CC BY
17
УДК 616.441-008.64:616.1-02 DOI: 10.22141/2224-0721.13.7.2017.115749
O.Yu. Horodynska
Higher State Education Institution of Ukraine "Ukrainian Medical Stomatological AcademyPoltava, Ukraine
Syndrome of hypothyroidism as a factor of cardiovascular pathology development (literature review)
For cite: Mezhdunarodnyi Endokrinologicheskii Zhurnal. 2017;13(7):503-505. doi: 10.22141/2224-0721.13.7.2017.115749
Abstract. The article presents pathogenetic data on the development of cardiovascular pathology in reduced thyroid function. Нypothyroidism is associated with an increased risk of coronary heart disease, myocardial infarction, chronic heart failure and cardiovascular mortality, regardless of gender, age and previous cardiovascular disease. This leads to the search for additional influence on the pathogenetic mechanisms of hypothyroidism in order to effectively treat these threatening manifestations and consequences of the disease. Keywords: hypothyroidism; coronary heart disease; review
C2> ■ FJ ® Огляд лператури
/Literature Review/
International journal of endocrinology
Introduction
In modern medical science the thyroid dysfunction is one of the risk factors for cardiovascular disease. This fact is unpredictably underestimated, unfortunately [1].
Many studies, devoted to the mechanisms of the influence of reduced function of the thyroid gland on the cardiovascular system, have been organized. Slight disorders of the thyroid function may be accompanied by an increasing of cardiometabolic risk [2, 3]. It has been shown that hypothyroidism has a significant impact on the formation and development of cardiovascular diseases even at the early (subclinical) phase. The results of large-scale studies show that subclinical hypothyroi-dism is associated with an increased risk of coronary heart disease, myocardial infarction, chronic heart failure and cardiovascular mortality, regardless of gender, age and previous cardiovascular disease [4]. Metabolic relationships are found between hypothyroidism and the risk factors of cardiovascular diseases, that accompany by obesity, arterial hypertension, lipid and carbohydrate metabolism disorder [5].
The increasing of the coronary atherosclerosis prevalence in patients with hypothyroidism compared to patients with euthyroidism has led to the emergence of studies that examine the thyroid hormones effect on the synthesis of lipids. The hypothyroidism was detected in 30—45 % of cases in patients with chronic forms of
coronary heart disease [6]. Secondary dyslipidemia is a pathogenetic factor that binds hypothyroidism and the development of atherosclerosis [7].
According to the Colorado population study, which included 25 862 patients, the prevalence of hypothyroidism was 4—21 % for women and 3—16 % for men, depending on their age. The severity of hypercholesterolemia was directly related to the increased levels of the TSH. The medium levels of total cholesterol and low-density lipoprotein cholesterol were significantly higher in patients with TSH 5.1—10 mlU/l than in patients with euthyroidism [8]. The low levels of thyroid hormones slow down the decomposition of lipids however the synthesis of lipids is preserved, which leading to hyperlipi-demia [9].
Hypothyroidism reduces expression of the SREBP-gene, which regulates the absorption and synthesis of the cholesterol. The authors demonstrate that this gene is regulated by the thyroid hormones [10]. The thyroid hormones induce of the 3-hydroxy-3-methylglutaric-coen-zyme-A-reductase and are involved in the process of the first stage of cholesterol synthesis. Triiodothyronine also regulates the activity of the receptors of low density lipoprotein and controls the activity of the genes responsible for them [11], and protects low-density lipoprotein from oxidation [12]. It is responsible for reducing the amount and sensitivity of the receptors of low density lipoprotein
© «International Journal of Endocrinology», 2017 © «М1жнародний ендокринолопчний журнал», 2017
© Publisher Zaslavsky O.Yu., 2017 © Видавець Заславський О.Ю., 2017
For correspondence: O. Horodynska, Higher State Education Institution of Ukraine "Ukrainian Medical Stomatological Academy", Shevchenko st., 23, Poltava, 36011, Ukraine; е-mail: [email protected]
Для кореспонденцп: Городинська О.Ю., Вищий державний навчальний заклад Украши «Украшська медична стоматолопчна академ1я», вул. Шевченка, 34, м. Полтава, 36011, Укра'на; е-mail: [email protected]
OrAflA ArrepaiypM /Literature Review/
in the liver; impairs renal glomerular function (decreased glomerulars filtration) and slows down the clearance of low density lipoprotein [13].
Thyroid hormones stimulate the conversion of the cholesterol to bile acids. The T3 regulates the activity of the main enzyme in the synthesis of bile acids — cholesterol-7a-hydroxylase, which in conditions of hypothyroidism, accelerates the disintegration of cholesterol in the liver and increases its level in the blood [14].
The hypothyroidism leads to the decrease of the activity of cholesterol-ester transport protein, which is a primary factor of the metabolism of high-density lipoprotein and hepatic lipase, providing 30 % of the reverse transport of cholesterol [15].
At the stage of the subclinical hypothyroidism increased concentrations of lipoprotein-associated phos-pholipase A2 (Lp-PLA2), known as marker of coronary heart disease [16], and decreased activity of Lp-PLA2 HDL, which is associated with anti-atherogenic efects of the high-density lipoprotein observed. In addition, T3 regulates apolipoprotein A, which plays a major role in controlling triglyceride levels [17].
