Thyroid hormones have a direct effect on the heart
Patients with hypothyroidism or hyperthyroidism have increased risk of cardiovascular disease
Treatment with thyroid hormones in patients with hypothyroidism improves cardiovascular risk factors, but the effect on cardiovascular events has not been assessed in randomized, controlled trials
In experimental settings, thyroid hormones influence myocardial remodelling and function after myocardial infarction, but the utility of thyroid hormone replacement therapy in patients with acute cardiac events is yet to be elucidated
Intracellular and circulating thyroid hormone concentrations (mainly T3) decrease after acute myocardial infarction and in chronic heart failure, and this reduction is associated with poor outcomes
Small studies showed that treatment with thyroid hormones is safe and beneficial in patients with chronic heart failure; however, larger, adequately powered trials are required to confirm safety and assess efficacy
Myocardial and vascular endothelial tissues have receptors for thyroid hormones and are sensitive to changes in the concentrations of circulating thyroid hormones. The importance of thyroid hormones in maintaining cardiovascular homeostasis can be deduced from clinical and experimental data showing that even subtle changes in thyroid hormone concentrations — such as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome — adversely influence the cardiovascular system. Some potential mechanisms linking the two conditions are dyslipidaemia, endothelial dysfunction, blood pressure changes, and direct effects of thyroid hormones on the myocardium. Several interventional trials showed that treatment of subclinical thyroid diseases improves cardiovascular risk factors, which implies potential benefits for reducing cardiovascular events. Over the past 2 decades, accumulating evidence supports the association between abnormal thyroid function at the time of an acute myocardial infarction (MI) and subsequent adverse cardiovascular outcomes. Furthermore, experimental studies showed that thyroid hormones can have an important therapeutic role in reducing infarct size and improving myocardial function after acute MI. In this Review, we summarize the literature on thyroid function in cardiovascular diseases, both as a risk factor as well as in the setting of cardiovascular diseases such as heart failure or acute MI, and outline the effect of thyroid hormone replacement therapy for reducing the risk of cardiovascular disease.
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Mozaffarian, D. et al. Heart disease and stroke statistics — 2015 update: a report from the American Heart Association. Circulation 131, e29–e322 (2015).
World Health Organization. Global status report on noncommunicable diseases. WHO http://www.who.int/nmh/publications/ncd_report_full_en.pdf (2010).
Townsend, N., Nichols, M., Scarborough, P. & Rayner, M. Cardiovascular disease in Europe 2015: epidemiological update. Eur. Heart J. 36, 2673–2674 (2015).
Klein, I. & Ojamaa, K. Thyroid hormone and the cardiovascular system. N. Engl. J. Med. 344, 501–509 (2001).
Allahabadia, A., Razvi, S., Abraham, P. & Franklyn, J. Diagnosis and treatment of primary hypothyroidism. BMJ 338, b725 (2009).
Hak, A. E. et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann. Intern. Med. 132, 270–278 (2000).
Walsh, J. P. et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch. Intern. Med. 165, 2467–2472 (2005).
Razvi, S., Weaver, J. U., Vanderpump, M. P. & Pearce, S. H. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham Survey cohort. J. Clin. Endocrinol. Metab. 95, 1734–1740 (2010).
Parle, J. V., Maisonneuve, P., Sheppard, M. C., Boyle, P. & Franklyn, J. A. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 358, 861–865 (2001).
Cappola, A. R. et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 295, 1033–1041 (2006).
Canaris, G. J., Manowitz, N. R., Mayor, G. & Ridgway, E. C. The Colorado thyroid disease prevalence study. Arch. Intern. Med. 160, 526–534 (2000).
Laurberg, P. et al. Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark. J. Clin. Endocrinol. Metab. 83, 765–769 (1998).
Vadiveloo, T., Donnan, P. T., Cochrane, L. & Leese, G. P. The Thyroid Epidemiology, Audit, and Research Study (TEARS): the natural history of endogenous subclinical hyperthyroidism. J. Clin. Endocrinol. Metab. 96, E1–E8 (2011).
Ord, W. M. On myxoedema, a term proposed to be applied to an essential condition in the “cretinoid” affection occasionally observed in middle-aged women. Med. Chir. Trans. 61, 57–78.5 (1878).
Kocher, T. Ueber Kropfexstirpation und ihre Folgen. Arch. Klin. Chir. 29, 254–337 (in German) (1883).
Hun, H. & Prudden, T. M. Myxoedema. Four cases, with two autopsies. With a report of the microscopical examination. Am. J. Med. Sci. 96, 1–24 (1888).
Murray, G. R. Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. Br. Med. J. 2, 796–797 (1891).
Slater, S. The discovery of thyroid replacement therapy. Part 3: a complete transformation. J. R. Soc. Med. 104, 100–106 (2011).
Barnes, B. O. Prophylaxis of ischaemic heart-disease by thyroid therapy. Lancet 2, 149–152 (1959).
Barnes, B. O. On the genesis of atherosclerosis. J. Am. Geriatr. Soc. 21, 350–354 (1973).
Kountz, W. B. Vascular degeneration in hypothyroidism. AMA Arch. Pathol. 50, 765–777 (1950).
Utiger, R. D. Radioimmunoassay of human plasma thyrotropin. J. Clin. Invest. 44, 1277–1286 (1965).
