DOI: https://doi.org/10.24959/cphj.19.1502

The effect of combined therapy with statins and levothyroxine on the lipid profile dynamics in patients with a comorbid course of arterial hypertension, type 2 diabetes mellitus and subclinical hypothyroidism

V. D. Nemtsova, O. M. Ievtushenko, V. V. Chaikovska

Abstract


To date, there are no sufficiently clear recommendations for the management of patients with the TSH level between the upper limit of the control range and 10.0 mIU/L, and with a high cardiovascular risk (CVR).

Aim. to assess the effect of combined therapy with statins and levothyroxine on the state of lipid metabolism and total CVR in patients with comorbid course of arterial hypertension (AH), type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SHT).

Materials and methods. 67 patients aged 44 to 75 years with the stage II AH, T2DM and SHT were included. All patients used statins prior to inclusion in the study. At the TSH level of more than 6.0 μMU/ml levothyroxine was additionally prescribed in individually selected doses from 12.5 to 50 μg/day. Lipid and thyroid metabolism indexes, the concentration of C-reactive protein (CRP) and the tumor necrosis factor-α (TNF-α) were measured by standard methods. The period of observation was 12 months.

Results. Patients with TSH levels of >6.0 μMU/ml, despite statin therapy, have more pronounced dyslipidemia, higher CRP values (p<0.05) and a tendency to increase TNF-α (p>0.05). The additional use of levothyroxine led to a significant decrease in total cholesterol (p=0.011), low-density lipoprotein cholesterol (p=0.025), and a highly significant decrease in CRP and TNF-α (p<0.001).

Conclusions. Combined therapy, including statins and levothyroxine, leads to more significant improvement in the lipid profile than statins without the replacement therapy, a decrease in the signs of systemic inflammation, and, in the aggregate, has a positive effect on the total cardiovascular risk in this category of patients.


Keywords


arterial hypertension; type 2 diabetes mellitus; subclinical hypothyroidism; lipid metabolism; statins; levothyroxine

References


Shestakova, P. P. (2016). Russkii meditcinskii zhurnal (RMZh), 1, 6–8.

Fadeev, V. V. (2013). Klinicheskaia i eksperimentalnaia tireoidologiia, 9(4), 10–14.

Rodondi, N., den Elzen, W. P. J., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., … Thyroid Studies Collaboration, for the. (2010). Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality. JAMA, 304(12), 1365. https://doi.org/10.1001/jama.2010.1361

Budnevskii, A. V., Kravchenko, A. Ia., Drobysheva, E. S., & Feskova, A. A. (2015). Klinicheskaia meditcina, 93(1), 13–17.

Pearce, E. N. (2012). Update in Lipid Alterations in Subclinical Hypothyroidism. The Journal of Clinical Endocrinology & Metabolism, 97(2), 326–333. https://doi.org/10.1210/jc.2011-2532

Tognini, S., Polini, A., Pasqualetti, G., Ursino, S., Caraccio, N., Ferdeghini, M., & Monzani, F. (2012). Age and Gender Substantially Influence the Relationship Between Thyroid Status and the Lipoprotein Profile: Results from a Large Cross-Sectional Study. Thyroid, 22(11), 1096–1103. https://doi.org/10.1089/thy.2012.0013

Hernández-Mijares, A., Jover, A., Bellod, L., Bañuls, C., Solá, E., Veses, S., … Rocha, M. (2013). Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism. Clinical Endocrinology, 78(5), 777–782. https://doi.org/10.1111/cen.12064

Robison, C. D., Bair, T. L., Horne, B. D., McCubrey, R. O., Lappe, D. L., Muhlestein, J. B., & Anderson, J. L. (2014). Hypothyroidism as a risk factor for statin intolerance. Journal of Clinical Lipidology, 8(4), 401–407. https://doi.org/10.1016/j.jacl.2014.05.005

Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013). 2013 ETA Guideline: Management of Subclinical Hypothyroidism. European Thyroid Journal, 2(4), 215–228. https://doi.org/10.1159/000356507

Redford, C., & Vaidya, B. (2017). Subclinical hypothyroidism: Should we treat? Post Reproductive Health, 23(2), 55–62. https://doi.org/10.1177/2053369117705058

Biondi, B., Cappola, A. R., & Cooper, D. S. (2019). Subclinical Hypothyroidism. JAMA, 322(2), 153. https://doi.org/10.1001/jama.2019.9052

Razvi, S., Weaver, J. U., Butler, T. J., & Pearce, S. H. S. (2012). Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality. Archives of Internal Medicine, 172(10). https://doi.org/10.1001/archinternmed.2012.1159

Mancia, G., Fagard, R., Narkiewicz, K., Redón, J., Zanchetti, A., Böhm, M., … Zannad, F. (2013). 2013 ESH/ESC Guidelines for the management of arterial hypertension. Journal of Hypertension, 31(7), 1281–1357. https://doi.org/10.1097/01.hjh.0000431740.32696.cc

Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., … Matthews, D. R. (2014). 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, 38(1), 140–149. https://doi.org/10.2337/dc14-2441

McQuade, C., Skugor, M., Brennan, D. M., Hoar, B., Stevenson, C., & Hoogwerf, B. J. (2011). Hypothyroidism and Moderate Subclinical Hypothyroidism Are Associated with Increased All-Cause Mortality Independent of Coronary Heart Disease Risk Factors: A PreCIS Database Study. Thyroid, 21(8), 837–843. https://doi.org/10.1089/thy.2010.0298

Nemtsova, V., Bilovol, O., Shalimova, A. (2019). 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, 23(2), 98–104. https://doi.org/10.5603/AH.a2019.0006

Stryuk, R. I., Sviridova, M. I., Mkrtumyan, A. M., Golikova, A. A. (2016). Klinicheskaya meditsina, 94, 683–687.

Krysiak, R., Gilowski, W., & Okopien, B. (2015). Different Effects of Atorvastatin on Metabolic and Cardiovascular Risk Factors in Hypercholesterolemic Women with NormalThyroid Function and Subclinical Hypothyroidism. Experimental and Clinical Endocrinology & Diabetes, 123(03), 182–186. https://doi.org/10.1055/s-0034-1396886

Rymar, O. D., Mustafina, S. V., Malyshenko, Iu. A. (2012). Ateroskleroz, 2, 32–38.


GOST Style Citations


1. Шестакова, П. П. Субклинический гипотиреоз – современный взгляд на проблему / П. П. Шестакова // Рус. мед. журн. – 2016. – № 1. – С. 6–8.

 

2. Фадеев, В. В. По материалам клинических рекомендаций по субклиническому гипотиреозу европейской тиреоидной ассоциации 2013 года / В. В. Фадеев // Клиническая и экспериментальная тиреоидол. – 2013. – № 9 (4). – С. 10–14.

 

3. Thyroid studies collaboration: subclinical hypothyroidism and the risk of coronary heart disease and mortality / N. Rodondi, W. P. den Elzen, D. C. Bauer et al. // JAMA. – 2010. – № 304. – P. 1365. https://doi.org/10.1001/jama.2010.1361 

 

4. Субклинический гипотиреоз как одно из причин дислипидемии / А. В. Будневский, А. Я. Кравченко, Е. С. Дробышева, А. А. Феськова // Клиническая медицина. – 2015. – № 1. – С. 13–17.

