Role of intercellular aggregates and oxidative stress markers in assessment of cardiovascular outcomes in patients after coronary artery bypass grafting
https://doi.org/10.29001/2073-8552-2025-40-4-101-112
Abstract
Aim: To compare the levels of C-reactive protein (CRP), circulating cell aggregates (including P-selectin-expressing aggregates), lipid profiles, and platelet chemiluminescence activity in patients with and without adverse cardiovascular events following coronary artery bypass grafting (CABG).
Material and Methods. The study enrolled 102 patients with angina pectoris (functional class II–IV) who underwent CABG. Prior to CABG, comprehensive blood analysis and lipid profile assessment were performed. Both preand postoperatively, platelet chemiluminescence and flow cytometry analyses were conducted. Composite endpoints (worsening angina class, progression of heart failure, myocardial infarction, stroke, cardiovascular death, or repeat revascularization) were evaluated during hospitalization (8–10 days post-CABG) and at 23.3 ± 7.6 months postoperatively.
Results. Composite endpoints occurred in 16 patients. Significant differences were observed between groups (no events vs. adverse outcomes). Pre-CABG: monocyte-platelet aggregates: 13.4% [5.9; 24.2] vs. 34.9% [19.05; 50.25], p = 0.001; Mean fluorescence intensity (MFI) of P-selectin-expressing neutrophil-platelet aggregates: 4.85 AU [2.99; 8.79] vs. 12.5 AU [5.09; 15.3], p = 0.005; MFI of P-selectin-expressing monocyte-platelet aggregates: 4.27 AU [2.6; 7.76] vs. 9.53 AU [6.68; 14.8], p = 0.006. Post-CABG: P-selectin-expressing neutrophil-platelet aggregates: 75.7% [62.36; 90.54] vs. 92.3% [80; 99.29], p = 0.027. The median time to peak lucigenin-enhanced platelet chemiluminescence pre-CABG was significantly shorter in patients with adverse events compared to event-free patients (212 s [53; 621] vs. 885 s [257.75; 2087], p = 0.032). Similarly, the median time to peak spontaneous neutrophil chemiluminescence with lucigenin was reduced in the adverse events group (847 s [565; 1018] vs. 1355 s [1065.5; 1898.5], p = 0.017).
Conclusion. Patients with composite adverse cardiovascular events exhibited significantly different MFI and platelet-leukocyte aggregate counts (preand post-CABG), pre-operative platelet/neutrophil chemiluminescence peak times, and cardiopulmonary bypass durations compared to event-free patients. These parameters may serve as predictive biomarkers for post-CABG cardiovascular risk and warrant further investigation.
Keywords
About the Authors
A. A. KosinovaРоссия
Alexandra A. Kosinova - Senior Research Scientist, Laboratory of Digital Controlled Medicines and Theranostics, KSC SB RAS; Associate Professor, Department of Therapy, Institute of Postgraduate Education, KrasSMU.
50, Akademgorodok, Krasnoyarsk, 660036; 1, Partizana Zheleznyaka str., Krasnoyarsk, 660022
Yu. I. Grinshtein
Россия
Yuriy I. Grinshtein - Dr. Sci. (Med.), Professor, Head of the Department of Therapy, Institute of Postgraduate Education, KrasSMU.
1, Partizana Zheleznyaka str., Krasnoyarsk, 660022
A. N. Maltseva
Россия
Anna N. Maltseva - Graduate Student, Department of Therapy, Institute of Postgraduate Education, KrasSMU.
1, Partizana Zheleznyaka str., Krasnoyarsk, 660022
M. D. Goncharov
Россия
Maxim D. Goncharov - Applicant, Department of Therapy, Institute of Postgraduate Education, KrasSMU; Laboratory Physician, Federal Center for Cardiovascular Surgery.
1, Partizana Zheleznyaka str., Krasnoyarsk, 660022; 45, Karaulnaya str., Krasnoyarsk, 660020
T. S. Mongush
Россия
Taira S. Mongush - Applicant, Department of Therapy, Institute of Postgraduate Education, KrasSMU; Cardiologist, Federal Center for Cardiovascular Surgery.
1, Partizana Zheleznyaka str., Krasnoyarsk, 660022; 45, Karaulnaya str., Krasnoyarsk, 660020
A. A. Savchenko
Россия
Andrey A. Savchenko - Dr. Sci. (Med.), Professor, Head of the Department of Physiology named after Prof. A.T. Pshonik, KrasSMU; Head of the Laboratory of Cellular-Molecular Physiology and Pathology, FRC KSC SB RAS.
