The purpose of the study was to evaluate the effect of levothyroxine supplementation on vascular endothelium status and markers of chronic systemic inflammation in patients with combined course of arterial hypertension, type 2 diabetes mellitus, and subclinical hypothyroidism. Material and methods. The study included 32 patients (mean age 59.3±3.5 years) with arterial hypertension stage II in combination with type 2 diabetes mellitus and subclinical hypothyroidism. The inclusion criterion was the presence of a TSH level of more than 6.0 mIU / L in the screening period. The control group consisted of 30 representatives by age and gender, without cardiovascular disease and endocrinopathies. Levothyroxine was administered in individually selected doses of 12.5 to 50 mg/day with gradual dose titration (21 day titration step) until euthyroidism was reached. The period of observation was 1 year, 28 (87.5 %) patients completed the study. Plasma levels of vasculoendothelial growth factor (VEGF–A), C–reactive protein, tumor necrosis factor–α (TNF–α) were checked by ELISA. The number of desquamating circulating endothelial cells in the blood was determined by the method of Hladovec J. in the modification of Rajec J. et al. using phase contrast microscopy. Statistical processing of data was performed with the computer program SPSS 21.0. Results and discussion. A comparative analysis revealed signs of chronic systemic inflammation, endothelial dysfunction on the background of decreased thyroid function in patients with arterial hypertension, type 2 diabetes mellitus and subclinical hypothyroidism compared with the control group. Correlation analysis revealed a positive correlation between VEGF–A and TSH levels (r=0.421, p=0.001). Improvement of the thyroid function on the background of treatment with levothyroxine was accompanied by a significant decrease in the level of VEGF–A (before treatment 585,67±35,08 pg / ml, after treatment – 462,58±32,18 pg / ml, p<0,001, respectively), not a significant decrease in the desquamating circulating endothelial cells count (before treatment it was 10.28±0.61 (cell./100 μl), after treatment it was 10.16±0.59 (cell./100 μl), p = 0.083, respectively), a slight but significant decrease of C–reactive protein (p<0.001) and TNF–α (p <0.001). Post–treatment correlation analysis revealed a positive relationship between free T3 and VEGF–A levels (r = 0.481, p = 0.015), and a negative relationship between desquamating circulating endothelial cells and free T4 levels (r = 0.457, p = 0.022). Conclusion. The use of levothyroxine in the complex treatment of patients with combined course of arterial hypertension, type 2 diabetes mellitus and subclinical hypothyroidism was accompanied by an improvement in the functional state of the endothelium, which together with decreased markers of chronic systemic inflammation improved the prognosis for this cohort of patients.

Keywords: arterial hypertension, type 2 diabetes mellitus, subclinical hypothyroidism, endothelial dysfunction, levothyroxine

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1. Kolesnikova O, Potapenko A. Effect of the cardiometabolic risk factors on vascular aging in patients with non–alcoholic fatty liver disease concomitant with subclinical hypothyroidism. Georgian medical news. 2017; 9(270): 69–75.
2. Colpani V, Baena CP, Jaspers L, van Dijk GM, Farajzadegan Z, Dhana K et al. Lifestyle factors, cardiovascular disease and all–cause mortality in middle–aged and elderly women: a systematic review and meta–analysis. Eur J Epidemiol. 2018 Sep; 33(9): 831–45. PMID: 29524110. https://doi.org/10.1007/s10654-018-0374-z
3. Roytman AP. Laboratornye markery serdechno–sosudystykh zabolevanyy. znachenye v otsenke effektyvnosty terapyy [Laboratory markers of cardiovascular disease. importance in evaluating the effectiveness of therapy]. Abstr. Dr. Sci. (Med.). M; 2012. 276 p. [Russian]
4. Smyrnova EN, Shulkyna SG, Smyrnova EN, Shulkyna SG, Shchekotov VV, Antypova AA. Vaskuloendotelyalnyy faktor rosta kak marker endotelyalnoy dysfunktsyy y rannego povrezhdenyya pochek u bolnykh metabolycheskym syndromom. Sovremennye problemy nauky y obrazovanyya [Vasculoendothelial growth factor as a marker of endothelial dysfunction and early kidney damage in patients with metabolic syndrome]. [Internet]. 2015; 5. Available from: https://www.science–education.ru/ru/article/view?id=21800 [Russian]
5. Zakharova NB, Durnov DA, Mykhaylov VYu, Ponukalyn AN, Nykytyna VV, Zankyna OV, y dr. Dyagnostycheskoe znachenye yssledovanyya faktora rosta endotelyya sosudov v syvorotke krovy [The diagnostic value of the study of vascular endothelial growth factor in blood serum]. Fundamentalnye yssledovanyya. 2011; 11(1): 215–20. [Russian]
6. Feoktystova BC, Vavylova TB, Syrotkyna OV, Boldueva SA, Gaykovaya LB, Leonova YA, y dr. Novyy podkhod k otsenke dysfunktsyy endotelyya: opredelenye kolychestva tsyrkulyruyushchykh endotelyalnykh kletok metodom protochnoy tsytometryy [A new approach to assessing endothelial dysfunction: determining the number of circulating endothelial cells by flow cytometry]. Klynycheskaya laboratornaya dyagnostyka. 2015; 4: 23–39. [Russian]
7. Nemtsova V, Bilovol O, Shalimova A.Vascular endothelial growth factor as a marker of endothelial dysfunction in poly– and comorbidity: focus on hypertension, type 2 diabetes mellitus and subclinical hypothyroidism. Arterial Hypertension 2019; 23(2): 98–104. https://doi.org/10.20517/2574-1209.2018.48
8. Bielecka–Dabrowa A, Godoy B, Suzuki T, Banach M, von Haehling S. Subclinical hypothyroidism and the development of heart failure: an overview of risk and effects on cardiac function. Clin Res Cardiol. 2019 Mar; 108(3): 225–33. PMID: 30091084. https://doi.org/10.1007/s00392-018-1340-1
9. Floriani C, Gencer B, Collet TH, Rodondi N. Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update. Eur Heart J. 2018 Feb 14; 39(7): 503–7. PMID: 28329380. https://doi.org/10.1093/eurheartj/ehx050
10. Niknam N, Khalili N, Khosravi E, Nourbakhsh M. Endothelial dysfunction in patients with subclinical hypothyroidism and the effects of treatment with levothyroxine. Adv Biomed Res. 2016; 5: 38. PMID: 27099851. PMCID: PMC4815523. https://doi.org/10.4103/2277-9175.178783
11. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, 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 of Hypertension. 2013; 31(7): 1281–357. PMID: 23817082. https://doi.org/10.1097/01.hjh.0000431740.32696.cc
12. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient–Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 015 Jan; 38(1): 140–9. PMID: 25538310. https://doi.org/10.2337/dc14-2441
13. Pearce SH, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. European Thyroid Journal.2013; 2: 215–28. PMID: 24783053. PMCID: PMC3923601. https://doi.org/10.1159/000356507
14. Gong N, Gao C, Chen X, Wang Y, Tian L. Adipokine expression and endothelial function in subclinical hypothyroidism rats. Endocr Connect. 2018 Feb; 7(2): 295–304. PMID: 29440225. PMCID: PMC5811986. https://doi.org/10.1530/EC-18-0007
15. Samytyn VV. Kompleksnaya otsenka funktsyy endotelyya pry subklynycheskom gypotyreoze [Comprehensive assessment of endothelial function in subclinical hypothyroidism]. Abstr. PhDr. (Med.). Samara; 2010. 155 p. [Russian]
16. Dolbyn YV, Ekymovskykh AYu. Vlyyanye zamestytelnoy terapyy levotyroksynom na markery systemnogo vospalenyya u bolnykh s pervychnym subklynycheskym gypotyreozom y yshemycheskoy boleznyu serdtsa. Vestnyk sovremennoy klynycheskoy medytsyny. 2017; 10(2): 18–24. [Russian]