State of the coronary arteries and assessment of the role of hormone replacement therapy in patients with coronary heart disease against the background of primary manifest hypothyroidism

Aim To study features of coronary damage and incidence of different types of acute coronary syndrome (ACS) in history associated with primary symptomatic hypothyroidism in patients with ischemic heart disease (IHD) and possible associations of replacement hormonal therapy with lipidogram indexes.
Material and methods This retrospective study included 344 patients with IHD and functional class I-III stable angina (ССS, 1976). Of them 100 patients had primary symptomatic hypothyroidism and 244 had no hypothyroidism. Coronary angiography was performed for all patients included into this study. Routine laboratory, instrumental and clinical indexes were analyzed. Hypothyroidism was confirmed by levels of thyrotropic hormone, free triiodothyronine, and thyroxine. Comparative analysis was performed for the incidence of ACS types in history, types of coronary injury, and laboratory, instrumental and clinical indexes with assessment of potential interrelations. Statistically significant results were reported. Type of data distribution was evaluated with the Kolmogorov-Smirnov test. Quantitative data with normal (Gaussian) distribution were presented as mean (M) and standard deviation (SD). Data with attributes of non-normal distribution were presented as median (Me) with maximum and minimum values (min; max). Statistical significance of differences between means was assessed with the Mann-Whitney test. Logistic regression analysis was used in parallel for evaluating dependence of a quantitative variable on values of two or more quantitative or qualitative variables (factors). Significance level for testing of statistical hypotheses was р<0.05.
Results Incidence of ST segment elevation ACS (STEACS) was significantly higher in IHD patients with hypothyroidism than in the group without hypothyroidism (61.6 and 35.6 %, р=0.03) and also with three-vessel coronary artery disease (60.6 and 30.6 %, р=0.001). In the IHD group with hypothyroidism, levels of total cholesterol, triglycerides, and low- and very low-density lipoproteins were significantly increased compared to the respective values in patients without hypothyroidism (р<0.0001). An inverse correlation was found between lipidogram indexes and L-thyroxine (р<0.0001).
Conclusion The incidence of STEACS associated with primary symptomatic hypothyroidism in history was significantly higher in the patient group with IHD on the background of primary symptomatic hypothyroidism compared to the comparison group. Also, the incidence of three-vessel coronary disease was significantly greater than in the IHD patient group without hypothyroidism. A significant association was found between the replacement hormonal therapy and the best lipidogram indexes. The authors suggested that the key factor for prevention of adverse cardiovascular events in IHD with hypothyroidism is achieving control of clinical manifestations of hypothyroidism with replacement hormonal therapy.

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London, England). 2015;385(9963):117–71. DOI: 10.1016/S0140-6736(14)61682-2

2. Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. European Heart Journal. 2016;37(42):3232–45. DOI: 10.1093/eurheartj/ehw334

3. Hanlon P, Hannigan L, Rodriguez-Perez J, Fischbacher C, Welton NJ, Dias S et al. Representation of people with comorbidity and multimorbidity in clinical trials of novel drug therapies: an individual-level participant data analysis. BMC Medicine. 2019;17(1):201–2. DOI: 10.1186/s12916-019-1427-1

4. Nwaneri C, Cooper H, Bowen-Jones D. Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis. The British Journal of Diabetes & Vascular Disease. 2013;13(4):192–207. DOI: 10.1177/1474651413495703

5. Sumin A.N., Korok E.V., Shcheglova A.V., Barbarash O.L. Gender features of comorbidity in patients with coronary artery disease. Therapeutic Archive. 2018;90(4):42–9. DOI: 10.26442/terarkh201890442-49

6. Ankudinov A.S., Kalyagin A.N. Immunomodulating cytokines in chronic heart failure associated with knee osteoarthritis. Siberian Medical Journal (Irkutsk). 2015;137(6):109–12.

7. Glezeva N, Baugh JA. Role of inflammation in the pathogenesis of heart failure with preserved ejection fraction and its potential as a therapeutic target. Heart Failure Reviews. 2014;19(5):681–94. DOI: 10.1007/s10741-013-9405-8

8. Dedov I.I., Shestakova M.V., Vikulova O.K. Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry. Diabetes mellitus. 2017;20(1):13–41. DOI: 10.14341/ DM8664

9. Fadeev V.V. The use of l-t4 + l-t3 in the treatment of hypothyroidism: guidelines of the European Thyroid Association. Clinical and experimental thyroidology. 2012;8(2):14–8.