Vanhaelst, L., Neve, P. & Bastenie, P. A. Coronary-artery disease in myxoedema. Lancet 2, 1257–1258 (1967).
Vanhaelst, L., Neve, P., Chailly, P. & Bastenie, P. A. Coronary-artery disease in hypothyroidism. Observations in clinical myxoedema. Lancet 2, 800–802 (1967).
Tunbridge, W. M. et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin. Endocrinol. (Oxf.) 7, 481–493 (1977).
The Coronary Drug Project Research Group. The coronary drug project. Findings leading to further modifications of its protocol with respect to dextrothyroxine. JAMA 220, 996–1008 (1972).
Brenta, G., Danzi, S. & Klein, I. Potential therapeutic applications of thyroid hormone analogs. Nat. Clin. Pract. Endocrinol. Metab. 3, 632–640 (2007).
Stamler, J. The coronary drug project — findings with regard to estrogen, dextrothyroxine, clofibrate and niacin. Adv. Exp. Med. Biol. 82, 52–75 (1977).
Pingitore, A., Chen, Y., Gerdes, A. M. & Iervasi, G. Acute myocardial infarction and thyroid function: new pathophysiological and therapeutic perspectives. Ann. Med. 44, 745–757 (2012).
Goldman, S. et al. DITPA (3,5-diiodothyropropionic acid), a thyroid hormone analog to treat heart failure: phase II trial veterans affairs cooperative study. Circulation 119, 3093–3100 (2009).
Ladenson, P. W. et al. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N. Engl. J. Med. 362, 906–916 (2010).
Sjouke, B. et al. Eprotirome in patients with familial hypercholesterolaemia (the AKKA trial): a randomised, double-blind, placebo-controlled phase 3 study. Lancet Diabetes Endocrinol. 2, 455–463 (2014).
Samuels, H. H., Tsai, J. S., Casanova, J. & Stanley, F. Thyroid hormone action: in vitro characterization of solubilized nuclear receptors from rat liver and cultured GH1 cells. J. Clin. Invest. 54, 853–865 (1974).
Davis, P. J., Davis, F. B., Mousa, S. A., Luidens, M. K. & Lin, H. Y. Membrane receptor for thyroid hormone: physiologic and pharmacologic implications. Annu. Rev. Pharmacol. Toxicol. 51, 99–115 (2011).
Gereben, B. et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr. Rev. 29, 898–938 (2008).
Croteau, W., Davey, J. C., Galton, V. A. & St Germain, D. L. Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. J. Clin. Invest. 98, 405–417 (1996).
Salvatore, D., Bartha, T., Harney, J. W. & Larsen, P. R. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology 137, 3308–3315 (1996).
Pol, C. J. et al. Left-ventricular remodeling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology 152, 669–679 (2011).
Cooper, D. S. & Biondi, B. Subclinical thyroid disease. Lancet 379, 1142–1154 (2012).
Brent, G. A. Mechanisms of thyroid hormone action. J. Clin. Invest. 122, 3035–3043 (2012).
Cheng, S. Y., Leonard, J. L. & Davis, P. J. Molecular aspects of thyroid hormone actions. Endocr. Rev. 31, 139–170 (2010).
Brent, G. A. The molecular basis of thyroid hormone action. N. Engl. J. Med. 331, 847–853 (1994).
He, H. et al. Overexpression of the rat sarcoplasmic reticulum Ca2+ ATPase gene in the heart of transgenic mice accelerates calcium transients and cardiac relaxation. J. Clin. Invest. 100, 380–389 (1997).
Holt, E., Sjaastad, I., Lunde, P. K., Christensen, G. & Sejersted, O. M. Thyroid hormone control of contraction and the Ca2+-ATPase/phospholamban complex in adult rat ventricular myocytes. J. Mol. Cell. Cardiol. 31, 645–656 (1999).
Kaasik, A., Paju, K., Vetter, R. & Seppet, E. K. Thyroid hormones increase the contractility but suppress the effects of β-adrenergic agonist by decreasing phospholamban expression in rat atria. Cardiovasc. Res. 35, 106–112 (1997).
Nadal-Ginard, B. & Mahdavi, V. Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches. J. Clin. Invest. 84, 1693–1700 (1989).
Fazio, S., Palmieri, E. A., Lombardi, G. & Biondi, B. Effects of thyroid hormone on the cardiovascular system. Recent Prog. Horm. Res. 59, 31–50 (2004).
Ojamaa, K., Klemperer, J. D. & Klein, I. Acute effects of thyroid hormone on vascular smooth muscle. Thyroid 6, 505–512 (1996).
Kranias, E. G. & Hajjar, R. J. Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome. Circ. Res. 110, 1646–1660 (2012).
Kiss, E., Jakab, G., Kranias, E. G. & Edes, I. Thyroid hormone-induced alterations in phospholamban protein expression. Regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation. Circ. Res. 75, 245–251 (1994).
Hoit, B. D. et al. Effects of thyroid hormone on cardiac beta-adrenergic responsiveness in conscious baboons. Circulation 96, 592–598 (1997).
Kuzman, J. A., Gerdes, A. M., Kobayashi, S. & Liang, Q. Thyroid hormone activates Akt and prevents serum starvation-induced cell death in neonatal rat cardiomyocytes. J. Mol. Cell. Cardiol. 39, 841–844 (2005).
