Assessment of Biomarker Profile in Patients Post Carotid Angioplasty and Stenting

Abstract

Introduction. Cardiovascular diseases are predominantly caused by atherosclerosis as a multifactorial chronic condition. Alterations in the hematological system and the blood vessel wall are considered as highly significant for onset and development of cerebrovascular disorders associated with atherosclerosis. Biomarkers as measurable indicators are to verify abnormal activity.

Objective: to assess atherogenesis biomarkers in patients after carotid angioplasty and stenting (CAS) as associated with development of cerebrovascular disease.

Materials and methods. We evaluated 50 individuals (50% men, 50% women; average age 65.4 ± 6.4 years) with established cerebrovascular disease associated with brain atherosclerosis. All of them had hemodynamically significant abnormalities in the internal carotid artery (ICA) with both symptomatic (stenosis 60% and more) and asymptomatic (stenosis 70% and more) stenoses confirmed by duplex scanning of the brachiocephalic arteries. All patients underwent CAS as indicated. Before and 1 year after the intervention, we performed clinical and neurological examinations, brain magnetic resonance imaging, and laboratory tests of atherogenesis biomarkers.

Results. At baseline, all the individuals demonstrated a pro-atherogenic shift in the assessed indicators, predominantly markers of extracellular matrix degradation, inflammation and atherogenesis (including osteoprotegerin and chromogranin А). Additionally, we established a direct correlation between osteoprotegerin levels and the characteristics of mostly hyperechoic atherosclerotic plaques (r = 0.29; p < 0.05). A year later, no signs of restenosis were shown in follow-up ultrasound assessment of stented arteries in any patient.

In 1 year post CAS, we found significant changes in the levels of osteoprotegerin (decrease to 1.765 pg/mL [1.592; 1.937]; p < 0.05) and chromogranin А (elevation to 31.3 μg/L [13.9; 90.7]; p < 0.05). Re-assessment demonstrated association between changes in the pattern of the nitrogen oxide system, which tends to improve (NO elevation to 38.23 μmol/L [32.95; 43.51]; p < 0.001), and atheroprotective shift in the morphology of atherosclerotic plaques and biomarker profile.

Conclusion. Prospective, 1-year long observation for patients who underwent CAS for symptomatic/asymptomatic hemodynamically significant ICA stenoses revealed favourable atheroprotective shift in both ultrasound and hematological atherogenesis biomarker ratio. This shift contributed to the absence of cerebral atherosclerosis progression during the follow-up. The process may be mediated by chromogranin А and osteoprotegerin, and their further research is needed from perspective of atherogenesis.

About the authors

Мarine М. Tanashyan

Research Center of Neurology

Email: mtanashyan@neurology.ru
ORCID iD: 0000-0002-5883-8119

D. Sci. (Med.), Professor, Corresponding member of RAS, Deputy Director for science, Head, 1st Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Vladislav A. Annushkin

Research Center of Neurology

Author for correspondence.
Email: annushkin@neurology.ru
ORCID iD: 0000-0002-9120-2550

postgraduate student, 1st Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Anton A. Raskurazhev

Research Center of Neurology

Email: rasckey@live.com
ORCID iD: 0000-0003-0522-767X

Cand. Sci. (Med.), neurologist, researcher, 1st Neurology department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Olga V. Lagoda

Research Center of Neurology

Email: olga.lagoda@gmail.com
ORCID iD: 0000-0001-7562-4991

Cand. Sci. (Med.), senior researcher, 1st Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Аlla A. Shabalina

Research Center of Neurology

Email: ashabalina@yandex.ru
ORCID iD: 0000-0001-9604-7775

D. Sci. (Med.), leading researcher, Head, Laboratory of hemorheology, hemostasis and pharmacokinetics (with clinical laboratory diagnostics)

Russian Federation, Moscow

Roman B. Medvedev

Research Center of Neurology

Email: medvedev-roman@yandex.ru
ORCID iD: 0000-0003-3887-0418

Cand. Sci. (Med.), researcher, 1st Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Vladimir L. Shchipakin

Research Center of Neurology

Email: vladshchipakin@gmail.com
ORCID iD: 0000-0003-1428-2769

Cand. Sci. (Med.), Head, Group of vascular and endovascular surgery, senior researcher, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

