L., Mosterd A., Eikelboom J.W., Schut A., Opstal T.S.J. et al. Colchicine in patients with chronic coronary disease. N. Engl. J. Med. 2020;383(19):1838–1847. DOI: 10.1056/NEJMoa2021372.

163. Bresson D., Roubille F., Prieur C., Biere L., Ivanes F., Bouleti C. et al. Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol – The COVERT-MI Study. Cardiology. 2021;146(2):151–160. DOI: 10.1159/000512772.

164. Kelly P., Lemmens R., Weimar C., Walsh C., Purroy F., Barber M. et al. Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial. Lancet. 2024;404(10448):125–133. DOI: 10.1016/S0140-6736(24)00968-1.

165. Fogacci F., Al Ghasab N.S., Di Micoli V., Giovannini M., Cicero A.F.G. Cholesterol-lowering bioactive foods and nutraceuticals in pediatrics: clinical evidence of efficacy and safety. Nutrients. 2024;16(10):1526. DOI: 10.3390/nu16101526.

166. Cicero A.F.G., Fogacci F. The year in nutrition medicine 2023. Arch. Med. Sci. 2023;19(6):1599–1601. DOI: 10.5114/aoms/174787.

167. Sesso H.D., Manson J.E., Aragaki A.K., Rist P.M., Johnson L.G., Friedenberg G. et al. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am. J. Clin. Nutr. 2022;115(6):1490–1500. DOI: 10.1093/ajcn/nqac055.

168. Osadnik T., Goławski M., Lewandowski P., Morze J., Osadnik K., Pawlas N. et al. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol. Res. 2022;183:106402. DOI: 10.1016/j.phrs.2022.106402.