Marin-Garcia, J. Thyroid hormone and myocardial mitochondrial biogenesis. Vascul. Pharmacol. 52, 120–130 (2010).
Madathil, A. et al. Levothyroxine improves abnormal cardiac bioenergetics in subclinical hypothyroidism: a cardiac magnetic resonance spectroscopic study. J. Clin. Endocrinol. Metab. 100, E607–E610 (2015).
Park, K. W. et al. The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries. Anesth. Analg. 85, 734–738 (1997).
Silva, J. E. Thyroid hormone control of thermogenesis and energy balance. Thyroid 5, 481–492 (1995).
Feldman, T., Borow, K. M., Sarne, D. H., Neumann, A. & Lang, R. M. Myocardial mechanics in hyperthyroidism: importance of left ventricular loading conditions, heart rate and contractile state. J. Am. Coll. Cardiol. 7, 967–974 (1986).
Klemperer, J. D. et al. Thyroid hormone treatment after coronary-artery bypass surgery. N. Engl. J. Med. 333, 1522–1527 (1995).
Resnick, L. M. & Laragh, J. H. Plasma renin activity in syndromes of thyroid hormone excess and deficiency. Life Sci. 30, 585–586 (1982).
Nakazawa, H. K., Sakurai, K., Hamada, N., Momotani, N. & Ito, K. Management of atrial fibrillation in the post-thyrotoxic state. Am. J. Med. 72, 903–906 (1982).
Biondi, B. Mechanisms in endocrinology: heart failure and thyroid dysfunction. Eur. J. Endocrinol. 167, 609–618 (2012).
Franklyn, J. A., Sheppard, M. C. & Maisonneuve, P. Thyroid function and mortality in patients treated for hyperthyroidism. JAMA 294, 71–80 (2005).
Marvisi, M. et al. Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. Eur. J. Intern. Med. 17, 267–271 (2006).
Suk, J. H. et al. Prevalence of echocardiographic criteria for the diagnosis of pulmonary hypertension in patients with Graves' disease: before and after antithyroid treatment. J. Endocrinol. Invest. 34, e229–e234 (2011).
Al Husseini, A. et al. Thyroid hormone is highly permissive in angioproliferative pulmonary hypertension in rats. Eur. Respir. J. 41, 104–114 (2013).
Davis, F. B. et al. Proangiogenic action of thyroid hormone is fibroblast growth factor-dependent and is initiated at the cell surface. Circ. Res. 94, 1500–1506 (2004).
Surks, M. I. et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 291, 228–238 (2004).
Gharib, H. et al. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J. Clin. Endocrinol. Metab. 90, 581–585 (2005).
Biondi, B. & Cooper, D. S. The clinical significance of subclinical thyroid dysfunction. Endocr. Rev. 29, 76–131 (2008).
Bahn, R. S. et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr. Pract. 17, 456–520 (2011).
Parle, J. V., Franklyn, J. A., Cross, K. W., Jones, S. R. & Sheppard, M. C. Thyroxine prescription in the community: serum thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment. Br. J. Gen. Pract. 43, 107–109 (1993).
Okosieme, O. E., Belludi, G., Spittle, K., Kadiyala, R. & Richards, J. Adequacy of thyroid hormone replacement in a general population. QJM 104, 395–401 (2011).
Taylor, P. N. et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern. Med. 174, 32–39 (2014).
Vadiveloo, T., Donnan, P. T., Cochrane, L. & Leese, G. P. The Thyroid Epidemiology, Audit, and Research Study (TEARS): morbidity in patients with endogenous subclinical hyperthyroidism. J. Clin. Endocrinol. Metab. 96, 1344–1351 (2011).
Biondi, B. et al. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients. J. Clin. Endocrinol. Metab. 85, 4701–4705 (2000).
Sgarbi, J. A., Villaca, F. G., Garbeline, B., Villar, H. E. & Romaldini, J. H. The effects of early antithyroid therapy for endogenous subclinical hyperthyroidism in clinical and heart abnormalities. J. Clin. Endocrinol. Metab. 88, 1672–1677 (2003).
Pearce, E. N., Yang, Q., Benjamin, E. J., Aragam, J. & Vasan, R. S. Thyroid function and left ventricular structure and function in the Framingham Heart Study. Thyroid 20, 369–373 (2010).
Dorr, M. et al. Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up. Clin. Endocrinol. (Oxf.) 73, 821–826 (2010).
Volzke, H. et al. Thyroid function and carotid wall thickness. J. Clin. Endocrinol. Metab. 89, 2145–2149 (2004).
Dorr, M. et al. Low serum thyrotropin is associated with high plasma fibrinogen. J. Clin. Endocrinol. Metab. 91, 530–534 (2006).
Iervasi, G. et al. Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch. Intern. Med. 167, 1526–1532 (2007).
Sawin, C. T. Subclinical hyperthyroidism and atrial fibrillation. Thyroid 12, 501–503 (2002).
Auer, J. & Eber, B. Subclinical hyperthyroidism and atrial fibrillation. Acta Med. Austriaca 30, 98–99 (in German) (2003).
Gammage, M. D. et al. Association between serum free thyroxine concentration and atrial fibrillation. Arch. Intern. Med. 167, 928–934 (2007).
Collet, T. H. et al. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch. Intern. Med. 172, 799–809 (2012).
