Association of tumor necrosis factor-alpha and interleukin-10 levels with ultrasound characteristics of atherosclerotic plaques in patients with essential hypertension

Aim. To study the association  of ultrasound characteristics of carotid atherosclerotic  plaques  (ASPs) with the concentration  of tumor necrosis factor-alpha  (TNFα) and interleukin-10 (IL-10) in patients  with essential hypertension.

Material and methods. The study included 117 patients  (men, 75; women, 42) with essential hypertension aged 40 to 75 years (mean age, 55,8±7,5 years). All patients  underwent anthropometric  measurements (height, weight, body mass index, waist circumference),  assessment of blood pressure  and heart rate, blood tests (levels of glucose, creatinine with the calculation of glomerular filtration rate using CKD-EPI equation, lipid profile), duplex ultrasound of the carotid arteries.  Also, the blood concentration  of TNFα and IL-10 by the enzyme-linked immunosorbent assay using CYTOKIN-STIMUL-BEST (Novosibirsk,Russia) kit was determined.

Results.  According to the  results  of carotid  duplex ultrasound,  3 groups of patients  were identified. Group 1 included 48 patients  with homogeneous hyperechoic ASPs; group 2 — 56 patients with dominant hyperechoic  ASPs (>50% of areas);  group 3 — 13 patients  with anechoic, unstable,  low-density ASPs. TNFα concentration  in group 3 patients, amounting to 10,51±2.23 pg/ml, was significantly higher than in patients of group 1 (7,26±0,64 pg/ml (p<0,001)) and group 2 (8,93±0,98 pg/ml (p<0,001)).  Similar results were obtained for IL-10. The logistic regression  showed that the TNFα concentration  is an independent  factor associated with unstable  ASsP (relative risk, 2,72; 95% confidence interval 1,44-5,15  (p<0,02)). It was also revealed that TNFα >10 pg/ml increased the risk of ASP instability by ~8 times.

Conclusion.  An increase  in TNFα >10 pg/ml with a high specificity (95%) was associated with vulnerable unstable carotid ASPs.

1. Falk E, Fuster V. Angina pectoris and disease progression. Circulation. 1995;92(8):2033-5. doi:10.1161/01.CIR.92.8.2033.

2. Schwartz SM, Galis ZS, Rosenfeld ME, Falk E. Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol. 2007;27(4):705-13. doi:10.1161/01.ATV.0000261709.34878.20.

3. Buko IV, Polonetsky IZ, Moiseenok AG. Erythrocyte glutatione and parameters of oxidative stressand inflammation in acute coronary syndrome. “Arterial’naya Gipertenziya” (“Arterial Hypertension”). 2014;20(3):172-81. (In Russ.) doi:10.18705/1607-419X-2014-20-3-172-181.

4. Poredos P, Spirkoska A, Lezaic L, et al. Patients with an Inflamed Atherosclerotic Plaque have Increased Levels of Circulating Inflammatory Markers. J Atheroscler Thromb. 2017;24(1):39-46. doi:10.5551/jat.34884.

5. Nighoghossian N, Derex L, Douek P. The vulnerable carotid artery plaque: current imaging methods and new perspectives. Stroke. 2005;36(12):2764-72. doi:10.1161/01.STR.0000190895.51934.43.

6. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.

7. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-357. doi:10.1097/01.hjh.0000431740.32696.cc.

8. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists’ Collaborative Group. Lancet. 1991;337(8752):1235-43.

9. Gray-Weale AC, Graham JC, Burnett JR, et al. Carotid artery atheroma: comparison of preoperative B-mode ultrasound appearance with carotid endarterectomy specimen pathology. J Cardiovasc Surg (Torino). 1988;29(6):676-81.

10. Schulz R, Post H, Sakka S, et al. Intraischemic preconditioning. Increased tolerance to sustained low-flow ischemia by a brief episode of no-flow ischemia without intermittent reperfusion. Circ Res. 1995;76(6):942-50. doi: 10.1161/01.RES.76.6.942.

11. Esmon CT. Interactions between the innate immune and blood coagulation systems. Trends Immunol. 2004;25(10):536-42. doi:10.1016/j.it.2004.08.003.

12. Caligiuri G, Stahl D, Kaveri S, et al. Autoreactive antibody repertoire is perturbed in atherosclerotic patients. Lab Invest. 2003;83(7):939-47. doi:10.1097/01.LAB.0000077010.90550.FF.

13. Anguera I, Miranda-Guardiola F, Bosch X, et al. Elevation of serum levels of the anti-inflammatory cytokine interleukin-10 and decreased risk of coronary events in patients with unstable angina. Am Heart J. 2002;144(5):811-7. doi:10.1067/mhj.2002.124831.

14. George J, Schwartzenberg S, Medvedovsky D, et al. Regulatory T cells and IL-10 levels are reduced in patients with vulnerable coronary plaques. Atherosclerosis. 2012;222(2):519-23. doi:10.1016/j.atherosclerosis.2012.03.016.

15. Halvorsen B, Waehre T, Scholz H, et al. Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms. J Lipid Res. 2005;46(2):211-9. doi:10.1194/jlr.M400324-JLR200.

16. Ragino YuI, Chernjavski AM, Polonskaya YaV, et al. Inflammatoru-destructive biomarkers of atherosclerotic plaques instability: study of arterial wall and blood. Kardiologiia. 2012;5(52):37-41. (In Russ.)

17. Polonskaya YaV, Chernyavski AM, Volkov AM, et al. Correlations of inflammatory and destructive biomarkers in blood and in vascular wall in men with coronary atherosclerosis. Bulletin of SB of the RAMS. 2011;5:25-31. (In Russ.)

18. Ragino YuI, Chernjavski AM, Tsimbal SYu, et al. Relationship of blood levels of inflammatory and destructive biomarkers in coronary atherosclerosis with long-term results of surgical revascularization. Bulletin of Experimental Biology and Medicine. 2013;155(3):314-7. (In Russ.) doi:10.1007/s10517-013-2142-0.

19. Puz P, Lasek-Bal A, Ziaja D, et al. Inflammatory markers in patients with internal carotid artery stenosis. Arch Med Sci. 2013;9(2):254-60. doi:10.5114/aoms.2013.34533.

20. Puz P, Lasek-Bal A. Repeated measurements of serum concentrations of TNF-alpha, interleukin-6 and interleukin-10 in the evaluation of internal carotid artery stenosis pro- gression. Atherosclerosis. 2017;263:97-103. doi:10.1016/j.atherosclerosis.2017.06.008.