Возрастные особенности основных факторов риска и клинико-лабораторных показателей у мужчин 30–50 лет с атеротромботическим инсультом

Введение. Ишемический инсульт у пациентов моложе 50 лет не является редкостью. Распространенность инсульта в молодом возрасте увеличивается из-за увеличения факторов риска. Раннее выявление факторов риска и оптимизация первичной и вторичной профилактической терапии являются обязательными для снижения бремени инсульта среди молодых людей и сохранения потенциальных лет жизни.

Цель. Выявить и оценить основные факторы риска и клинико-лабораторные показатели у мужчин в возрасте 31–40 лет и 41–50 лет с атеротромботическим инсультом.

Материалы и методы. До развития пандемии COVID-19 было обследовано 60 пациентов (средний возраст – 43,3±3,8 года). Всем проводились нейровизуализация головного мозга, ультразвуковое исследование магистральных сосудов головы, ЭхоКГ, ЭКГ, лабораторное исследование сыворотки крови.

Результаты. Среди всех пациентов в возрасте 31–40 лет было 10 пациентов (средний возраст – 37,4±2,6 года) и в возрасте 41–50 лет – 50 пациентов (средний возраст – 44,5±2,8 года). У всех пациентов отмечалось атеросклеротическое поражение магистральных артерий головы, причем стенозы более 70 % только у пациентов в возрасте 41–50 лет. Среди пациентов в возрасте 31–40 лет и 41–50 лет среди других факторов риска наиболее часто выявлялись артериальная гипертензия (90 и 72 %), курение (70 и 72 %), дислипидемия (66,7 и 60 %) и регулярное употребление алкоголя (30 и 36 %). В исследовании отмечены статистически значимые корреляции основных сосудистых факторов риска с сывороточными показателями липидного обмена, гемостаза и маркерами эндотелиальной дисфункции.

Выводы. В проведенном исследовании показана частота встречаемости основных факторов риска у пациентов с атеротромботическим инсультом в возрасте 31–40 лет и 41–50 лет, а также роль нарушений липидного обмена, гемостазиологических нарушений и эндотелиальной дисфункции в их развитии.

1. Bennett JE, Stevens GA, Mathers CD, Bonita R, Rehm J, Kruk M. et al. NCD Countdown 2030: worldwide trends in non-communicable disease mortality and progress towards sustainable development goal target 3.4. Lancet. 2018 Sep 22; 392 (10152): 1072–1088. DOI: 10.1016/S0140–6736(18)31992-5

2. King D, Wittenberg R, Patel A, Quayyum Z, Berdunov V, Knapp M. The future incidence, prevalence and costs of stroke in the UK. Age Ageing 2020; 49: 277–82. DOI: 10.1093/ageing/afz163

3. GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021 Oct; 20 (10): 795–820. DOI: 10.1016/S1474–4422(21)00252-0

4. Ekker M.S., Boot E. M., Singhal A. B., Tan K. S., Debette S., Tuladhar A. M. et al. Epidemiology, aetiology, and management of ischaemic stroke in young adults. Lancet Neurol. 2018; 17: 790–801. DOI: 10.1016/S1474–4422(18)30233-3

5. Maaijwee NA, Rutten-Jacobs LC, Schaapsmeerders P, van Dijk EJ, de Leeuw FE. Ischaemic stroke in young adults: risk factors and long-term consequences. Nat. Rev. Neurol. 2014; 10 (6): 315–325. DOI: 10.1038/nrneurol.2014.72

6. Purroy F.M.N. Epidemiología del ictus en la última década: revisión sistemática. Rev Neurol. 2021; 73: 321–336. DOI: 10.33588/rn.7309.2021138

7. Reverté-Villarroya S, Suñer-Soler R, Sauras-Colón E, Zaragoza-Brunet J, Fernández-Sáez J, Lopez-Espuela F. Ischemic stroke and vascular risk factors in young and older adults. Community-based retrospective study (2011–2020). Aten Primaria. 2023 Jun; 55 (6): 102623. DOI: 10.1016/j.aprim.2023.102623