Thus, insufficiency of the thyroid hormones leads to the hypercholesterolemia, and it is a characteristic symptom of the hypothyroidism. Than higher is the level of the TSH, the higher is the content of cholesterol [18].
Hormones of the thyroid gland are vasodilators, that influence on the smooth muscle of vessels and are a nonlipid risk factor of cardiovascular disease [19]. The hy-pothyroidism leads to an increased peripheral vascular resistance, which leads to vasoconstriction of the vessels, promotes the development of hypertension. In addition, thyroid hormones are stimulating the activity of the 5-deodynediase of the second type in smooth muscle cells, which provide the conversion of T4 to active T3 and contribute to the relaxation of the blood vessels [20]. Also with hypothyroidism, products of protein metabolism (glycosaminoglycans, derivatives of protein, glucuronic acid and chondroitin sulfuric acids) accumulates in the interstitium, which causes the mucinous edema and vascular dysfunction [14].
The deficiency of NO in hypothyroidism leads to the development of arterial hypertension. Together with the endothelial dysfunction it leads to the stimulation of the proliferation of the vascular cell wall, what promotes the development of fibrosis and changes vascular adaptation mechanisms, increases the risk of atherosclerosis [6, 9, 13].
Another factor in hypothyroidism, which contributes into the increased cardiovascular risk — is a disorder in the hemostasis: microtrombus slab, increased viscosity and density of blood, which changes the microcirculation, promotes perivascular edema, the emergence of the blood resistance and increased blood pressure [4, 8].
It was established that the decrease in the concentration of thyroid hormones leads to changes in metabolism of the energy and neurotransmitter, forms a syndrome of secondary immunological deficiency, promotes the activation of lipid peroxidation processes and the appearance of hypercholesterolemia [3, 17].
_i El
It has been proved that in patients with autoimmune thyroiditis and hypothyroidism, the presence of systemic inflammation of the low activity causes the development of the endothelial dysfunction [7]. The thickness of the intima-medial complex of carotid arteries in women with obesity and autoimmune thyroiditis, which confirms the important participation of hypothyroidism in the progression of atherosclerotic vascular damage, is demonstrated [20].
In patients with hypothyroidism an increased thickness of intima-media of carotid arteries, in comparison with euthyroid individuals, was found. And the degree of thickening is closely correlated with the low-density lipoprotein and TSH [32, 39].
Conclusions
Thus, the influence of the hypothyroidism on the cardiovascular system is carried out by mechanisms such as atherogenic dyslipidemia, endodontic dysfunction, activation of the system of hemocoagulation, the increase of peripheral vascular support, the increase of the tone of the sympathoadrenal system, the decrease vasodilatational properties of blood vessels. This leads to the search for additional influence on the pathogenetic mechanisms of the hypothyroidism in order to effectively treat these threatening manifestations and consequences of the disease.
Conflicts of interests. Authors declare the absence of any conflicts of interests that might be construed to influence the results or interpretation of their manuscript.
References
1. Abramova NO. Peculiarities of lipid metabolism inindi-viduals with metabolic syndrome against a background of thyroid homeostasis violations. Klinichna ta eksperymentalna patologiya. 2013;1(43):11-14. (in Ukrainian).
2. Blankova ZN, Ageev FT, Seredenina EM, Rjabceva OJu, Svirida ON, Irtuganov NShh. Hypothyroidism and cardiovascular diseases. Russkij Medicinskij Zhurnal. 2014;22(13):980-987. (in Russian).
3. Zubkova ST, Bulat OV, Mykhajlenko OJu. Estimation of endothelial function state in patients with hypothyroidism. En-dokrynologija. 2011;16:49-54. (in Ukrainian).
4. Kihtiak OP, Skrypnyk NV, Pasiechko NV. Features of carbohydrate and lipid metabolism in patients with hypothyroidism. Visnik naukovih doslidzen. 2012;2(67):27-28. (in Ukrainian).
5. Kravchun HA, Iu.I. Karachentsev Iul, Goncharova OA, et al. Dislipidemii pri endokrinnykh zabolevaniiakh [Dyslipidemia at endocrine diseases]. Kharkiv; 2008. 224p. (in Russian).
6. Melehovec'' OK, Demihova NV. A value of intima-media complex for the estimation of vascular remodeling in patients with hypothyroidism. Zaporozhskii meditsinskii zhurnal. 2012;3(72):100-102. (in Ukrainian).
7. Mitchenko OI, Logvinenko AO, Romanov VYu. The optimisation of lipid and carbohydrate exchange correction in patients with metabolic syndrome and thyroid dysfunction. Ukrai'ns'kyj KardiologichnyjZhurnal. 2010;1:73-80. (in Ukrainian).
8. Pan 'kiv VI. Hypothyroidism syndrome. Mezhdunarodnyi Endokrinologicheskii Zhurnal. 2012;5(45):136-148. (in Ukrainian).