Rodondi, N. et al. Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure: the Cardiovascular Health Study. J. Am. Coll. Cardiol. 52, 1152–1159 (2008).
Chaker, L. et al. Normal thyroid function and the risk of atrial fibrillation: the Rotterdam Study. J. Clin. Endocrinol. Metab. 100, 3718–3724 (2015).
Cappola, A. R. et al. Thyroid function in the euthyroid range and adverse outcomes in older adults. J. Clin. Endocrinol. Metab. 100, 1088–1096 (2015).
Heeringa, J. et al. High-normal thyroid function and risk of atrial fibrillation: the Rotterdam Study. Arch. Intern. Med. 168, 2219–2224 (2008).
Flynn, R. W. et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J. Clin. Endocrinol. Metab. 95, 186–193 (2010).
van den Beld, A. W., Visser, T. J., Feelders, R. A., Grobbee, D. E. & Lamberts, S. W. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J. Clin. Endocrinol. Metab. 90, 6403–6409 (2005).
Biondi, B. et al. The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. Eur. Thyroid J. 4, 149–163 (2015).
Tunbridge, W. M. et al. Lipid profiles and cardiovascular disease in the Whickham area with particular reference to thyroid failure. Clin. Endocrinol. (Oxf.) 7, 495–508 (1977).
Klein, I. & Danzi, S. Thyroid disease and the heart. Circulation 116, 1725–1735 (2007).
Cappola, A. R. & Ladenson, P. W. Hypothyroidism and atherosclerosis. J. Clin. Endocrinol. Metab. 88, 2438–2444 (2003).
Hamilton, T. E., Davis, S., Onstad, L. & Kopecky, K. J. Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 93, 1224–1230 (2008).
Hollowell, J. G. et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489–499 (2002).
Parle, J. V., Franklyn, J. A., Cross, K. W., Jones, S. C. & Sheppard, M. C. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin. Endocrinol. (Oxf.) 34, 77–83 (1991).
Monzani, F. et al. Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study. J. Clin. Endocrinol. Metab. 86, 1110–1115 (2001).
Biondi, B. et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 84, 2064–2067 (1999).
Ripoli, A. et al. Does subclinical hypothyroidism affect cardiac pump performance? Evidence from a magnetic resonance imaging study. J. Am. Coll. Cardiol. 45, 439–445 (2005).
Brenta, G. et al. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to l-thyroxine therapy. Am. J. Cardiol. 91, 1327–1330 (2003).
Kahaly, G. J. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 10, 665–679 (2000).
Owen, P. J., Sabit, R. & Lazarus, J. H. Thyroid disease and vascular function. Thyroid 17, 519–524 (2007).
Boekholdt, S. M. et al. Initial thyroid status and cardiovascular risk factors: the EPIC-Norfolk prospective population study. Clin. Endocrinol. (Oxf.) 72, 404–410 (2010).
McQuade, C. et al. 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, 837–843 (2011).
Rodondi, N. et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch. Intern. Med. 165, 2460–2466 (2005).
Rodondi, N. et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304, 1365–1374 (2010).
Jabbar, A. & Razvi, S. Thyroid disease and vascular risk. Clin. Med. (Lond.) 14, s29–s32 (2014).
Razvi, S., Shakoor, A., Vanderpump, M., Weaver, J. U. & Pearce, S. H. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J. Clin. Endocrinol. Metab. 93, 2998–3007 (2008).
Razvi, S., Weaver, J. U., Butler, T. J. & Pearce, S. H. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch. Intern. Med. 172, 811–817 (2012).
Pearce, S. H. et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur. Thyroid J. 2, 215–228 (2013).
Parle, J. V., Franklyn, J. A., Cross, K. W., Jones, S. R. & Sheppard, M. C. Circulating lipids and minor abnormalities of thyroid function. Clin. Endocrinol. (Oxf.) 37, 411–414 (1992).
Duntas, L. H. Thyroid disease and lipids. Thyroid 12, 287–293 (2002).
Ineck, B. A. & Ng, T. M. Effects of subclinical hypothyroidism and its treatment on serum lipids. Ann. Pharmacother. 37, 725–730 (2003).
Hueston, W. J. & Pearson, W. S. Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann. Fam. Med. 2, 351–355 (2004).
Asvold, B. O., Vatten, L. J., Nilsen, T. I. & Bjoro, T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Eur. J. Endocrinol. 156, 181–186 (2007).
Pandak, W. M. et al. Hormonal regulation of cholesterol 7α-hydroxylase specific activity, mRNA levels, and transcriptional activity in vivo in the rat. J. Lipid Res. 38, 2483–2491 (1997).
Razvi, S. et al. 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. 92, 1715–1723 (2007).
Caraccio, N., Ferrannini, E. & Monzani, F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J. Clin. Endocrinol. Metab. 87, 1533–1538 (2002).
Monzani, F. et al. Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. J. Clin. Endocrinol. Metab. 89, 2099–2106 (2004).
Jaeschke, R. et al. Does treatment with l-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? J. Gen. Intern. Med. 11, 744–749 (1996).
Kong, W. M. et al. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am. J. Med. 112, 348–354 (2002).
Danese, M. D., Ladenson, P. W., Meinert, C. L. & Powe, N. R. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J. Clin. Endocrinol. Metab. 85, 2993–3001 (2000).
Villar, H. C., Saconato, H., Valente, O. & Atallah, A. N. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database Syst. Rev. 3, CD003419 (2007).
