Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Is Low-free Triiodothyronine (fT3) Associated with Increased Morbidity in Patients Admitted to Coronary Care Units?

In Press, (this is not the final "Version of Record"). Available online 23 April, 2024
Author(s): Oguz Akkus, Fatih Sen, Ramazan Yasdıbas, Alper Tunga Otegen, Irem Huzmeli and Gamze Akkus*
Published on: 23 April, 2024

DOI: 10.2174/0118715303287732240201122412

Price: $95

Abstract

Background: The effects of thyroid hormone on patients hospitalized in coronary intensive care units are still controversial.

Objective: We retrospectively examined thyroid hormone levels and their impact on cardiovascular morbidity in patients admitted to coronary intensive care units.

Methods: A total of 208 (Female/Male; 46.6%/53.4%) patients without any history of thyroid disease were enrolled and screened. Patients with specific heart disease and existing thyroid hormone parameters were included in the study. Low triiodothyronine syndrome is characterized by reduced serum total or free T3 (fT3) concentrations in normal free T4 (fT4) and TSH levels.

Results: The common diagnosis of the patients in the coronary care unit is acute coronary syndrome (n=59, 28.2 %) and heart failure (n=46, 23.3%). Patients were divided into two groups according to left ventricular ejection fraction percentages (LVEF ≤39% vs LVEF ≥40%). Plasma fT3 levels were significantly correlated with low LVEF (≤39%) (p =0.002). fT3 (r=-0.183, p =0.013) and hospitalization etiology (r=-0.161, p =0.023) were also the most critical parameters affecting the length of hospitalization.

Conclusion: Low fT3 was associated with reduced ejection fraction and prolonged hospitalization, which may lead to potential morbidities in HF patients and may be useful in risk stratification and treatment strategies.

