Informativeness of markers of systemic inflammation in patients with stable ischemic heart disease: influence of depressive symptoms and restenosis in anamnesis

Objective: the aim of the study was to investigate laboratory markers of inflammation in patients with stable ischemic heart disease, to estimate their interrelation with symptoms of depression. Matherials and methods: 46 men aged from 46 to 75 years hospitalized for the conservative (n = 20) and surgical (n = 26) treatment of ischemic heart disease participated in the study. An evaluation of inflammatory markers (absolute quantity of leukocytes and neutrophils, monocyte/HDL ratio and neutrophil/lymphocyte ratio) was performed. Depressive symptoms were measured using the CES-D scale. Conclusions: symptoms of depression were found in 8 patients (17,37%). 13% of them had symptoms of mild depression, 4,37% - symptoms of severe depression. The monocyte/HDL ratio was significantly higher in patients with ischemic heart disease comparing to healthy individuals. The monocyte/HDL ratio was significantly increased in patients with depressive symptoms, previously implanted stent, restenosis of the coronary stent in anamnesis. Level of leukocytes was higher during the early period after the procedure of percutaneous coronary intervention with stenting and in patients with stent restenosis. Number of neutrophils and the neutrophil/lymphocyte ratio were significantly higher in patients with depression symptoms, during the early period after stent implantation and also with previous restenosis of the stent. Systemic inflammation estimated using routine laboratory tests was significantly higher in both patients with complicated ischemic heart disease, and with symptoms of depressive disorder. Routine laboratory indicators can be informative in assessing inflammation in patients with ischemic heart disease. Symptoms of depression and stent restenosis can be followed by increased inflammatory markers.

1. Bogachevskaya SA, Bogachevskiy AN, Bondar VY. Three-year contribution of functioning of the federal centers of cardiovascular surgery to development of a hi-tech medical care to patients with cardiovascular diseases in Russia. Social aspects of health of the population. 2016;47. (in Russ.) doi: 10.21045/2071-5021-2016-47-1-2

2. Th e report on the state of health of the population and the organization of health care following the results of activity of executive authorities of territorial subjects of the Russian Federation for 2014. Ministry of Health of the Russian Federation. // URL: https://static-0.rosminzdrav.ru/system/ attachments/attaches/000/026/627/original/Doklad_o_ sostojanii_zdorovja_naselenija_2014.pdf?1434640648 (date: 05.03.2018). (in Russ.)

3. Fozilov HG, Alekyan BG. Complications of percutaneous coronary interventions - classifi cation, predictors of development and types of complications. Th e bulletin NTsSSH of A.N. Bakulev of the Russian Academy of Medical Science. Cardiovascular diseases. 2010;11(5):9-15. (in Russ.)

4. Versaci F, Gaspardone A Prevention of restenosis aſt er stenting: the emerging role of infl ammation Francesco Versaci; Achille Gaspardone // Coronary Artery Disease. - 2004. - 15(6). - p. 307-311.

5. Cassese S, Byrne RA, Tada T, Pinieck S, Joner M, et al. Incidence and predictors of restenosis aſter coronary stenting in 10 004 patients with surveillance angiography. Heart. 2014;100(2):153-9. doi: 10.1136/heartjnl-2013-304933

6. Mitra AK, Agrawal DK. In stent restenosis: bane of the stent era. J Clin Pathol. 2006;59(3):232-9. doi: 10.1136/ jcp.2005.025742

7. Gary T, Pichler M, Belaj K, Eller P, Hafner F, et al. Lymphocyte-to monocyte ratio: a novel marker for critical limb ischemia in PAOD patients. Int J Clin Pract. 2014;68(12):1483-7. doi: 10.1111/ijcp.12495

8. Waterhouse DF, Cahill RA, Sheehan F, McCreery C. Prediction of calculated future cardiovascular disease by monocyte count in asymptomatic population. Vasc Health Risk Manag. 2008;4(1):177-87.

9. Nozawa N, Hibi K, Endo M, Sugano T, Ebina T, et al. Association between circulating monocytes and coronary plaque progression in patients with acute myocardial infarction. Circ J. 2010;74(7):1384-91. doi: 10.1253/circj.CJ-09-0779

10. Cetin EH, Cetin MS, Canpolat U, Aydin S, Topaloglu S, et al. Monocyte/HDL-cholesterol ratio predicts the defi nite stent thrombosis aſt er primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Biomark Med. 2015;9(10):967-77. doi: 10.2217/bmm.15.74

11. Ghattas A, Griffi ths HR, Devitt A, Lip GY, Shantsila E. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013;62(17):1541-51. doi: 10.1016/j.jacc.2013.07.043

12. Cetin MS, Ozcan Cetin EH, Kalender E, Aydin S, Topaloglu S, et al. Monocyte to HDL Cholesterol Ratio Predicts Coronary Artery Disease Severity and Future Major Cardiovascular Adverse Events in Acute Coronary Syndrome. Heart Lung Circ. 2016;25(11):1077-1086. doi: 10.1016/j.hlc.2016.02.023

