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

Authors

DOI:

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

Keywords:

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

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.

Author Biographies

V. D. Nemtsova, Kharkiv National Medical University

Candidate of Medicine (Ph.D), associate professor of the Clinical Pharmacology and Internal Medicine Department

O. M. Ievtushenko, National University of Pharmacy

Doctor of Pharmacy (Dr. habil), professor of the Department of Pharmaceutical Marketing and Management

V. V. Chaikovska, National Medical Academy of Postgraduate Education named after P. L. Shupik

Doctor of Medicine (Dr. habil), professor of the Department of Palliative and Hospice Medicine, member of the Expert Council on Palliative Medicine and Geriatrics of the Ministry of Health of Ukraine

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.

Published

2019-08-30

Issue

Section

Clinical Pharmacology and Pharmacotherapy