[1]
Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.; Cushman, M.; Delling, F.N.; Deo, R.; de Ferranti, S.D.; Ferguson, J.F.; Fornage, M.; Gillespie, C.; Isasi, C.R.; Jiménez, M.C.; Jordan, L.C.; Judd, S.E.; Lackland, D.; Lichtman, J.H.; Lisabeth, L.; Liu, S.; Longenecker, C.T.; Lutsey, P.L.; Mackey, J.S.; Matchar, D.B.; Matsushita, K.; Mussolino, M.E.; Nasir, K.; O’Flaherty, M.; Palaniappan, L.P.; Pandey, A.; Pandey, D.K.; Reeves, M.J.; Ritchey, M.D.; Rodriguez, C.J.; Roth, G.A.; Rosamond, W.D.; Sampson, U.K.A.; Satou, G.M.; Shah, S.H.; Spartano, N.L.; Tirschwell, D.L.; Tsao, C.W.; Voeks, J.H.; Willey, J.Z.; Wilkins, J.T.; Wu, J.H.Y.; Alger, H.M.; Wong, S.S.; Muntner, P. Heart disease and stroke statistics-2018 update: A report from the American Heart Association. Circulation, 2018, 137(12), e67-e492.
[http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID: 29386200]
[2]
Xanthakis, V.; Enserro, D.M.; Murabito, J.M.; Polak, J.F.; Wollert, K.C.; Januzzi, J.L.; Wang, T.J.; Tofler, G.; Vasan, R.S. Ideal cardiovascular health: Associations with biomarkers and subclinical disease and impact on incidence of cardiovascular disease in the Framingham Offspring Study. Circulation, 2014, 130(19), 1676-1683.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.009273] [PMID: 25274000]
[3]
Paschou, S.A.; Bletsa, E.; Stampouloglou, P.K.; Tsigkou, V.; Valatsou, A.; Stefanaki, K.; Kazakou, P.; Spartalis, M.; Spartalis, E.; Oikonomou, E.; Siasos, G. Thyroid disorders and cardiovascular manifestations: An update. Endocrine, 2022, 75(3), 672-683.
[http://dx.doi.org/10.1007/s12020-022-02982-4] [PMID: 35032315]
[4]
Chaker, L.; Razvi, S.; Bensenor, I.M.; Azizi, F.; Pearce, E.N.; Peeters, R.P. Hypothyroidism. Nat. Rev. Dis. Primers, 2022, 8(1), 30.
[http://dx.doi.org/10.1038/s41572-022-00357-7] [PMID: 35589725]
[5]
Giontella, A.; Lotta, L.A.; Overton, J.D.; Baras, A.; Sartorio, A.; Minuz, P.; Gill, D.; Melander, O.; Fava, C. Association of thyroid function with blood pressure and cardiovascular disease: A mendelian randomization. J. Pers. Med., 2021, 11(12), 1306.
[http://dx.doi.org/10.3390/jpm11121306] [PMID: 34945778]
[6]
Mantzouratou, P.; Malaxianaki, E.; Cerullo, D.; Lavecchia, A.M.; Pantos, C.; Xinaris, C.; Mourouzis, I. Thyroid hormone and heart failure: Charting known pathways for cardiac repair/regeneration. Biomedicines, 2023, 11(3), 975.
[http://dx.doi.org/10.3390/biomedicines11030975] [PMID: 36979954]
[7]
Rivas, A.M.; Pena, C.; Kopel, J.; Dennis, J.A.; Nugent, K. Hypertension and hyperthyroidism: Association and pathogenesis. Am. J. Med. Sci., 2021, 361(1), 3-7.
[http://dx.doi.org/10.1016/j.amjms.2020.08.012] [PMID: 33012487]
[8]
Vidili, G.; Delitala, A.; Manetti, R. Subclinical hyperthyroidism: The cardiovascular point of view. Eur. Rev. Med. Pharmacol. Sci., 2021, 25(8), 3264-3271.
[http://dx.doi.org/10.26355/eurrev_202104_25735] [PMID: 33928612]
[9]
Liu, G.; Ren, M.; Du, Y.; Zhao, R.; Wu, Y.; Liu, Y.; Qi, L. Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: A meta-analysis. Front. Endocrinol., 2023, 14, 1263861.
[http://dx.doi.org/10.3389/fendo.2023.1263861] [PMID: 37818087]
[10]
Kaushik, A.; Agrawal, M. Relationship between subclinical hypothyroidism and the risk of cardiovascular complications. Cureus, 2023, 15(1), e33708.
[http://dx.doi.org/10.7759/cureus.33708] [PMID: 36788909]
[11]