13. Akboga MK, Balci KG, Maden O, Ertem AG, Kirbas O, et al. Usefulness of monocyte to HDL cholesterol ratio to predict high SYNTAX score in patients with stable coronary artery disease. Biomark Med. 2016;10(4):375-83. doi: 10.2217/ bmm-2015-0050

14. Canpolat U, Aytemir K, Yorgun H, Şahiner L, Kaya EB, et al. Th e role of preprocedural monocyte-tohigh-density lipoprotein ratio in prediction of atrial fi brillation recurrence aſt er cryoballoon-based catheter ablation. Europace. 2015;17(12):1807-15. doi: 10.1093/europace/euu291

15. Turak O, Ozcan F, Isleyen A, Tok D, Sokmen E, et al. Usefulness of the neutrophil-to lymphocyte ratio to predict bare-metal stent restenosis. Am J Cardiol. 2012;110(10):1405-10. doi: 10.1016/j.amjcard.2012.07.003.

16. Goldston K, Baillie AJ. Depression and coronary heart disease: A review of the epidemiological evidence, explanatory mechanisms and management approaches. Clin Psychol Rev. 2008;28(2):288-306. DOI: 10.1016/j.cpr.2007.05.005

17. Lett HS, Blumenthal JA, Babyak MA, Sherwood A, Strauman T, et al. Depression as a Risk Factor for Coronary Artery Disease: Evidence, Mechanisms, and Treatment. Psychosomatic Medicine. 2004;66(3):305-315.

18. Charlson FJ, Moran AE, Freedman G, Norman RE, Stapelberg NJ, et al. Th e Contribution of Major Depression to the Global Burden of Ischemic Heart Disease: A Comparative Risk Assessment. BMC Medicine. 2003;11:250. doi: 10.1186/1741-7015-11-250.

19. Hannestad J, DellaGioia N, Bloch M. Th e eff ect of antidepressant medication treatment on serum levels of infl ammatory cytokines: a meta-analysis. Neuropsychopharmacology. 2011;36(12):2452-2459. doi: 10.1038/npp.2011.132

20. Eller T, Vasar V, Shlik J, Maron E. Pro-infl ammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(2):445-50. DOI: 10.1016/j.pnpbp.2007.09.015

21. Cheng T, Dimitrov S, Pruitt C, Hong S. Glucocorticoid mediated regulation of infl ammation in human monocytes is associated with depressive mood and obesity. Psychoneuroendocrinology. 2016;66:195-204. doi: 10.1016/j. psyneuen.2016.01.008

22. Semiz M, Yildirim O, Canan F, Demir S, Hasbek E, et al. Elevated neutrophil/lymphocyte ratio in patients with schizophrenia. PsychiatrDanub. 2014;26(3):220-225.

23. National recommendations about diagnostics and treatment of stable stenocardia (VNOK, 2008.). Cardiovascular therapy and prophylaxis. 2008;7(6). (in Russ.)

24. Vilagut G, Forero CG, Barbaglia G, Alonso J. Screening for Depression in the General Population with the Center for Epidemiologic Studies Depression (CES-D): A Systematic Review with Meta-Analysis. PLoS One. 2016;11(5):e0155431. doi: 10.1371/journal.pone.0155431

25. Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J. 2011;32(1):84-92. doi: 10.1093/eurheartj/ehq371

26. Berg KE, Ljungcrantz I, Andersson L, Bryngelsson C, Hedblad B, et al. Elevated CD14++CD16− Monocytes Predict Cardiovascular Events. Circ Cardiovasc Genet. 2012;5(1):122-31. doi: 10.1161/CIRCGENETICS.111.960385

27. Yi Z, Li Z, Yu S, Yuan C, Hong W, et al. Blood-Based Gene Expression Profi les Models for Classifi cation of Subsyndromal Symptomatic Depression and Major Depressive Disorder. PLoS One. 2012;7(2):e31283. doi: 10.1371/journal. pone.0031283

28. Watanabe SY, Iga J, Ishii K, Numata S, Shimodera S, et al. Biological tests for major depressive disorder that involve leukocyte gene expression assays. J Psychiatr Res. 2015;66-67:1-6. doi: 10.1016/j.jpsychires.2015.03.004

29. Aydin Sunbul E, Sunbul M, Yanartas O, Cengiz F, Bozbay M, et al. Increased Neutrophil/Lymphocyte Ratio in Patients with Depression is Correlated with the Severity of Depression and Cardiovascular Risk Factors. Psychiatry Investig. 2016;13(1):121-6. doi: 10.4306/pi.2016.13.1.121

30. Horne BD, Anderson JL, John JM, Weaver A, Bair TL, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol. 2005;45(10):1638 –1643. DOI: 10.1016/j.jacc.2005.02.054