8. Ohya Y., Matsuo R., Sato N., Irie F., Nakamura K., Wakisaka Y. et al. Causes of ischemic stroke in young adults versus non-young adults: A multicenter hospital-based observational study. PLoS One. 2022; 17: 1–20. DOI: 10.1371/journal.pone.0268481

9. Purroy F, Vena A, Forne C, de Arce AM, Davalos A, Fuentes B. et al. Age- and sex-specific risk profiles and in-hospital mortality in 13,932 Spanish stroke patients. Cerebrovasc Dis. 2019; 47: 151–64. DOI: 10.1159/000500205

10. Cordonnier C, Sprigg N, Sandset EC, Pavlovic A, Sunnerhagen KS, Caso V. et al. Stroke in women – from evidence to inequalities. Nat. Rev. Neurol. 2017; 13: 521–32. DOI: 10.1038/nrneurol.2017.95.

11. Béjot Y., Duloquin G., Graber M., Garnier L., Mohr S., Giroud M. Current characteristics and early functional outcome of older stroke patients: A population-based study (Dijon Stroke Registry) Age Ageing. 2021; 50: 898–905. DOI: 10.1093/ageing/afaa192

12. Skajaa N., Adelborg K., Horváth-Puhó E., Rothman K. J., Henderson V. W., Casper Thygesen L. et al. Nationwide trends in incidence and mortality of stroke among younger and older adults in Denmark. Neurology. 2021; 96: e1711–e1723. DOI: 10.1212/WNL.0000000000011636

13. Adams HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE. Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Stroke. 1993 Jan; 24 (1): 35–41. DOI: 10.1161/01.str.24.1.35

14. Максимова М. Ю., Сазонова В. Ю. Факторы риска развития ишемического инсульта у мужчин и женщин в возрасте 45–74 лет. Неврология, нейропсихиатрия, психосоматика. 2023; 15 (4): 38–44. https://doi.org/10.14412/2074-2711-2023-4-38-44

15. Zhernossekov DD, Zolotareva EN, Kondratuk AS. Structural and functional peculiarities of plasminogen activator inhibitor PAI-1. Biopolymers and Cell. 2010; 26 (4): 255–264. Available at: https://www.researchgate.net/publication/46105902_Structural_and_functional_peculiarities_of_plasminogen_activator_inhibitor_PAI-1.

16. Hov GG, Sagen E, Bigonah A, Asberg A. Health-associated reference values for arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) measured with high-performance liquid chromatography. Scand. J. Clin. Lab. Invest. 2007; 67 (8): 868–76. DOI: 10.1080/00365510701429836

17. Putaala J, Metso AJ, Metso TM. et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki Young Stroke Registry. Stroke. 2009; 40: 1195–1203. DOI: 10.1161/STROKEAHA.108.529883

18. Zhang YN, He L. Risk factors study of ischemic stroke in young adults in Southwest China. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012; 43: 553–557. https://pubmed.ncbi.nlm.nih.gov/22997895/

19. Wu TY, Kumar A, Wong EH. Young ischaemic stroke in South Auckland: a hospital-based study. N Z Med. J. 2012; 125: 47–56. https://pubmed.ncbi.nlm.nih.gov/23242397/

20. Stanaway J.D., Afshin A., Gakidou E., Lim S. S., Abate D., Abate K. H. et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Stu. Lancet. 2018; 392: 1923–1994. DOI: 10.1016/S0140–6736(18)32225-6

21. Park JH, Ovbiagele B, Hong KS, Kwon SU. Association of Systolic Blood Pressure with Progression of Symptomatic Intracranial Atherosclerotic Stenosis. J. Stroke. 2017; 19: 304–311. DOI: 10.5853/jos.2017.00136

22. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360: 1903–1913. DOI: 10.1016/s0140–6736(02)11911-8

23. Wang C., Yuan Y., Zheng M., Pan A., Wang M., Zhao M. et al. Association of age of onset of hypertension with cardiovascular diseases and mortality. J. Am. Coll. Cardiol. 2020; 75: 2921–2930. DOI: 10.1016/j.jacc.2020.04.038

24. National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. The health consequences of smoking – 50 years of progress: a report of the Surgeon General. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; Atlanta, GA, US: 2014. https://pubmed.ncbi.nlm.nih.gov/24455788/