Feldt-Rasmussen, U.; Effraimidis, G.; Bliddal, S.; Klose, M. Consequences of undertreatment of hypothyroidism. Endocrine, 2024, 84(2), 301-308.
[http://dx.doi.org/10.1007/s12020-023-03460-1] [PMID: 37556077]
[12]
Cohen, B.; Bental, T.; Perl, L.; Vaknin Assa, H.; Codner, P.; Orvin, K.; Barkan, Y.T.; Levi, A.; Kornowski, R.; Perl, L. Hypothyroidism predicts worsened prognosis in patients undergoing percutaneous coronary intervention. Front. Cardiovasc. Med., 2022, 9, 984952.
[http://dx.doi.org/10.3389/fcvm.2022.984952] [PMID: 36523371]
[13]
Gilani, N.; Wang, K.; Muncan, A.; Peter, J.; An, S.; Bhatti, S.; Pandya, K.; Zhang, Y.; Tang, Y.D.; Gerdes, A.M.; Stout, R.F.; Ojamaa, K. Triiodothyronine maintains cardiac transverse-tubule structure and function. J. Mol. Cell. Cardiol., 2021, 160, 1-14.
[http://dx.doi.org/10.1016/j.yjmcc.2021.06.010] [PMID: 34175303]
[14]
Fliers, E.; Boelen, A. An update on non-thyroidal illness syndrome. J. Endocrinol. Invest., 2021, 44(8), 1597-1607.
[http://dx.doi.org/10.1007/s40618-020-01482-4] [PMID: 33320308]
[15]
Zhou, P.; Huang, LY.; Zhai, M.; Huang, Y.; Zhuang, XF.; Liu, HH.; Zhang, YH.; Zhang, J. Clinical features and prognosis of patients hospitalized with heart failure and low T3 syndrome. Zhonghua Nei Ke Za Zhi, 2023, 62(5), 526-531.
[http://dx.doi.org/10.3760/cma.j.cn112138-20230210-00078]
[16]
Shah, R.; Orlov, S.; Paré, G.; Gerstein, H.C. Thyroid dysfunction and cardiovascular events in patients with dysglycemia. Can. J. Diabetes, 2023, 47(3), 257-262.
[http://dx.doi.org/10.1016/j.jcjd.2023.01.007] [PMID: 36858924]
[17]
Triggiani, V.; Cittadini, A.; Lisco, G. Effect of levothyroxine replacement therapy in patients with subclinical hypothyroidism and chronic heart failure: A systematic review. Front. Endocrinol., 2022, 13, 1013641.
[http://dx.doi.org/10.3389/fendo.2022.1013641] [PMID: 36457560]
[18]
Zhang, X.; Chen, L.; Sheng, J.; Li, C.; He, Y.; Han, W. The association of autoantibodies in hyperthyroid heart disease combined with pulmonary hypertension. Int. J. Endocrinol., 2019, 2019, 1-8.
[http://dx.doi.org/10.1155/2019/9325289] [PMID: 31885565]
[19]
klabunde, RE. Cardiovascular Physiology Concepts; Lippin-cott Williams & Wilkins: Philadelphia, 2011, pp. 41-59.
[20]
Razvi, S.; Jabbar, A.; Pingitore, A.; Danzi, S.; Biondi, B.; Klein, I.; Peeters, R.; Zaman, A.; Iervasi, G. Thyroid hormones and cardiovascular function and diseases. J. Am. Coll. Cardiol., 2018, 71(16), 1781-1796.
[http://dx.doi.org/10.1016/j.jacc.2018.02.045] [PMID: 29673469]
[21]
Diniz, G.P.; Takano, A.P.C.; Bruneto, E.; da Silva, F.G.; Nunes, M.T.; Barreto-Chaves, M.L.M. New insight into the mechanisms associated with the rapid effect of T3 on AT1R expression. J. Mol. Endocrinol., 2012, 49(1), 11-20.
[http://dx.doi.org/10.1530/JME-11-0141] [PMID: 22525353]
[22]
Chen, S.; Wohlford, G.F.; Vecchie’, A.; Carbone, S.; Yavuz, S.; Van Tassell, B.; Abbate, A.; Celi, F.S. Acute effects of liothyronine administration on cardiovascular system and energy metabolism in healthy volunteers. Front. Endocrinol., 2022, 13, 843539.
[http://dx.doi.org/10.3389/fendo.2022.843539] [PMID: 35295986]
[23]