 

5. Pearce, E. N. Update in lipid alterations in subclinical hypothyroidism / E. N. Pearce // J. Clin. Endocr. – 2012. – № 97 (2). – Р. 326–333. https://doi.org/10.1210/jc.2011-2532 

 

6. Age and gender substantially influence the rela-tionship between thyroid status and the lipo-protein profile : results from a large cross-sectional study /S. Tognini, А. Polini, G. Pasqualetti et al. // Thyroid. – 2012. – № 22. – С. 1096-1103. https://doi.org/10.1089/thy.2012.0013 

 

7. Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism / A. Hernández-Mijares, A. Jover, L. Bellod et al. // Clin. Endocr. (Oxf.). – 2013. – № 78 (5). – P. 777–782. https://doi.org/10.1111/cen.12064 

 

8. Hypothyroidism as a risk factor for statin intolerance / C. D. Robison, T. L. Bair, B. D. Horne et al. // J. Clin. Lipidol. – 2014. – № 8 (4). – Р. 401–407. https://doi.org/10.1016/j.jacl.2014.05.005 

 

9. 13 ETA Guideline : Management of Subclinical Hypothyroidism / S. H. S. Pearce, G. Brabant, L. H. Duntas et al. // Eur. Thyroid J. – 2013. – № 2. – Р. 215–228. https://doi.org/10.1159/000356507 

 

10. Redford, С. Subclinical hypothyroidism : Should we treat? / С. Redford, В. Vaidya // Post Reprod Health. – 2017. – № 23. – С. 55–62. https://doi.org/10.1177/2053369117705058 

 

11. Biondi, В. Subclinical Hypothyroidism : A Review / В. Biondi, A. Cappola, D. Cooper // JAMA. – 2019. – № 322. – С. 153–160. https://doi.org/10.1001/jama.2019.9052 

 

12. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events and mortality / S. Razvi, J. U. Weaver, T. J. Butler, H. S. Pears // Arsh. Intern. Med. – 2012. – № 172. – P. 811–818. https://doi.org/10.1001/archinternmed.2012.1159 

 

13. 13 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) / G. Mancia, R. Fagard, K. Narkiewicz et al. // J. Hypertens. – 2013. – № 31. – Р. 1281–1357. https://doi.org/10.1097/01.hjh.0000431740.32696.cc

 

14. 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 / S. E. Inzucchi, R. M. Bergenstal, J. B. Buse et al. // Diabetes Care. – 2015. – № 38. – Р. 140–149. https://doi.org/10.2337/dc14-2441 

 

15. Hypothyroidism and moderate subclinical hypothyroidism are associated with increased all-cause mortality independent of coronary heart disease risk factors : a PreCIS database study / C. McQuade, M. Skugor, D. M. Brennan et al. // Thyroid. – 2011. – № 21. – Р. 837–843. https://doi.org/10.1089/thy.2010.0298 

 

16. Nemtsova, V. Vascular endothelial growth factor as a marker of endothelial dysfunction in poly- and comorbidity : focus on hypertension, type 2 diabetes mellitus and subclinical hypothyroidism / V. Nemtsova, O. Bilovol, A. Shalimova // Arterial Hypertension. – 2019. – № 23. – Р. 98–104. https://doi.org/10.5603/AH.a2019.0006

 

17. С-реактивный белок как показатель риска сердечно-сосудистых осложнений у больных сахарным диабетом 2-го типа и его коррекция / Р. И. Стрюк, М. И. Свиридова, А. М. Мкртумян, А. А. Голикова // Клин. мед. – 2016. – № 94. – Р. 683–687.

 

18. Krysiak, R. Different effects of atorvastatin on metabolic and cardiovascular risk factors in hypercholesterolemic women with normal thyroid function and subclinical hypothyroidism/ R. Krysiak, W. Gilowski, B. Okopien // Exp. Clin. Endocrinol. Diabetes. – 2015. – № 123. – Р. 182–186. https://doi.org/10.1055/s-0034-1396886 

 

19. Рымар, Д. Назначение статинов у пациентов с гипотиреозом : возможные риски / О. Д. Рымар, С. В. Мустафина, Ю. А. Малышенко // Атеросклероз. – 2012. – № 2. – С. 32–38.





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