Iqbal, A., Jorde, R. & Figenschau, Y. Serum lipid levels in relation to serum thyroid-stimulating hormone and the effect of thyroxine treatment on serum lipid levels in subjects with subclinical hypothyroidism: the Tromsø study. J. Intern. Med. 260, 53–61 (2006).
Danzi, S. & Klein, I. Thyroid hormone and blood pressure regulation. Curr. Hypertens. Rep. 5, 513–520 (2003).
Ching, G. W. et al. Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis. Heart 75, 363–368 (1996).
Volzke, H. et al. Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study. Eur. J. Endocrinol. 161, 615–621 (2009).
Cai, Y., Ren, Y. & Shi, J. Blood pressure levels in patients with subclinical thyroid dysfunction: a meta-analysis of cross-sectional data. Hypertens. Res. 34, 1098–1105 (2011).
Volzke, H. et al. The association between subclinical hyperthyroidism and blood pressure in a population-based study. J. Hypertens. 24, 1947–1953 (2006).
Walsh, J. P. et al. Subclinical thyroid dysfunction and blood pressure: a community-based study. Clin. Endocrinol. (Oxf.) 65, 486–491 (2006).
Osman, F., Franklyn, J. A., Holder, R. L., Sheppard, M. C. & Gammage, M. D. Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study. J. Am. Coll. Cardiol. 49, 71–81 (2007).
Saito, I., Ito, K. & Saruta, T. Hypothyroidism as a cause of hypertension. Hypertension 5, 112–115 (1983).
Fommei, E. & Iervasi, G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J. Clin. Endocrinol. Metab. 87, 1996–2000 (2002).
Iqbal, A., Figenschau, Y. & Jorde, R. Blood pressure in relation to serum thyrotropin: the Tromsø study. J. Hum. Hypertens. 20, 932–936 (2006).
Dart, A. M. et al. Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant. Lancet 338, 270–273 (1991).
Laurent, S. et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 37, 1236–1241 (2001).
Dernellis, J. & Panaretou, M. Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism. Am. Heart J. 143, 718–724 (2002).
Obuobie, K. et al. Increased central arterial stiffness in hypothyroidism. J. Clin. Endocrinol. Metab. 87, 4662–4666 (2002).
Nagasaki, T. et al. Increased pulse wave velocity in subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 91, 154–158 (2006).
Nagasaki, T. et al. Changes in brachial-ankle pulse wave velocity in subclinical hypothyroidism during normalization of thyroid function. Biomed. Pharmacother. 61, 482–487 (2007).
Nagasaki, T. et al. Decrease of brachial-ankle pulse wave velocity in female subclinical hypothyroid patients during normalization of thyroid function: a double-blind, placebo-controlled study. Eur. J. Endocrinol. 160, 409–415 (2009).
Lerman, A. & Zeiher, A. M. Endothelial function: cardiac events. Circulation 111, 363–368 (2005).
Lekakis, J. et al. Flow-mediated, endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values. Thyroid 7, 411–414 (1997).
Taddei, S. et al. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J. Clin. Endocrinol. Metab. 88, 3731–3737 (2003).
Taddei, S. et al. Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis. J. Clin. Endocrinol. Metab. 91, 5076–5082 (2006).
Kvetny, J., Heldgaard, P. E., Bladbjerg, E. M. & Gram, J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin. Endocrinol. (Oxf.) 61, 232–238 (2004).
Turemen, E. E., Cetinarslan, B., Sahin, T., Canturk, Z. & Tarkun, I. Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr. J. 58, 349–354 (2011).
Cikim, A. S. et al. Evaluation of endothelial function in subclinical hypothyroidism and subclinical hyperthyroidism. Thyroid 14, 605–609 (2004).
Marazuela, M., Sanchez-Madrid, F., Acevedo, A., Larranaga, E. & de Landazuri, M. O. Expression of vascular adhesion molecules on human endothelia in autoimmune thyroid disorders. Clin. Exp. Immunol. 102, 328–334 (1995).
Suarez, J. et al. In vivo selective expression of thyroid hormone receptor α1 in endothelial cells attenuates myocardial injury in experimental myocardial infarction in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307, R340–R346 (2014).
Carrillo-Sepulveda, M. A. et al. Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. Cardiovasc. Res. 85, 560–570 (2010).
Wang, X., Zheng, W., Christensen, L. P. & Tomanek, R. J. DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth. Am. J. Physiol. Heart Circ. Physiol. 284, H613—H618 (2003).
Tomanek, R. J., Doty, M. K. & Sandra, A. Early coronary angiogenesis in response to thyroxine: growth characteristics and upregulation of basic fibroblast growth factor. Circ. Res. 82, 587–593 (1998).
Erem, C. Blood coagulation, fibrinolytic activity and lipid profile in subclinical thyroid disease: subclinical hyperthyroidism increases plasma factor X activity. Clin. Endocrinol. (Oxf.) 64, 323–329 (2006).
Franchini, M., Lippi, G. & Targher, G. Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review. Clin. Appl. Thromb. Hemostasis 17, 387–392 (2011).
Dorr, M. et al. The association of thyroid function with carotid artery plaque burden and strokes in a population-based sample from a previously iodine-deficient area. Eur. J. Endocrinol. 159, 145–152 (2008).
Muller, B. et al. Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. Eur. J. Clin. Invest. 31, 131–137 (2001).