Collet, J.P.; Thiele, H.; Barbato, E.; Barthélémy, O.; Bauersachs, J.; Bhatt, D.L.; Dendale, P.; Dorobantu, M.; Edvardsen, T.; Folliguet, T.; Gale, C.P.; Gilard, M.; Jobs, A.; Jüni, P.; Lambrinou, E.; Lewis, B.S.; Mehilli, J.; Meliga, E.; Merkely, B.; Mueller, C.; Roffi, M.; Rutten, F.H.; Sibbing, D.; Siontis, G.C.M.; Kastrati, A.; Mamas, M.A.; Aboyans, V.; Angiolillo, D.J.; Bueno, H.; Bugiardini, R.; Byrne, R.A.; Castelletti, S.; Chieffo, A.; Cornelissen, V.; Crea, F.; Delgado, V.; Drexel, H.; Gierlotka, M.; Halvorsen, S.; Haugaa, K.H.; Jankowska, E.A.; Katus, H.A.; Kinnaird, T.; Kluin, J.; Kunadian, V.; Landmesser, U.; Leclercq, C.; Lettino, M.; Meinila, L.; Mylotte, D.; Ndrepepa, G.; Omerovic, E.; Pedretti, R.F.E.; Petersen, S.E.; Petronio, A.S.; Pontone, G.; Popescu, B.A.; Potpara, T.; Ray, K.K.; Luciano, F.; Richter, D.J.; Shlyakhto, E.; Simpson, I.A.; Sousa-Uva, M.; Storey, R.F.; Touyz, R.M.; Valgimigli, M.; Vranckx, P.; Yeh, R.W.; Barbato, E.; Barthélémy, O.; Bauersachs, J.; Bhatt, D.L.; Dendale, P.; Dorobantu, M.; Edvardsen, T.; Folliguet, T.; Gale, C.P.; Gilard, M.; Jobs, A.; Jüni, P.; Lambrinou, E.; Lewis, B.S.; Mehilli, J.; Meliga, E.; Merkely, B.; Mueller, C.; Roffi, M.; Rutten, F.H.; Sibbing, D.; Siontis, G.C.M. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J., 2021, 42(14), 1289-1367.
[http://dx.doi.org/10.1093/eurheartj/ehaa575] [PMID: 32860058]
[24]
Whelton, P.K.; Carey, R.M.; Aronow, W.S.; Casey, D.E., Jr; Collins, K.J.; Dennison Himmelfarb, C.; DePalma, S.M.; Gidding, S.; Jamerson, K.A.; Jones, D.W.; MacLaughlin, E.J.; Muntner, P.; Ovbiagele, B.; Smith, S.C., Jr; Spencer, C.C.; Stafford, R.S.; Taler, S.J.; Thomas, R.J.; Williams, K.A., Sr; Williamson, J.D.; Wright, J.T., Jr 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/] ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A Report of the American college of cardiology/american heart association task force on clinical practice guidelines. Hypertension, 2018, 71(6), e13-e115.
[http://dx.doi.org/10.1161/HYP.0000000000000065] [PMID: 29133356]
[25]
Mitchell, C.; Rahko, P.S.; Blauwet, L.A.; Canaday, B.; Finstuen, J.A.; Foster, M.C.; Horton, K.; Ogunyankin, K.O.; Palma, R.A.; Velazquez, E.J. Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: Recommendations from the american society of echocardiography. J. Am. Soc. Echocardiogr., 2019, 32(1), 1-64.
[http://dx.doi.org/10.1016/j.echo.2018.06.004] [PMID: 30282592]
[26]
Panday, P.; Arcia Franchini, A.P.; Iskander, B.; Anwer, F.; Oliveri, F.; Kakargias, F.; Hamid, P. Subclinical hypothyroidism in geriatric population and its association with heart failure. Cureus, 2021, 13(4), e14296.
[http://dx.doi.org/10.7759/cureus.14296] [PMID: 33968510]
[27]
Yuan, D.; Zhang, C.; Jia, S.; Liu, Y.; Jiang, L.; Xu, L.; Zhang, Y.; Xu, J.; Xu, B.; Hui, R.; Gao, R.; Gao, Z.; Song, L.; Yuan, J. Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr. Metab. Cardiovasc. Dis., 2021, 31(2), 579-586.
[http://dx.doi.org/10.1016/j.numecd.2020.10.011] [PMID: 33250369]
[28]
Zhao, X.; Zhang, R.; Jiang, H.; Liu, K.; Ma, C.; Bai, M.; An, T.; Yao, Y.; Wang, X.; Wang, M.; Li, Y.; Zhang, Y.; Zhang, J. Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure. BMC Endocr. Disord., 2021, 21(1), 140.
[http://dx.doi.org/10.1186/s12902-021-00801-x] [PMID: 34215247]
[29]
Pingitore, A.; Landi, P.; Taddei, M.C.; Ripoli, A.; L’Abbate, A.; Iervasi, G. Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am. J. Med., 2005, 118(2), 132-136.
[http://dx.doi.org/10.1016/j.amjmed.2004.07.052] [PMID: 15694896]
[30]
Iervasi, G.; Pingitore, A.; Landi, P.; Raciti, M.; Ripoli, A.; Scarlattini, M.; L’Abbate, A.; Donato, L. Low-T3 syndrome. Circulation, 2003, 107(5), 708-713.
