Abstract
Purpose
Thyroid dysfunction contributes to adverse events in several types of cardiovascular diseases. The aim of the present study is to determine whether thyroid status is associated with the prognosis of patients with acute myocardial infarction (AMI).
Methods
The present cohort arose from the China PEACE‑Prospective AMI study. Based on the evaluation of thyroid status, participants were divided into euthyroid, hypothyroid, and hyperthyroid groups. A total of 2569 AMI patients met the inclusion criteria of our present study. The primary outcomes were the 12-month composite cardiovascular endpoint (CCVE, a composite of all-cause death, myocardial infarction, revascularization, and heart failure) and the composite cardio-cerebral vascular endpoint (CCCVE, comprising CCVE and stroke).
Results
Of the entire cohort, 431 patients (16.8%) confirmed hypothyroid status and 102 (4.0%) were at hyperthyroid status. There were total 594 CCVEs (23.1%) and 687 CCCVEs (26.7%) in the general population. After adjusting conventional risk factors, AMI patients from the hypothyroid status group were at increased risk of the two composite endpoints, compared with euthyroid individuals (CCVE, HR:1.337, 95%CI: 1.097–1.630; CCCVE, HR:1.336, 95%CI: 1.111–1.607). However, no significant increased trends of the two composite endpoints could be observed in hyperthyroid group. Furthermore, hypothyroid status was also independently associated with a higher risk of revascularization (HR: 1.648, 95%CI: 1.047–2.595) and heart failure (HR: 1.382, 95%CI: 1.066–1.792).
Conclusion
Compared with euthyroid status, hypothyroid status has an independent predicting value for adverse cardiovascular events in AMI patients. Further investigations are required to illustrate whether treatment of thyroid dysfunction could improve the prognosis of AMI patients.
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References
E. Puymirat, A. Battler, J. Birkhead, H. Bueno, P. Clemmensen, Y. Cottin, K.A. Fox, B. Gorenek, C. Hamm, K. Huber, M. Lettino, B. Lindahl, C. Muller, A. Parkhomenko, S. Price, T. Quinn, F. Schiele, M. Simoons, G. Tatu-Chitoiu, M. Tubaro, C. Vrints, D. Zahger, U. Zeymer, N. Danchin; participants EHSs, Euro Heart Survey 2009 Snapshot: regional variations in presentation and management of patients with AMI in 47 countries. Eur. Heart J. Acute Cardiovasc. Care 2(4), 359–370 (2013). https://doi.org/10.1177/2048872613497341
J. Li, X. Li, Q. Wang, S. Hu, Y. Wang, F.A. Masoudi, J.A. Spertus, H.M. Krumholz, L. Jiang, ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis of hospital data. Lancet 385(9966), 441–451 (2015). https://doi.org/10.1016/s0140-6736(14)60921-1
J. Ejerhed, H. Nordenstedt, A.C. Laska, International comparisons of acute myocardial infarction. Lancet 384(9940), 303–304 (2014). https://doi.org/10.1016/S0140-6736(14)61234-4
Y.F. Chen, R.A. Redetzke, S. Said, A.J. Beyer, A.M. Gerdes, Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats. Am. J. Physiol. Heart Circ. Physiol. 298(1), H259–262 (2010). https://doi.org/10.1152/ajpheart.00755.2009
A. Bielecka-Dabrowa, B. Godoy, T. Suzuki, M. Banach, S. von Haehling, Subclinical hypothyroidism and the development of heart failure: an overview of risk and effects on cardiac function. Clin. Res. Cardiol. 108(3), 225–233 (2019). https://doi.org/10.1007/s00392-018-1340-1
I. Mourouzis, I. Giagourta, G. Galanopoulos, P. Mantzouratou, E. Kostakou, A.D. Kokkinos, N. Tentolouris, C. Pantos, Thyroid hormone improves the mechanical performance of the post-infarcted diabetic myocardium: a response associated with up-regulation of Akt/mTOR and AMPK activation. Metabolism 62(10), 1387–1393 (2013). https://doi.org/10.1016/j.metabol.2013.05.008
A.L. de Castro, A.V. Tavares, C. Campos, R.O. Fernandes, R. Siqueira, A. Conzatti, A.M. Bicca, T.R. Fernandes, C.L. Sartorio, P.C. Schenkel, A. Bello-Klein, A.S. da Rosa Araujo, Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction. Mol. Cell Endocrinol. 391(1-2), 22–29 (2014). https://doi.org/10.1016/j.mce.2014.04.010
C. Pantos, I. Mourouzis, T. Saranteas, G. Clave, H. Ligeret, P. Noack-Fraissignes, P.Y. Renard, M. Massonneau, P. Perimenis, D. Spanou, G. Kostopanagiotou, D.V. Cokkinos, 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(1), 69–77 (2009). https://doi.org/10.1007/s00395-008-0758-4