Canturk, Z. et al. Hemostatic system as a risk factor for cardiovascular disease in women with subclinical hypothyroidism. Thyroid 13, 971–977 (2003).
Viswanathan, G. et al. Blood thrombogenicity is independently associated with serum TSH levels in post-non-ST elevation acute coronary syndrome. J. Clin. Endocrinol. Metab. 99, E1050–E1054 (2014).
Squizzato, A., Gerdes, V. E., Brandjes, D. P., Buller, H. R. & Stam, J. Thyroid diseases and cerebrovascular disease. Stroke 36, 2302–2310 (2005).
Erem, C. et al. Blood coagulation and fibrinolytic activity in hypothyroidism. Int. J. Clin. Pract. 57, 78–81 (2003).
Nitu-Whalley, I. C. & Lee, C. A. Acquired von Willebrand syndrome — report of 10 cases and review of the literature. Haemophilia 5, 318–326 (1999).
Michiels, J. J., Schroyens, W., Berneman, Z. & van der Planken, M. Acquired von Willebrand syndrome type 1 in hypothyroidism: reversal after treatment with thyroxine. Clin. Appl. Thromb. Hemostasis 7, 113–115 (2001).
Gullu, S., Sav, H. & Kamel, N. Effects of levothyroxine treatment on biochemical and hemostasis parameters in patients with hypothyroidism. Eur. J. Endocrinol. 152, 355–361 (2005).
Chadarevian, R. et al. Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism. J. Clin. Endocrinol. Metab. 86, 732–737 (2001).
Virtanen, V. K., Saha, H. H., Groundstroem, K. W., Salmi, J. & Pasternack, A. I. Thyroid hormone substitution therapy rapidly enhances left-ventricular diastolic function in hypothyroid patients. Cardiology 96, 59–64 (2001).
Tielens, E. T., Pillay, M., Storm, C. & Berghout, A. Changes in cardiac function at rest before and after treatment in primary hypothyroidism. Am. J. Cardiol. 85, 376–380 (2000).
Aghini-Lombardi, F. et al. Early textural and functional alterations of left ventricular myocardium in mild hypothyroidism. Eur. J. Endocrinol. 155, 3–9 (2006).
Yazici, M. et al. Effects of thyroxin therapy on cardiac function in patients with subclinical hypothyroidism: index of myocardial performance in the evaluation of left ventricular function. Int. J. Cardiol. 95, 135–143 (2004).
Simonides, W. S. et al. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. J. Clin. Invest. 118, 975–983 (2008).
Diano, S. & Horvath, T. L. Type 3 deiodinase in hypoxia: to cool or to kill? Cell Metab. 7, 363–364 (2008).
Silva-Tinoco, R. et al. Developing thyroid disorders is associated with poor prognosis factors in patient with stable chronic heart failure. Int. J. Cardiol. 147, e24–e25 (2011).
Passino, C. et al. Prognostic value of combined measurement of brain natriuretic peptide and triiodothyronine in heart failure. J. Card. Fail. 15, 35–40 (2009).
Iacoviello, M. et al. Prognostic role of sub-clinical hypothyroidism in chronic heart failure outpatients. Curr. Pharm. Design 14, 2686–2692 (2008).
Iervasi, G. et al. Low-T3 syndrome: a strong prognostic predictor of death in patients with heart disease. Circulation 107, 708–713 (2003).
Pingitore, A. et al. Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am. J. Med. 118, 132–136 (2005).
Chuang, C. P., Jong, Y. S., Wu, C. Y. & Lo, H. M. Impact of triiodothyronine and N-terminal pro-B-type natriuretic peptide on the long-term survival of critically ill patients with acute heart failure. Am. J. Cardiol. 113, 845–850 (2014).
Hamilton, M. A. et al. Safety and hemodynamic effects of intravenous triiodothyronine in advanced congestive heart failure. Am. J. Cardiol. 81, 443–447 (1998).
Pingitore, A. et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J. Clin. Endocrinol. Metab. 93, 1351–1358 (2008).
James, S. R. et al. The effects of acute triiodothyronine therapy on myocardial gene expression in brain stem dead cardiac donors. J. Clin. Endocrinol. Metab. 95, 1338–1343 (2010).
Holmager, P. et al. Long-term L-triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study. Clin. Endocrinol. (Oxf.) 83, 931–937 (2015).
Moruzzi, P., Doria, E., Agostoni, P. G., Capacchione, V. & Sganzerla, P. Usefulness of l-thyroxine to improve cardiac and exercise performance in idiopathic dilated cardiomyopathy. Am. J. Cardiol. 73, 374–378 (1994).
Moruzzi, P., Doria, E. & Agostoni, P. G. Medium-term effectiveness of l-thyroxine treatment in idiopathic dilated cardiomyopathy. Am. J. Med. 101, 461–467 (1996).
Yu, J. & Koenig, R. J. Regulation of hepatocyte thyroxine 5′-deiodinase by T3 and nuclear receptor coactivators as a model of the sick euthyroid syndrome. J. Biol. Chem. 275, 38296–38301 (2000).
Lim, A. S., Paz-Pacheco, E., Reyes, M. & Punzalan, F. Pericardial decompression syndrome in a patient with hypothyroidism presenting as massive pericardial effusion: a case report and review of related literature. BMJ Case Rep. http://dx.doi.org/10.1136/bcr.04.2011.4117 (2011).