504
Mi>KHapOAHHI/l eHAOKpMHOAOrÍMHMM XypHaA, p-ISSN 2224-0721, e-ISSN 2307-1427
TOM 13, № 7, 2017
iEI_
9. Podzolkov AV, Fadeyev VV. Hypothyroidism, subclinical hypothyroidism, high-normal TSH level. Klinicheskaia i eksperi-mentalnaia tiroidologia. 2009;5(2):4-17. (in Russian).
10. Prystupjuk OM. Hypothyroidism: failure of organs and systems. Mezhdunarodnyi Endokrinologicheskii Zhurnal. 2011;4(36):104-109. (in Ukrainian).
11. Chaker L, Baumgartner C, den Elzen WP, et al. Sub-clunical hypothyroidism and the risk. Thyroid J. 2014;3(1):96. J Clin Endocrinol Metab. 2015 Jun;100(6):2181-91. doi: 10.1210/ jc.2015-1438.
12. Fernandez-Real JM, Lopez-Bermejo A, Castro A, Casa-mitjana R, Ricart W. Thyroid function is intrinsically linked to insulin sensitivity and endothelium-dependent vasodilation in healthy euthyroid subjects. J Clin Endocrinol Metab. 2006 Sep;91(9):3337-43. doi: 10.1210/jc.2006-0841.
13. Gullo AC, Latina A, Frasca F, Le Moli R, Pelegriti G, Vigneri R. Levothyroxine monotherapy cannot guarantee euthy-roidizm in all athyreotic patients. PLoS One. 2011;6(8):e22552. doi: 10.1371/journal.pone.0022552.
14. Malyszko J, Malyszko JS, Pawlak K, Mysliwiec M. Thyroid function, endothelium, and inflammation in hemodialyzed patients: possible relations? J Ren Nutr. 2007Jan;17(1):30-7. doi: 10.1053/j.jrn.2006.07.003.
Огляд лператури /Literature Review/
15. Rizos CV, Elisaf MS, Liberopoulos EN. Effects of Thyroid Dysfunction on Lipid Profile. Open Cardiovasc Med J. 2011;5:76-84. doi: 10.2174/1874192401105010076.
16. Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010 Sep 22;304(12):1365-74. doi: 10.1001/ jama.2010.1361.
17. Rush J, Danzi SM, Klein I. Role of thyroid disease in the development of statin-induced myopathy. Endocrinologist. 2006;16:279-285. doi: 10.1097/01.ten.0000240960.40281.2b.
18. Shrestha N. Thyroid dysfunction and its effect in serum lipids. J Nepal Health Res Counc. 2011 Apr;9(1):33-7. PMID: 22929710.
19. Sunanda V, Sangeeta S, Prabhakar B. Study of lipid profile in hypothyroidism. Int J Biol Med Res. 2012;3(1):1373-1376.
20. Volkova A, Dora S, Berkovich O, Grineva E, Dygun O. Predictive risk model of severe coronary atherosclerosis in heart ischemic disease patients with subclinical hypothyroidism. In: 38th Annual Meeting of the European Thyroid Association. 2014 September 6-10; Santiago de Compostela, Spain. Eur Thyroid J. 2014 Aug;3(Suppl 1):152. P148. doi: 10.1159/000365244.
Recerved 02.10.2017 ■
Городинська О.Ю.
Вищий державний навчальний заклад Украни «Укранська медична стоматолопчна академiя», м. Полтава, Украна
Синдром ппотиреозу як фактор розвитку патологи серцево-судинноТ системи
(огляд л^ератури)
Резюме. У статп наведеш даш про патогенетичш аспекта розвитку патологи серцево-судинно! системи при зни-женш функци щитоподiбноi залози. Ппотиреоз асоцш-еться з пщвищенням ризику розвитку iшемiчноi хвороби серця, шфаркгу мюкарда, хрошчно! серцево! недостат-носп й смертност вщ серцево-судинних захворювань не-
залежно вщ стат1, в1ку и попереднгх серцево-судинних захворювань. Це спонукае до пошуку додаткового впливу на патогенетичш мехашзми ппотиреозу з метою ефективно! терапи вказаних загрозливих прояв1в та наслщшв хвороби. Krn40Bi слова: ппотиреоз; шем1чна хвороба серця; огляд
Городинская Е.Ю.
Высшее государственное учебное заведение Украины «Украинская медицинская стоматологическая академия», г. Полтава, Украина
Синдром гипотиреоза как фактор развития патологии сердечно-сосудистой системы
(обзор литературы)
Резюме. В статье приведены данные о патогенетических аспектах развития патологии сердечно-сосудистой системы при снижении функции щитовидной железы. Гипотиреоз ассоциируется с повышением риска развития ишемической болезни сердца, инфаркта миокарда, хронической сердечной недостаточности и смертности от сердечно-сосудистых заболеваний независимо от пола,
возраста и предыдущих сердечно-сосудистых заболеваний. Это побуждает к поиску дополнительного воздействия на патогенетические механизмы гипотиреоза с целью эффективной терапии указанных угрожающих проявлений и последствий болезни.
Ключевые слова: гипотиреоз; ишемическая болезнь сердца; обзор