25. Chan KH, Wright N, Xiao D, Guo Y, Chen Y, Du H. et al. China Kadoorie Biobank collaborative group. Tobacco smoking and risks of more than 470 diseases in China: a prospective cohort study. Lancet Public Health. 2022 Dec; 7 (12): e1014–e1026. DOI: 10.1016/S2468–2667(22)00227-4

26. Meza R, Cao P, Jeon J, Warner KE, Levy DT. Meza R, Cao P, Jeon J, Warner KE, Levy DT. Trends in US Adult Smoking Prevalence, 2011 to 2022. JAMA Health Forum. 2023 Dec 1; 4 (12): e234213. DOI: 10.1001/jamahealthforum.2023.4213

27. Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nat. Rev. Genet. 2009; 10: 109–121. DOI: 10.1038/nrg2481

28. Shah AS, Wilson DP. Primary hypertriglyceridemia in children and adolescents. J. Clin. Lipidol. 2015; 9: S 20–S 28. DOI: 10.1016/j.jacl.2015.04.004

29. Ding W, Dong H, Mi J. Prevalence of dyslipidemia in chinese children and adolescents: a meta-analysis. Zhonghua Liu Xing Bing Xue Za Zhi. 2015; 36: 71–77. https://pubmed.ncbi.nlm.nih.gov/25876870/

30. Arora S, Stouffer GA, Kucharska-Newton AM, Qamar A, Vaduganathan M, Pandey A. et al. Twenty year trends and sex differences in young adults hospitalized with acute myocardial infarction. Circulation. 2019; 139: 1047–1056. DOI: 10.1161/CIRCULATIONAHA.118.037137

31. Andersson C, Vasan RS. Epidemiology of cardiovascular disease in young individuals. Nat. Rev. Cardiol. 2018; 15: 230–240. DOI: 10.1038/nrcardio.2017.154

32. Freiberg JJ, Tybjærg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA. 2008; 300: 2142–2152. DOI: 10.1001/jama.2008.621

33. Varona JF, Guerra JM, Bermejo F, Molina JA, Gomez A. Causes of ischemic stroke in young adults, and evolution of the etiological diagnosis over the long term. Eur. Neurol. 2007; 57 (4): 212–218. DOI: 10.1159/000099161

34. Spengos K, Vemmos K. Risk factors, etiology, and outcome of first-ever ischemic stroke in young adults aged 15 to 45 – the Athens young stroke registry. Eur. J. Neurol. 2010; 17 (11): 1358–1364. DOI: 10.1111/j.1468–1331.2010.03065.x

35. Khan FY. Risk factors of young ischemic stroke in Qatar. Clin Neurol Neurosurg. 2007; 109 (9): 770–773. DOI: 10.1016/j.clineuro.2007.07.006

36. Schwarzwald A, Fischer U, Seiffge D, Beyeler M, Scutelnic A, Kaesmacher J. et al. Impact of sex in stroke in the young. PLoS One. 2023 Mar 31; 18 (3): e0274722. DOI: 10.1371/journal.pone.0274722

37. GBD 2020 Alcohol Collaborators. Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020. Lancet. 2022 Jul 16; 400 (10347): 185–235. DOI: 10.1016/S0140–6736(22)00847-9

38. Lee NT, Ong LK, Gyawali P, Nassir CMNCM, Mustapha M, Nandurkar HH, Sashindranath M. Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease. Biomolecules. 2021 Jul 6; 11 (7): 994. DOI: 10.3390/biom11070994

39. Goslawski M, Piano MR, Bian JT, Church EC, Szczurek M, Phillips SA. Binge drinking impairs vascular function in young adults. J. Am. Coll. Cardiol. 2013; 62: 201–207. DOI: 10.1016/j.jacc.2013.03.049

40. Hamburg NM, Keyes MJ, Larson MG, Vasan RS, Schnabel R, Pryde MM, Mitchell GF, Sheffy J, Vita JA, Benjamin EJ. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart study. Circulation. 2008; 117: 2467–2474. DOI: 10.1161/CIRCULATIONAHA.107.748574