Kabadi, U. M. & Kumar, S. P. Pericardial effusion in primary hypothyroidism. Am. Heart J. 120, 1393–1395 (1990).
Sachdev, Y. & Hall, R. Effusions into body cavities in hypothyroidism. Lancet 1, 564–566 (1975).
Iacobellis, G. & Sharma, A. M. Epicardial adipose tissue as new cardio-metabolic risk marker and potential therapeutic target in the metabolic syndrome. Curr. Pharm. Design 13, 2180–2184 (2007).
Jeong, J. W. et al. Echocardiographic epicardial fat thickness and coronary artery disease. Circ. J. 71, 536–539 (2007).
Baker, A. R. et al. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc. Diabetol. 5, 1 (2006).
Yazici, D. et al. Effects of restoration of the euthyroid state on epicardial adipose tissue and carotid intima media thickness in subclinical hypothyroid patients. Endocrine 48, 909–915 (2015).
Asik, M. et al. Evaluation of epicardial fat tissue thickness in patients with Hashimoto thyroiditis. Clin. Endocrinol. (Oxf.) 79, 571–576 (2013).
Robuschi, G. et al. Cardiopulmonary bypass: a low T4 and T3 syndrome with blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH). Horm. Res. 23, 151–158 (1986).
Holland, F. W., 2nd, Brown, P. S. Jr, Weintraub, B. D. & Clark, R. E. Cardiopulmonary bypass and thyroid function: a “euthyroid sick syndrome”. Ann. Thorac. Surg. 52, 46–50 (1991).
Novitzky, D. et al. Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery. Cardiology 87, 509–515 (1996).
Cerillo, A. G. et al. The low triiodothyronine syndrome: a strong predictor of low cardiac output and death in patients undergoing coronary artery bypass grafting. Ann. Thorac. Surg. 97, 2089–2095 (2014).
Klemperer, J. D. et al. Triiodothyronine therapy lowers the incidence of atrial fibrillation after cardiac operations. Ann. Thorac. Surg. 61, 1323–1327 (1996).
Haas, N. A., Camphausen, C. K. & Kececioglu, D. Clinical review: thyroid hormone replacement in children after cardiac surgery — is it worth a try? Crit. Care 10, 213 (2006).
Portman, M. A. et al. Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis. Circulation 122, S224–S233 (2010).
Chowdhury, D. et al. A prospective randomized clinical study of thyroid hormone treatment after operations for complex congenital heart disease. J. Thorac. Cardiovasc. Surg. 122, 1023–1025 (2001).
Friberg, L., Werner, S., Eggertsen, G. & Ahnve, S. Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina? Arch. Intern. Med. 162, 1388–1394 (2002).
Li, L. et al. Negative association between free triiodothyronine level and international normalized ratio in euthyroid subjects with acute myocardial infarction. Acta Pharmacol. Sin. 32, 1351–1356 (2011).
Ozcan, K. S. et al. Sick euthyroid syndrome is associated with poor prognosis in patients with ST segment elevation myocardial infarction undergoing primary percutaneous intervention. Cardiol. J. 21, 238–244 (2014).
Ertugrul, O. et al. Prevalence of subclinical hypothyroidism among patients with acute myocardial infarction. ISRN Endocrinol. 2011, 810251 (2011).
Olivares, E. L. et al. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology 148, 4786–4792 (2007).
Van den Berghe, G. Non-thyroidal illness in the ICU: a syndrome with different faces. Thyroid 24, 1456–1465 (2014).
De Groot, L. J. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J. Clin. Endocrinol. Metab. 84, 151–164 (1999).
Zhang, B., Peng, W., Wang, C., Li, W. & Xu, Y. A low fT3 level as a prognostic marker in patients with acute myocardial infarctions. Intern. Med. 51, 3009–3015 (2012).
Friberg, L., Drvota, V., Bjelak, A. H., Eggertsen, G. & Ahnve, S. Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am. J. Med. 111, 699–703 (2001).
Kimur, T. et al. Correlation of circulating interleukin-10 with thyroid hormone in acute myocardial infarction. Res. Commun. Mol. Pathol. Pharmacol. 110, 53–58 (2001).
Lymvaios, I. et al. Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association? Eur. J. Endocrinol. 165, 107–114 (2011).
Pingitore, A. et al. Cardioprotection and thyroid hormones. Heart Failure Rev. 21, 391–399 (2016).
Columbano, A. et al. The thyroid hormone receptor-β agonist GC-1 induces cell proliferation in rat liver and pancreas. Endocrinology 147, 3211–3218 (2006).
Naqvi, N. et al. A proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell 157, 795–807 (2014).
Forini, F. et al. Early long-term L-T3 replacement rescues mitochondria and prevents ischemic cardiac remodelling in rats. J. Cell. Mol. Med. 15, 514–524 (2011).
Dixon, J. A. & Spinale, F. G. Pathophysiology of myocardial injury and remodeling: implications for molecular imaging. J. Nucl. Med. 51, 102S–106S (2010).
Gerdes, A. M. et al. Structural remodeling of cardiac myocytes in patients with ischemic cardiomyopathy. Circulation 86, 426–430 (1992).
Pfeffer, M. A. Left ventricular remodeling after acute myocardial infarction. Annu. Rev. Med. 46, 455–466 (1995).