L. Friberg, S. Werner, G. Eggertsen, S. Ahnve, Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina? Arch. Intern. Med. 162(12), 1388–1394 (2002)
I. Lymvaios, I. Mourouzis, D.V. Cokkinos, M.A. Dimopoulos, S.T. Toumanidis, C. Pantos, Thyroid hormone and recovery of cardiac function in patients with acute myocardial infarction: a strong association? Eur. J. Endocrinol. 165(1), 107–114 (2011). https://doi.org/10.1530/eje-11-0062
W.Y. Wang, Y.D. Tang, M. Yang, C. Cui, M. Mu, J. Qian, Y.J. Yang, Free triiodothyronine level indicates the degree of myocardial injury in patients with acute ST-elevation myocardial infarction. Chin. Med. J. 126(20), 3926–3929 (2013)
L. Friberg, V. Drvota, A.H. Bjelak, G. Eggertsen, S. Ahnve, Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am. J. Med. 111(9), 699–703 (2001)
S. Satar, G. Seydaoglu, A. Avci, A. Sebe, O. Karcioglu, M. Topal, Prognostic value of thyroid hormone levels in acute myocardial infarction: just an epiphenomenon? Am. Heart Hosp. J. 3(4), 227–233 (2005)
B. Zhang, W. Peng, C. Wang, W. Li, Y. Xu, A low fT3 level as a prognostic marker in patients with acute myocardial infarctions. Intern. Med. 51(21), 3009–3015 (2012). https://doi.org/10.2169/internalmedicine.51.7902
J. Li, R.P. Dreyer, X. Li, X. Du, N.S. Downing, L. Li, H.B. Zhang, F. Feng, W.C. Guan, X. Xu, S.X. Li, Z.Q. Lin, F.A. Masoudi, J.A. Spertus, H.M. Krumholz, L.X. Jiang; China PCG, China patient-centered evaluative assessment of cardiac events prospective study of acute myocardial infarction: study design. Chin. Med J. 129(1), 72–80 (2016). https://doi.org/10.4103/0366-6999.172596
E. von Elm, D.G. Altman, M. Egger, S.J. Pocock, P.C. Gotzsche, J.P. Vandenbroucke; Initiative S, The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596), 1453–1457 (2007). https://doi.org/10.1016/S0140-6736(07)61602-X
M.I. Surks, I.J. Chopra, C.N. Mariash, J.T. Nicoloff, D.H. Solomon, American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 263(11), 1529–1532 (1990)
J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber; American Association Of Clinical E, American Thyroid Association Taskforce On Hypothyroidism In A, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid 22(12), 1200–1235 (2012). https://doi.org/10.1089/thy.2012.0205
L.P. Fried, N.O. Borhani, P. Enright, C.D. Furberg, J.M. Gardin, R.A. Kronmal, L.H. Kuller, T.A. Manolio, M.B. Mittelmark, A. Newman et al. The cardiovascular health study: design and rationale. Ann. Epidemiol. 1(3), 263–276 (1991)
S.S. Martin, N. Daya, P.L. Lutsey, K. Matsushita, A. Fretz, J.W. McEvoy, R.S. Blumenthal, J. Coresh, P. Greenland, A. Kottgen, E. Selvin, Thyroid function, cardiovascular risk factors, and incident atherosclerotic cardiovascular disease: the atherosclerosis risk in communities (ARIC) study. J. Clin. Endocrinol. Metab. 102(9), 3306–3315 (2017). https://doi.org/10.1210/jc.2017-00986
C. Selmer, J.B. Olesen, M.L. Hansen, L.M. von Kappelgaard, J.C. Madsen, P.R. Hansen, O.D. Pedersen, J. Faber, C. Torp-Pedersen, G.H. Gislason, Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J. Clin. Endocrinol. Metab. 99(7), 2372–2382 (2014). https://doi.org/10.1210/jc.2013-4184
M. Imaizumi, M. Akahoshi, S. Ichimaru, E. Nakashima, A. Hida, M. Soda, T. Usa, K. Ashizawa, N. Yokoyama, R. Maeda, S. Nagataki, K. Eguchi, Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J. Clin. Endocrinol. Metab. 89(7), 3365–3370 (2004). https://doi.org/10.1210/jc.2003-031089
M.F. Bai, C.Y. Gao, C.K. Yang, X.P. Wang, J. Liu, D.T. Qi, Y. Zhang, P.Y. Hao, M.W. Li, Effects of thyroid dysfunction on the severity of coronary artery lesions and its prognosis. J. Cardiol. 64(6), 496–500 (2014). https://doi.org/10.1016/j.jjcc.2014.03.009
Zhang K., Meng X., Wang W., Zheng J., An S., Wang S., Qi Y., Gao C., Tang Y.D. Prognostic value of free triiodothyronine level in patients with hypertrophic obstruction cardiomyopathy. J. Clin. Endocrinol. Metab. (2018). 10.1210/jc.2017-02386
G. Iervasi, S. Molinaro, P. Landi, M.C. Taddei, E. Galli, F. Mariani, A. L’Abbate, A. Pingitore, Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch. Intern. Med. 167(14), 1526–1532 (2007). https://doi.org/10.1001/archinte.167.14.1526