10. Panchenkova L.A., Yurkova T.E., Schelkovnikova M.O., Martynov A.I. Special features of cardiovascular system in patients with coronary heart disease with subclinical thyroid dysfunction. Russian Journal of Cardiology. 2003;8(6):5–9.

11. Dey A, Kanneganti V, Das D. A study of the cardiac risk factors emerging out of subclinical hypothyroidism. Journal of Family Medicine and Primary Care. 2019;8(7):2439–44. DOI: 10.4103/jfmpc.jfmpc_348_19

12. Saif A, Mousa S, Assem M, Tharwat N, Abdelhamid A. Endothelial dysfunction and the risk of atherosclerosis in overt and subclinical hypothyroidism. Endocrine Connections. 2018;7(10):1075–80. DOI: 10.1530/EC-18-0194

13. Kong SH, Yoon JW, Kim SY, Oh TJ, Park K-H, Choh JH et al. Subclinical Hypothyroidism and Coronary Revascularization After Coronary Artery Bypass Grafting. The American Journal of Cardiology. 2018;122(11):1862–70. DOI: 10.1016/j.amjcard.2018.08.029

14. Moon S, Kim MJ, Yu JM, Yoo HJ, Park YJ. Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. Thyroid. 2018;28(9):1101–10. DOI: 10.1089/thy.2017.0414

15. Gong N, Gao C, Chen X, Fang Y, Tian L. Endothelial Function in Patients with Subclinical Hypothyroidism: A Meta-Analysis. Hormone and Metabolic Research. 2019;51(11):691–702. DOI: 10.1055/a1018-9564

16. Hashemi MM, Kosari E, Mansourian AR, Marjani A. Serum levels of nitrite/nitrate, lipid profile, and Fasting Plasma Glucose and their associations in subclinical hypothyroid women before and after a two month treatment by levothyroxine. Romanian Journal of Internal Medicine. 2017;55(4):205–11. DOI: 10.1515/rjim-2017-0022

17. Fernandez-Ruocco J, Gallego M, Rodriguez-de-Yurre A, Zayas-Arrabal J, Echeazarra L, Alquiza A et al. High Thyrotropin Is Critical for Cardiac Electrical Remodeling and Arrhythmia Vulnerability in Hypothyroidism. Thyroid. 2019;29(7):934–45. DOI: 10.1089/thy.2018.0709

18. Rajão KMAB, Ribeiro ALP, Passos VMA, Benseñor IJM, Vidigal PG, Camacho CP et al. Subclinical Thyroid Dysfunction was not Associated with Cardiac Arrhythmias in a Cross-Sectional Analysis of the ELSA-Brasil Study. Arquivos Brasileiros de Cardiologia. 2019;12(6):758–66. DOI: 10.5935/abc.20190037

19. de Miranda EJFP, Bittencourt MS, Staniak HL, Sharovsky R, Pereira AC, Foppa M et al. Thyrotropin and free thyroxine levels and coronary artery disease: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Brazilian Journal of Medical and Biological Research. 2018;51(5):e7196. DOI: 10.1590/1414-431x20177196

20. Montalescot G, Sechtem W, Achenbach S, Andreotti F, Arden C, Budaj A et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. European Heart Journal. 2013;34(38):2949–3003. DOI: 10.1093/eurheartj/eht296

21. Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L et al. American association of clinical endocrinologists, American college of endocrinology, and association medical endocrinology medical guidelines for clinical practice for the diagnosis and management of thyroid nodules – 2016 update. Endocrine Practice. 2016;22(Suppl 1):1–60. DOI: 10.4158/EP161208.GL

22. Sara JD, Zhang M, Gharib H, Lerman LO, Lerman A. Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women. Journal of the American Heart Association. 2015;4(8):e002225. DOI: 10.1161/JAHA.115.002225

23. Saric MS, Jurasic M-J, Sovic S, Kranjcec B, Glivetic T, Demarin V. Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C). Romanian Journal of Internal Medicine. 2017;55(3):159–66. DOI: 10.1515/rjim-2017-0015

24. Cai X-Q, Tian F, Han T-W, Shan D-K, Liu Y, Yin W-J et al. Subclinical hypothyroidism is associated with lipid-rich plaques in patients with coronary artery disease as assessed by optical coherence tomography. Journal of Geriatric Cardiology. 2018;15(8):534–9. DOI: 10.11909/j.issn.1671-5411.2018.08.007