Ojamaa, K., Kenessey, A., Shenoy, R. & Klein, I. Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Am. J. Physiol. Endocrinol. Metab. 279, E1319–E1324 (2000).
Henderson, K. K. et al. Physiological replacement of T3 improves left ventricular function in an animal model of myocardial infarction-induced congestive heart failure. Circ. Heart Fail. 2, 243–252 (2009).
Katzeff, H. L., Powell, S. R. & Ojamaa, K. Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3 . Am. J. Physiol. 273, E951–E956 (1997).
Willis, B. C. et al. Impaired oxidative metabolism and calcium mishandling underlie cardiac dysfunction in a rat model of post-acute isoproterenol-induced cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol. 308, H467–H477 (2015).
Rybin, V. & Steinberg, S. F. Thyroid hormone represses protein kinase C isoform expression and activity in rat cardiac myocytes. Circ. Res. 79, 388–398 (1996).
Pantos, C. et al. Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion? Basic Res. Cardiol. 104, 69–77 (2009).
Pantos, C. et al. Thyroid hormone and cardioprotection: study of p38 MAPK and JNKs during ischaemia and at reperfusion in isolated rat heart. Mol. Cell. Biochem. 242, 173–180 (2003).
Mourouzis, I. et al. Dose-dependent effects of thyroid hormone on post-ischemic cardiac performance: potential involvement of Akt and ERK signalings. Mol. Cell. Biochem. 363, 235–243 (2012).
Forini, F. et al. Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis. Endocrinology 155, 4581–4590 (2014).
de Castro, A. L. et al. Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction. Apoptosis 21, 184–194 (2016).
Matsumoto, S. et al. Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ. Res. 113, 322–326 (2013).
Eckle, T., Kohler, D., Lehmann, R., El Kasmi, K. & Eltzschig, H. K. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation 118, 166–175 (2008).
Moeller, L. C., Dumitrescu, A. M. & Refetoff, S. Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1α and glycolytic genes. Mol. Endocrinol. 19, 2955–2963 (2005).
Chen, Y. F. et al. Improvement of left ventricular remodeling after myocardial infarction with eight weeks l-thyroxine treatment in rats. J. Transl Med. 11, 40 (2013).
Rajagopalan, V. et al. Safe oral triiodo-l-thyronine therapy protects from post-infarct cardiac dysfunction and arrhythmias without cardiovascular adverse effects. PLoS ONE 11, e0151413 (2016).
De Vito, P. et al. Thyroid hormones as modulators of immune activities at the cellular level. Thyroid 21, 879–890 (2011).
Plow, E. F., Haas, T. A., Zhang, L., Loftus, J. & Smith, J. W. Ligand binding to integrins. J. Biol. Chem. 275, 21785–21788 (2000).
Siddiqi, A., Burrin, J. M., Wood, D. F. & Monson, J. P. Tri-iodothyronine regulates the production of interleukin-6 and interleukin-8 in human bone marrow stromal and osteoblast-like cells. J. Endocrinol. 157, 453–461 (1998).
Mascanfroni, I. et al. Control of dendritic cell maturation and function by triiodothyronine. FASEB J. 22, 1032–1042 (2008).
Wong, G. H. & Goeddel, D. V. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science 242, 941–944 (1988).
Nakano, M., Knowlton, A. A., Yokoyama, T., Lesslauer, W. & Mann, D. L. Tumor necrosis factor-alpha-induced expression of heat shock protein 72 in adult feline cardiac myocytes. Am. J. Physiol. 270, H1231–H1239 (1996).
Finkel, M. S. et al. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257, 387–389 (1992).
Lubrano, V., Pingitore, A., Carpi, A. & Iervasi, G. Relationship between triiodothyronine and proinflammatory cytokines in chronic heart failure. Biomed. Pharmacother. 64, 165–169 (2010).
Kimura, T. et al. Involvement of circulating interleukin-6 and its receptor in the development of euthyroid sick syndrome in patients with acute myocardial infarction. Eur. J. Endocrinol. 143, 179–184 (2000).
Chen, Y. F. et al. Short term triiodo-L-thyronine treatment inhibits cardiac myocyte apoptosis in border area after myocardial infarction in rats. J. Mol. Cell. Cardiol. 44, 180–187 (2008).
Gerdes, A. M. & Iervasi, G. Thyroid replacement therapy and heart failure. Circulation 122, 385–393 (2010).
Jabbar, A., Ingoe, L., Pearce, S., Zaman, A. & Razvi, S. Thyroxine in acute myocardial infarction (ThyrAMI) — levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial. Trials 16, 115 (2015).
Mourouzis, I., Forini, F., Pantos, C. & Iervasi, G. Thyroid hormone and cardiac disease: from basic concepts to clinical application. J. Thyroid Res. 2011, 958626 (2011).
S.R. is supported by a National Institute for Health Research (NIHR) Career Development Fellowship. The work of S.H.S.P. on subclinical hyperthyroidism was funded by MRC Grant G0500783. This report is independent research supported by the National Institute for Health Research Career Development Fellowship CDF−2012–05–231. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health.
The authors declare no competing financial interests.
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Jabbar, A., Pingitore, A., Pearce, S. et al. Thyroid hormones and cardiovascular disease. Nat Rev Cardiol 14, 39–55 (2017). https://doi.org/10.1038/nrcardio.2016.174
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