N. Rodondi, W.P. den Elzen, D.C. Bauer, A.R. Cappola, S. Razvi, J.P. Walsh, B.O. Asvold, G. Iervasi, M. Imaizumi, T.H. Collet, A. Bremner, P. Maisonneuve, J.A. Sgarbi, K.T. Khaw, M.P. Vanderpump, A.B. Newman, J. Cornuz, J.A. Franklyn, R.G. Westendorp, E. Vittinghoff, J. Gussekloo; Thyroid Studies C, Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 304(12), 1365–1374 (2010). https://doi.org/10.1001/jama.2010.1361
J.P. Walsh, A.P. Bremner, M.K. Bulsara, P. O’Leary, P.J. Leedman, P. Feddema, V. Michelangeli, Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch. Intern. Med. 165(21), 2467–2472 (2005). https://doi.org/10.1001/archinte.165.21.2467
N. Rodondi, A.B. Newman, E. Vittinghoff, N. de Rekeneire, S. Satterfield, T.B. Harris, D.C. Bauer, Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch. Intern. Med. 165(21), 2460–2466 (2005). https://doi.org/10.1001/archinte.165.21.2460
B. Gencer, T.H. Collet, V. Virgini, D.C. Bauer, J. Gussekloo, A.R. Cappola, D. Nanchen, W.P. den Elzen, P. Balmer, R.N. Luben, M. Iacoviello, V. Triggiani, J. Cornuz, A.B. Newman, K.T. Khaw, J.W. Jukema, R.G. Westendorp, E. Vittinghoff, D. Aujesky, N. Rodondi; Thyroid Studies C, Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation 126(9), 1040–1049 (2012). https://doi.org/10.1161/CIRCULATIONAHA.112.096024
D. Nanchen, J. Gussekloo, R.G. Westendorp, D.J. Stott, J.W. Jukema, S. Trompet, I. Ford, P. Welsh, N. Sattar, P.W. Macfarlane, S.P. Mooijaart, N. Rodondi, A.J. de Craen; Group P, Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J. Clin. Endocrinol. Metab. 97(3), 852–861 (2012). https://doi.org/10.1210/jc.2011-1978
T.H. Collet, J. Gussekloo, D.C. Bauer, W.P. den Elzen, A.R. Cappola, P. Balmer, G. Iervasi, B.O. Asvold, J.A. Sgarbi, H. Volzke, B. Gencer, R.M. Maciel, S. Molinaro, A. Bremner, R.N. Luben, P. Maisonneuve, J. Cornuz, A.B. Newman, K.T. Khaw, R.G. Westendorp, J.A. Franklyn, E. Vittinghoff, J.P. Walsh, N. Rodondi; Thyroid Studies C, Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch. Intern Med 172(10), 799–809 (2012). https://doi.org/10.1001/archinternmed.2012.402
Y.D. Tang, J.A. Kuzman, S. Said, B.E. Anderson, X. Wang, A.M. Gerdes, Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction. Circulation 112(20), 3122–3130 (2005). https://doi.org/10.1161/CIRCULATIONAHA.105.572883
A.R. Cappola, P.W. Ladenson, Hypothyroidism and atherosclerosis. J. Clin. Endocrinol. Metab. 88(6), 2438–2444 (2003). https://doi.org/10.1210/jc.2003-030398
S. Stabouli, S. Papakatsika, V. Kotsis, Hypothyroidism and hypertension. Expert Rev. Cardiovasc. Ther. 8(11), 1559–1565 (2010). https://doi.org/10.1586/erc.10.141
Acknowledgements
The authors appreciate the investigators of China PEACE prospective AMI study. We are deeply grateful for the guidance given by Dr. Xi Li and Prof. Jing Li. We acknowledge the help from Wei Li, Yang Wang, and Yanyan Zhao (Medical Research & Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Disease, China) with the statistical analyses.
Funding
This work was supported by National Key Research and Development Program of China (2020YFC2004700), National Natural Science Foundation of China (81800327, 81825003, 91957123), and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2016-I2M-1-009).
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All authors—W.W., S.W., K.Z., J.C., X.Z., C.S., P.L., and Y.D.T.—provided inputs in study design. W.W., S.W., K.Z., J.C., and X.Z. were involved in data collection and data analysis. Y.D.T., W.W., and S.W. were responsible for publication writing. All authors reviewed and approved the final version of this manuscript.
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The China PEACE‑Prospective AMI study was registered on www. clinicaltrials.gov (No. NCT01624909; June 21, 2012).
These authors contributed equally: Wenyao Wang, Siyuan Wang
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Wang, W., Wang, S., Zhang, K. et al. Hypothyroidism is associated with clinical outcomes in patients with acute myocardial infarction: subgroup analysis of China PEACE study. Endocrine 74, 128–137 (2021). https://doi.org/10.1007/s12020-021-02742-w
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DOI: https://doi.org/10.1007/s12020-021-02742-w