References

  1. Zorowitz R.D., Chen E., Tong K.B., Laouri M. Costs and rehabilitation use of stroke survivors: a retrospective study of Medicare beneficiaries. Top. Stroke Rehabil. 2009;16(5):309–320. doi: 10.1310/tsr1605-309
  2. Танашян М.М., Лагода О.В., Гулевская Т.С. и др. Прогрессирующий церебральный атеросклероз: клинические, биохимические и морфологические аспекты. Анналы клинической и экспериментальной неврологии. 2013;7(4):4–9. Tanashyan M.M., Lagoda O.V., Gulevskaya T.S. et al. Progressive cerebral atherosclerosis: clinical, biochemical, and morphological aspects. Annals of Clinical and Experimental Neurology. 2013;7(4):4–9. (In Russ.)
  3. Суслина З.А., Танашян М.М., Ионова В.Г. Ишемический инсульт: кровь, сосудистая система, антитромботическая терапия. М.; 2005. Suslina Z.A., Tanashyan M.M., Ionova V.G. Ischemic stroke: blood, vascular system, antithrombotic therapy. Moscow; 2005. (In Russ.)
  4. Дон Е.С., Тарасов А.В., Эпштейн О.И., Тарасов С.А. Биомаркеры в медицине: поиск, выбор, изучение и валидация. Клиническая лабораторная диагностика. 2017;62(1):52–59. Don E.S., Tarasov A.V., Epshtein O.I., Tarasov S.A. The biomarkers in medicine: search, choice, study and validation. Russian Clinical Laboratory Diagnoistics. 2017;62(1):52–59. (In Russ.). doi: 10.18821/0869-2084-2017-62-1-52-59
  5. Евдокименко А.Н., Чечеткин А.О., Друина Л.Д., Танашян М.М. Оценка неоваскуляризации атеросклеротической бляшки каротидного синуса с помощью контраст-усиленного УЗИ. Вестник РГМУ. 2019;(4):25–33. Evdokimenko A.N., Chechetkin A.O., Druina L.D., Tanashyan M.M. Evalua- tion of neovascularization of atherosclerotic plaque of the carotid sinus using contrast-enhanced ultrasound. Bulletin of RSMU. 2019;(4):25–33. (In Russ.). doi: 10.24075/vrgmu.2019.057
  6. Щербак С.Г., Лисовец Д.Г., Сарана А.М. и др. Биомаркеры сердечно-сосудистых заболеваний. Физическая и реабилитационная медицина, медицинская реабилитация. 2019;1(2):60–76. Scherbak S.G., Lisovets D.G., Sarana A.M. et al. Biomarkers of cardiovascular disease. Physical and rehabilitation medicine, medical rehabilitation. 2019;1(2):60–76. (In Russ.). doi: 10.36425/2658-6843-19190
  7. Naka K.K., Bechlioullis A., Marini A. Interleukin-1 genotypes modulate the long-term effect of lipoprotein(a) on cardiovascular events: The Ioannina Study. J. Clin. Lipidol. 2018;12(2):338–347. doi: 10.1016/j.jacl.2017.12.004
  8. Berntsson J., Östling G., Persson M. et al. Carotid plaque, and incidence of stroke. Stroke. 2016;47(7):1858–1863. doi: 10.1161/STROKEAHA.116.013374
  9. Kokkinos J., Tang S., Rye K.A., Ong K.L. The role of fibroblast growth factor 21 in atherosclerosis. Atherosclerosis. 2017;257:259–265. doi: 10.1016/j.atherosclerosis.2016.11.033
  10. Cao Y., Cui C., Zhao H. et al. Plasma osteoprotegerin correlates with stroke severity and the occurrence of microembolic signals in patients with acute ischemic stroke. Dis. Markers. 2019:3090364. doi: 10.1155/2019/3090364
  11. Mahata S.K., Corti A. Chromogranin A and its fragments in cardiovascular, immunometabolic, and cancer regulation. Ann. N. Y. Acad. Sci. 2019;1455(1):34–58. doi: 10.1111/nyas.14249
  12. Wang J., Bai X., Wang T. et al. Carotid stenting versus endarterectomy for asymptomatic carotid artery stenosis: a systematic review and meta-analysis. Stroke. 2022;53(10):3047–3054. doi: 10.1161/STROKEAHA.122.038994
  13. Saw J. Carotid artery stenting for stroke prevention. Can. J. Cardiol. 2014;30(1):22–34. doi: 10.1016/j.cjca.2013.09.030
  14. Hwang S.J., Ballantyne C.M., Sharrett A.R. et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation. 1997;96(12):4219–4225. doi: 10.1161/01.cir.96.12.4219
  15. Wu Y.W., Yang W.S., Chen M.F. et al. High serum level of matrix metalloproteinase-1 and its rapid surge after intervention in patients with significant carotid atherosclerosis. J. Formos. Med. Assoc. 2008;107(1):93–98. doi: 10.1016/S0929-6646(08)60015-7
  16. Nagy B., Woth G., Mérei Á. Perioperative time course of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor TIMP-1 & S100B protein in carotid surgery. Indian J. Med. Res. 2016;143(2):220–226. doi: 10.4103/0971-5916.180212
  17. Mérei Á., Nagy B., Woth G. et al. Comparison of the perioperative time courses of matrix metalloproteinase-9 (MMP-9) and its inhibitor (TIMP-1) during carotid artery stenting (CAS) and carotid endarterectomy (CEA). BMC Neurol. 2018;18(1):128. doi: 10.1186/s12883-018-1133-1
  18. Максюткина Л.Н. Цереброваскулярные заболевания и церебральный атеросклероз: биомаркеры воспаления: автореф. дис. … к.м.н. М.; 2013. 28 c. Maksyutkina L.N. Cerebrovascular disease and cerebral atherosclerosis: biomarkers of inflammation: Abstract for the Thesis med. sci. degree. Moscow; 2013. 28 p. (In Russ.)
  19. Танашян М.М., Медведев Р.Б., Гемджян Э.Г. и др. Патент РФ на изобретение № 2786477 «Способ прогнозирования состава эмболического материала в системе дистальной противоэмболической защиты мозга после транслюминальной баллонной ангиопластики со стентированием внутренней сонной артерии». 2022. Tanashyan M.M., Medvedev R.B., Gemdzhyan E.G. et al. RF Patent No 2786477 for invention “A method for predicting the composition of embolic material in the system of distal anti-embolic protection of the brain after transluminal balloon angioplasty with stenting of the internal carotid artery.” 2022 (In Russ.)
  20. Reiter M., Effenberger I., Sabeti S. et al. Increasing carotid plaque echolucency is predictive of cardiovascular events in high-risk patients. Radiology. 2008;248(3):1050–1055. doi: 10.1148/radiol.2483071817
  21. Bonati L.H., Gregson J., Dobson J. Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trial. Lancet Neurol. 2018;17(7):587–596. doi: https://doi.org/10.1016/S1474-4422(18)30195-9
  22. Raskurazhev A.A., Kuznetsova P.I., Shabalina A.A., Tanashyan M.M. MicroRNA and hemostasis profile of carotid atherosclerosis. Int. J. Mol. Sci. 2022;23(18):10974. doi: 10.3390/ijms231810974
  23. Atiq F., van de Wouw J., Sorop O. et al. Endothelial dysfunction, atherosclerosis, and increase of von Willebrand Factor and Factor VIII: a randomized controlled trial in Swine. Thromb. Haemost. 2021;121(5):676–686. doi: 10.1055/s-0040-1722185
  24. Liu Y., Yu H., Zhang Y., Zhao Y. TLRs are important inflammatory factors in atherosclerosis and may be a therapeutic target. Med. Hypotheses. 2008;70(2):314–316. doi: 10.1016/j.mehy.2007.05.030
  25. Kwon A., Choi Y.S., Choi Y.W. et al. Serum osteoprotegerin is associated with calcified carotid plaque: a strobe-compliant observational study. Medicine (Baltimore). 2016;95(15):3381. doi: 10.1097/MD.0000000000003381
  26. Kadoglou N.P., Gerasimidis T., Kapelouzou A. et al. Beneficial changes of serum calcification markers and contralateral carotid plaques echogenicity after combined carotid artery stenting plus intensive lipid-lowering therapy in patients with bilateral carotid stenosis. Eur. J. Vasc. Endovasc. Surg. 2010;39(3):258–265. doi: 10.1016/j.ejvs.2009.11.013
  27. Lindberg G., Råstam L., Nilsson-Ehle P. et al. Serum sialic acid and sialoglycoproteins in asymptomatic carotid artery atherosclerosis. ARIC Investigators. Atherosclerosis risk in communities. Atherosclerosis. 1999;146(1):65–69. doi: 10.1016/s0021-9150(99)00130-6
  28. Евдокименко А.Н., Куличенкова К.Н., Гулевская Т.С., Танашян М.М. Особенности регуляции ангиогенеза в атеросклеротических бляшках каротидного синуса на поздних стадиях развития атеросклероза. Российский физиологический журнал им. И.М. Сеченова. 2022;108(5):649–666. Evdokimenko A.N., Kulichenkova K.N., Gulevskaya T.S., Tanashyan M.M. Defining characteristics of angiogenesis regulation in advanced human carotid plaques. Russian Journal of Physiology. 2022;108(5):649–666. (In Russ.). doi: 10.31857/S086981392205004
  29. Быковская М.А., Раскуражев А.А., Шабалина А.А. и др. Биомаркеры повреждения сосудистой стенки у пациентов с цереброваскулярными заболеваниями и сахарным диабетом 2-го типа. Тромбоз, гемостаз и реология. 2021;(2):80–86. Bykovskaya M.A., Raskurazhev A.A., Shabalina A.A. et al. Biomarkers of vascular wall damage in patients with cerebrovascular diseases and type 2 diabetes mellitus. Thrombosis, hemostasis and rheology. 2021;(2):80–86. (In Russ.). doi: 10.25555/THR.2021
  30. Танашян М.М., Раскуражев А.А., Шабалина А.А. и др. Биомаркеры церебрального атеросклероза: возможности ранней диагностики и прогнозирования индивидуального риска. Анналы клинической и экспериментальной неврологии. 2015;9(3):20–25. Tanashyan M.M., Raskurazhev A.A., Shabalina A.A., et al. Biomarkers of cerebral atherosclerosis: the capabilities of early diagnosis and prognosis of individual risk. Annals of Clinical and Experimental Neurology. 2015;9(3):20–25. (In Russ.). doi: 10.17816/psaic141
  31. Zhu Y., Xian X., Wang Z. Research progress on the relationship between atherosclerosis and inflammation. Biomolecules. 2018;8(3):80. doi: 10.3390/biom8030080.
  32. Mazza R., Gattuso A., Mannarino C. et al. Catestatin (chromogranin A344-364) is a novel cardiosuppressive agent: inhibition of isoproterenol and endothelin signaling in the frog heart. Am. J. Physiol. Heart Circ. Physiol. 2008;295(1):113–122. doi: 10.1152/ajpheart.00172.2008
  33. Helle K.B., Corti A., Metz-Boutigue M.H., Tota B. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol. Life Sci. 2007;64(22):2863–2886. doi: 10.1007/s00018-007-7254-0
  34. Watanabe T. The emerging roles of chromogranins and derived polypeptides in atherosclerosis, diabetes, and coronary heart disease. Int. J. Mol. Sci. 2021;22(11):6118. doi: 10.3390/ijms22116118
  35. Bachetti T., Ferrari Bardile A., Aloi T.L. et al. Plasma levels of vasostatin-1, a chromogranin A fragment, are associated with carotid artery maximum stenosis: a pilot study. Int. J. Cardiol. 2017;236:438–443. doi: 10.1016/j.ijcard.2017.02.019

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Biomarker correlation before (А) and one year after (В) CAS (p < 0.05). The square area is proportional to the correlation coefficient while their color depends on the relationship direction.

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Copyright (c) 2023 Tanashyan М.М., Annushkin V.A., Raskurazhev A.A., Lagoda O.V., Shabalina А.A., Medvedev R.B., Shchipakin V.L.

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