41. Dirnagl U., Iadecola C., Moskowitz M. A. Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci. 1999; 22: 391–397. DOI: 10.1016/S0166–2236(99)01401-0

42. Dirnagl U. Pathobiology of injury after stroke: The neurovascular unit and beyond. Ann. N. Y. Acad. Sci. 2012; 1268: 21–25. DOI: 10.1111/j.1749–6632.2012.06691.x

43. Hu X., De Silva T. M., Chen J., Faraci F. M. Cerebral vascular disease and neurovascular injury in ischemic stroke. Circ. Res. 2017; 120: 449–471. DOI: 10.1161/CIRCRESAHA.116.308427

44. Nakagomi T., Kassell N., Sasaki T., Fujiwara S., Lehman R., Torner J. Impairment of endothelium-dependent vasodilation induced by acetylcholine and adenosine triphosphate following experimental subarachnoid hemorrhage. Stroke. 1987; 18: 482–489. DOI: 10.1161/01.STR.18.2.482

45. Constans J, Conri C. Circulating markers of endothelial function in cardiovascular disease. Clin Chim Acta. 2006; 368: 33–47. DOI: 10.1016/j.cca.2005.12.030

46. Hassan A, Hunt BJ, O'Sullivan M. et al. Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis. Brain. 2003; 126: 424–432. DOI: 10.1093/brain/awg040

47. Kario K, Matsuo T, Kobayashi H, Hoshide S, Shimada K. Hyperinsulinemia and hemostatic abnormalities are associated with silent lacunar cerebral infarcts in elderly hypertensive subjects. J. Am. Coll. Cardiol. 2001; 37: 871–877. DOI: 10.1016/s0735–1097(00)01172-4

48. Hamsten A., Wiman B., De Faire U., Blombäck M. Increased Plasma Levels of a Rapid Inhibitor of Tissue Plasminogen Activator in Young Survivors of Myocardial Infarction. N. Engl. J. Med. 1985; 313: 1557–1563. DOI: 10.1056/NEJM198512193132501

49. Tofler G., Massaro J., O’Donnell C., Wilson P., Vasan R., Sutherland P., Meigs J., Levy D., D’Agostino R. Plasminogen activator inhibitor and the risk of cardiovascular disease: The Framingham Heart Study. Thromb. Res. 2016; 140: 30–35. DOI: 10.1016/j.thromres.2016.02.002

50. Jung R.G., Motazedian P., Ramirez F. D., Simard T., Di Santo P., Visintini S. et al. Association between plasminogen activator inhibitor-1 and cardiovascular events: A systematic review and meta-analysis. Thromb. J. 2018; 16: 1–12. DOI: 10.1186/s12959-018-0166-4

51. Song C., Burgess S., Eicher J. D., O’Donnell C.J., Johnson A. D., Huang J., Sabater-Lleal M., Asselbergs F. W., Tregouet D., Shin S. et al. Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. J. Am. Heart Assoc. 2017; 6. DOI: 10.1161/JAHA.116.004918

52. Schneiderman J., Sawdey M. S., Keeton M. R., Bordin G. M., Bernstein E. F., Dilley R. B., Loskutoff D. J. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc. Natl. Acad. Sci. USA. 1992; 89: 6998–7002. DOI: 10.1073/pnas.89.15.6998

53. Chomiki N., Henry M., Alessi M. C., Anfosso F., Juhan-Vague I. Plasminogen Activator Inhibitor-1 Expression in Human Liver and Healthy or Atherosclerotic Vessel Walls. Thromb. Haemost. 1994; 72: 44–53. DOI: 10.1055/s-0038–1648809

54. Zhang J. Biomarkers of endothelial activation and dysfunction in cardiovascular diseases. Rev Cardiovasc Med. 2022 Feb 22; 23 (2): 73. DOI: 10.31083/j.rcm2302073

55. Dowsett L, Higgins E, Alanazi S, Alshuwayer NA, Leiper FC, Leiper J. ADMA: A Key Player in the Relationship between Vascular Dysfunction and Inflammation in Atherosclerosis. J Clin Med. 2020 Sep 20; 9 (9): 3026. DOI: 10.3390/jcm9093026