1, Partizana Zheleznyaka str., Krasnoyarsk, 660022; 3g, Partizana Zheleznyaka str., Krasnoyarsk, 660022
References
1. Gaudino M., Di Franco A., Bhatt D.L., Alexander J.H., Abbate A., Azzalini L., et al. The association between coronary graft patency and clinical status in patients with coronary artery disease. Eur. Heart J. 2021;42(15):1433–1441. https://doi.org/10.1093/eurheartj/ehab096
2. Mauro M.S., Finocchiaro S., Calderone D., Rochira C., Agnello F., Scalia L. et al. Antithrombotic strategies for preventing graft failure in coronary artery bypass graft. J. Thromb. Thrombolysis. 2024;57(4):547–557. https://doi.org/10.1007/s11239-023-02940-5
3. Guida G.A., Angelini G.D. Pathophysiology and mechanisms of saphenous vein graft failure. Braz. J. Cardiovasc. Surg. 2022;37:32–37. https://doi.org/10.21470/1678-9741-2022-0133
4. Buxton B.F., Hayward P.A., Raman J., Moten S.C., Rosalion A., Gordon I. et al. RAPCO Investigators. Long-Term Results of the RAPCO Trials. Circulation. 2020;142(14):1330–1338. https://doi.org/10.1161/CIRCULATIONAHA.119.045427
5. Huang J.T., Sung S.H., Hsu C.P., Chiang C.E., Yu W.C., Cheng H.M. et al. TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study. Front. Cardiovasc. Med. 2023;10:1226449. https://doi.org/10.3389/fcvm.2023.1226449
6. Tscharre M., Vogel B., Tentzeris I., Freynhofer M., Rohla M., Wojta J. et al. Prognostic impact of soluble P-selectin on long-term adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention. Thromb. Haemost. 2019;119(2):340–347. https://doi.org/10.1055/s-0038-1676563
7. Ding Z., Pothineni N.V.K., Goel A., Lüscher T.F., Mehta J.L. PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1. Cardiovasc. Res. 2020;116(5):908–915. https://doi.org/10.1093/cvr/cvz313
8. Goncharov M.D., Grinshtein Y.I., Savchenko A.A., Kosinova A.A. Molecular-metabolic features of changes in platelet sensitivity to antiplatelet therapy in patients with coronary heart disease before and after coronary artery bypass grafting. Russ. J. Cardiol. 2021;26(6):4442. (In Russ.). https://doi.org/10.15829/1560-4071-2021-4442
9. Savchenko A.A., Goncharov M.D., Grinshtein Y.I., Gvozdev I.I., Mongush T.S., Kosinova A.A. Chemiluminescent analysis of reactive oxygen species synthesis by platelets from patients with coronary heart disease. Bull. Exp. Biol. Med. 2020;169(4):535–538. (In Russ.). https://doi.org/10.1007/s10517-020-04924-4
10. Oikonomou E., Leopoulou M., Theofilis P., Antonopoulos A.S., Siasos G., Latsios G. et al. A link between inflammation and thrombosis in atherosclerotic cardiovascular diseases: clinical and therapeutic implications. Atherosclerosis. 2020;309:16–26. https://doi.org/10.1016/j.atherosclerosis.2020.07.027
11. Scialla J.J., Plantinga L.C., Kao W.H.L., Jaar B., Powe N.R., Parekh R.S. Soluble P-selectin levels are associated with cardiovascular mortality and sudden cardiac death in male dialysis patients. Am. J. Nephrol. 2011;33(3):224–230. https://doi.org/10.1159/000324517
12. Burger P.C., Wagner D.D. Platelet P-selectin facilitates atherosclerotic lesion development. Blood. 2003;101(7):2661–2666. https://doi.org/10.1182/blood-2002-07-2209
13. Pluta K, Porębska K, Urbanowicz T, Gąsecka A, OlasińskaWiśniewska A, Targoński R, et al. Platelet-leucocyte aggregates as novel biomarkers in cardiovascular diseases. Biology (Basel). 2022;11(2):224. https://doi.org/10.3390/biology11020224
14. Loguinova M., Pinegina N., Kogan V., Vagida M., Arakelyan A., Shpektor A., et al. Monocytes of different subsets in complexes with platelets in patients with myocardial infarction. Thromb. Haemost. 2018;118(11):1969–1981. https://doi.org/10.1055/s-0038-1673342
15. Brambilla M., Camera M., Colnago D., Marenzi G., De Metrio M., Giesen P.L. et al. Tissue factor in patients with acute coronary syndromes: expression in platelets, leukocytes, and platelet-leukocyte aggregates. Arterioscler Thromb Vasc Biol. 2008;28(5):947–953. https://doi.org/10.1161/ATVBAHA.107.161471
16. Dey S., Kashav R., Kohli J.K., Magoon R., ItiShri, Walian A. et al. Systemic immune-inflammation index predicts poor outcome after elective off-pump CABG: a retrospective, single-center study. J. Cardiothorac. Vasc. Anesth. 2021;35(8):2397–2404. https://doi.org/10.1053/j.jvca.2020.09.092
17. Dzhatdoeva A.A., Proskurnina E.V., Nesterova A.M., Dubinkin I.V., Gaponova T.V., Obydenny S.I. et al. Mitochondria as sources of superoxide anion radical in platelets. Biol. Membr. 2017;(6):116–123. (In Russ.). https://doi.org/10.7868/S0233475517060056
18. Jancinova V., Drabikova K., Petrikova M., Nosal R. Blood platelets decrease concentration of reactive oxygen species produced by polymorphonuclear leukocytes. Bratisl. Lek. Listy. 2004;105(7–8):250–255. PMID:15543845.
19. Goncharov M.D., Savchenko A.A., Grinshtein Y.I., Gvozdev I.I., Kosinova A.A., Mongush T.S. Aspirin resistance as a result of impaired interaction of platelets and neutrophils in patients with coronary heart disease. Ration Pharmacother Cardiol. 2021;17(1):16–22. (In Russ.). https://doi.org/10.20996/1819-6446-2021-01-07
20. Mao Z., Zhong X., Yin J., Zhao Z., Hu X., Hackett M.L. Predictors associated with stroke after coronary artery bypass grafting: a systematic review. J. Neurol. Sci. 2015;357(1–2):1–7. https://doi.org/10.1016/j.jns.2015.07.006
Review
For citations:
Kosinova A.A., Grinshtein Yu.I., Maltseva A.N., Goncharov M.D., Mongush T.S., Savchenko A.A. Role of intercellular aggregates and oxidative stress markers in assessment of cardiovascular outcomes in patients after coronary artery bypass grafting. Siberian Journal of Clinical and Experimental Medicine. 2025;40(4):101-112. https://doi.org/10.29001/2073-8552-2025-40-4-101-112
JATS XML


.png)

