[http://dx.doi.org/10.1161/01.CIR.0000048124.64204.3F] [PMID: 12578873]
[31]
Rahamim, E.; Nachman, D.; Yagel, O.; Yarkoni, M.; Elbaz-Greener, G.; Amir, O.; Asleh, R. Contemporary pillars of heart failure with reduced ejection fraction medical therapy. J. Clin. Med., 2021, 10(19), 4409.
[http://dx.doi.org/10.3390/jcm10194409] [PMID: 34640427]
[32]
Bozkurt, B.; Nair, A.P.; Misra, A.; Scott, C.Z.; Mahar, J.H.; Fedson, S. Neprilysin inhibitors in heart failure. JACC Basic Transl. Sci., 2023, 8(1), 88-105.
[http://dx.doi.org/10.1016/j.jacbts.2022.05.010] [PMID: 36777165]
[33]
Mohamud, M.A.; İbrahim, İ.G.; Ahmed, S.A.; Karataş, M.; Jeele, M.O.O. Prevalence of thyroid dysfunction among patients with heart failure at a tertiary hospital in Mogadishu, Somalia. Int. J. Gen. Med., 2022, 15, 6335-6339.
[http://dx.doi.org/10.2147/IJGM.S371697] [PMID: 35924177]
[34]
Hamilton, M.A.; Stevenson, L.W.; Luu, M.; Walden, J.A. Altered thyroid hormone metabolism in advanced heart failure. J. Am. Coll. Cardiol., 1990, 16(1), 91-95.
[http://dx.doi.org/10.1016/0735-1097(90)90462-X] [PMID: 2358611]
[35]
Opasich, C.; Pacini, F.; Ambrosino, N.; Riccardi, P.G.; Febo, O.; Ferrari, R.; Cobelli, F.; Tavazzi, L. Sick euthyroid syndrome in patients with moderate-to-severe chronic heart failure. Eur. Heart J., 1996, 17(12), 1860-1866.
[http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a014804] [PMID: 8960429]
[36]
Psirropoulos, D.; Lefkos, N.; Boudonas, G.; Efthimiadis, A.; Vogas, V.; Keskilidis, C.; Tsapas, G. Heart failure accompanied by sick euthyroid syndrome and exercise training. Curr. Opin. Cardiol., 2002, 17(3), 266-270.
[http://dx.doi.org/10.1097/00001573-200205000-00009] [PMID: 12015476]
[37]
Kozdag, G.; Ural, D.; Vural, A.; Agacdiken, A.; Kahraman, G.; Sahin, T.; Ural, E.; Komsuoglu, B. Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur. J. Heart Fail., 2005, 7(1), 113-118.
[http://dx.doi.org/10.1016/j.ejheart.2004.04.016] [PMID: 15642542]
[38]
Nägele, M.P.; Barthelmes, J.; Kreysing, L.; Haider, T.; Nebunu, D.; Ruschitzka, F.; Sudano, I.; Flammer, A.J. Endocrine hormone imbalance in heart failure with reduced ejection fraction: A cross‐sectional study. Health Sci. Rep., 2022, 5(6), e880.
[http://dx.doi.org/10.1002/hsr2.880] [PMID: 36320653]
[39]
Liu, C.; Xin, Z.; Hua, L. Lower free triiodothyronine levels are associated with higher all-cause and cardiovascular mortality in people with diabetes-NHANES 2007-2012. Diabetes Res. Clin. Pract., 2023, 202, 110811.
[http://dx.doi.org/10.1016/j.diabres.2023.110811] [PMID: 37391035]
[40]
Sato, Y.; Yoshihisa, A.; Kimishima, Y.; Kiko, T.; Kanno, Y.; Yokokawa, T.; Abe, S.; Misaka, T.; Sato, T.; Oikawa, M.; Kobayashi, A.; Yamaki, T.; Kunii, H.; Nakazato, K.; Takeishi, Y. Low T3 syndrome is associated with high mortality in hospitalized patients with heart failure. J. Card. Fail., 2019, 25(3), 195-203.
[http://dx.doi.org/10.1016/j.cardfail.2019.01.007] [PMID: 30682427]
[41]
Shi, C.; Bao, Y.; Chen, X.; Tian, L. The effectiveness of thyroid hormone replacement therapy on heart failure and low-triiodothyronine syndrome: An updated systematic review and meta-analysis of randomized controlled trials. Endocr. Pract., 2022, 28(11), 1178-1186.
[http://dx.doi.org/10.1016/j.eprac.2022.07.004] [PMID: 35850449]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy