Issues associated with the formation of cardiovascular risk in patients with subclinical hypothyroidism (SH) in combination with non-alcoholic hepatic steatosis (NAHS) remain the subject of discussion. This topic is popular because of the increasing number of SH in the population, active detection and monitoring of each patient. It is caused by the fact that the presence of SH contributes to the early formation of the atherosclerotic process, especially when the patient also has NAHS. We are studying a variety of drugs in order to prevent the development of vascular changes in patients with SH in combination with NASH. The effectiveness of levothyroxine therapy was shown by the achievement compensation of the thyroid function, rosuvastatin – to achieve target lipid levels, cytoprotectors – to restore the function of hepatocytes. However, until now, there are no studies that w include the effectiveness of the complex effect on the various mechanisms of cardiovascular disease in patients with SH in combination with NAHS. Therefore, the aim of our study is evaluation of cardiometabolic indicators by using complex therapy in patients with SH in combination with NAHS. The study included 67 patients with SH in combination with NAHS. Patients were divided into 3 groups depending on the therapeutic options: Group 1 (n = 20) cjmprised patients, who received levothyroxine substitution therapy. For all patients, who were included in the study, the dose of levothyroxine was individually selected in the range of 25-100 μg / day, depending on the level of TSH. Group 2 (n = 18) received levothyroxine and rosuvastatin 10 mg / day. Group 3 consisted of 19 individuals who received rosuvastatin 10 mg / day in combination with cytoprotector Betargin (arginine + betaine) 30 ml / day with the addition of hormonal substitution therapy in oral solution twice in the 3 months in the observation period. Duration of the study was 12 months. The dose of levothyroxine was based on the level of TSH, which was determined every 2 months in all patients. As a result of the study, a significant decrease in T4 (p <0.05) was noted in patients of the 2nd and 1st groups, as well as 3rd and 1st groups, which evidences their euthyroid status. Indicators of total cholesterol significantly differed from the group before treatment in groups 2 and 3, who received statins as a part of the complex therapy, p <0.05. At the same time, a decrease of TG, LDL cholesterol, LDL cholesterol and increase of HDL cholesterol were observed only in patients of the 3rd group, p <0,05. The improvement in the lipid profile of group 3 is probably due to the combined effect of the therapy by levothyroxine, rosuvastatin and betargin, which confirms the cardiometabolic effects of this option. In the dynamics of the therapy, the parameters of liver functional tests, especially ALT and GGTP, have significant changes in all groups, despite the presence of statins in the complex therapy. Comparison of ALT and GGPT in groups 2 (3) and 1 showed more significant changes in favor of normalization in patients, who received complex therapy compared to monotherapy levothyroxine. Evaluation of the effect of therapy with levothyroxine in combination with rosuvastatin demonstrated a significant decrease in the level of circulating desquamated epithelial cells (CDEC) and CRP in comparison with patients, who received monotherapy with levothyroxine. Significant changes occurred in "vascular" factors considered to be the result of a considerable shift under the influence of protective therapy of group 3 compared with the 1st and 2nd groups. In general, indicators which characterize changes in the function of endothelium in SH patients in combination with NAHS, such as CDEC, VEGF-A, and CRP, as independent predictors of the risk of developing cardiovascular disease (CVD) and complications, have significant changes therefore confirming the effectiveness of the complex therapy.

Keywords: subclinical hypothyroidism, non-alcoholic hepatic steatosis, cardiometabolic indices, complex therapy, dynamics of treatment

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1. Chung GE, Kim D, Kim W, Yim JY, Park MJ, Kim YJ., et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol. 2012; 57 (1): 150-6. https://doi.org/10.1016/j.jhep.2012.02.027.
2. Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007; 297 (120): 1344-53.
3. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of Hepatology. 2016; 64 (6): 1388-402. https://doi.org/10.1016/j.jhep.2015.11.004.
4. Köroglu BK, Bagci Ö, Ersoy IH, Aksu O, Balkarli A, Alanoglu E, Tamer MN. Effects of levothyroxine treatment on cardiovascular risk profile and carotida intima media thickness in patients with subclinical hypothyroidism. Acta Endocrinologica (Buc). 2012; 8 (3): 433-42. https://doi.org/10.4183/aeb.2012.433.
5. Lee SW, Cho KI, Kim HS, Heo JH, Cha TJ. The impact of subclinical hypothyroidism or thyroid autoimmunity on coronary vasospasm in patients without associated cardiovascular risk factors. Korean Circ J. 2015; 45 (2): 125–30. https://doi.org/10.4070/kcj.2015.45.2.125.
6. McTaggart F. Comparative pharmacology of rosuvastatin. Atherosclerosis. 2003; Suppl 4: 9-14.
7. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L -thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007; 92 (5): 1715–23.
8. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events and mortality. Arch Intern Med. 2012; 172 (10): 811–8. https://doi.org/10.1001/archinternmed.2012.1159.
9. Teerlink T, Luo Z, Palm F, Wilcox CS. Celular ADMA: regulation and action. Pharmacol Res. 2009; 60 (6): 448-60. https://doi.org/10.1016/j.phrs.2009.08.002.
10. Wadhera RK, Steen DL, Khan I, Giugliano RP, Foody JM. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol. 2016; 10 (3): 472-89. https://doi.org/10.1016/j.jacl.2015.11.010