Correlation Study Between Subclinical Hypothyroidism and Coronary Atherosclerotic Heart Disease
Keywords:
coronary heart disease, subclinical hypothyroidism, atherosclerosis, thyroid hormone replacement therapy
Abstract
Subclinical hypothyroidism (SCH) is recognized as a potential independent risk factor for coronary artery disease (CAD). This review systematically explores the association between SCH and CAD, examining mechanisms including atherogenesis, inflammatory responses, and interactions with traditional CAD risk factors. We found that varying TSH levels, sex, and the presence of comorbidities in patients with SCH are associated with the development and progression of CAD, though the underlying mechanisms remain unclear. While thyroid hormone replacement therapy can improve lipid profiles and endothelial function, the cardiovascular benefits regarding hard endpoints in patients with mild SCH (TSH<10 mIU/L) or in elderly populations require confirmation through large randomized controlled trials (RCTs). In conclusion, the association between SCH and CAD is multifactorial and synergistic, and clinical intervention should consider individualized TSH levels, age, and the presence of comorbidities.
References
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[7] Gill, S., Cheed, V., Morton, V. A. H., et al. (2022). Evaluating the Progression to Hypothyroidism in Preconception Euthyroid Thyroid Peroxidase Antibody-Positive Women. Journal of Clinical Endocrinology & Metabolism, 108(1), 124–134. https://doi.org/10.1210/clinem/dgac525
[8] Patrizio, A., Ferrari, S. M., Elia, G., et al. (2024). Hypothyroidism and metabolic cardiovascular disease. Frontiers in Endocrinology, 15, 1408684. https://doi.org/10.3389/fendo.2024.1408684
[9] Cappola, A. R., Desai, A. S., Medici, M., et al. (2019). Thyroid and cardiovascular disease: Research agenda for enhancing knowledge, prevention, and treatment. Circulation, 29(6), 760–777. https://doi.org/10.1161/CIRCULATIONAHA.118.036859
[10] Swirski, F. K., & Nahrendorf, M. (2013). Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science, 339(6116), 161–166. https://doi.org/10.1126/science.1230719
[11] Johnson, J. L., & Newby, A. C. (2009). Macrophage heterogeneity in atherosclerotic plaques. Current Opinion in Lipidology, 20(5), 370–378. https://doi.org/10.1097/MOL.0b013e3283309848
[12] Yang, C., Lu, M., Chen, W., et al. (2019). Thyrotropin aggravates atherosclerosis by promoting macrophage inflammation in plaques. Journal of Experimental Medicine, 216(5), 1182–1198. https://doi.org/10.1084/jem.20181473
[13] Ohba, K., & Iwaki, T. (2022). Role of thyroid hormone in an experimental model of atherosclerosis: The potential mediating role of immune response and autophagy. Endocrine Journal, 69(9), 1043–1052. https://doi.org/10.1507/endocrj.EJ22-0177
[14] Torres, E. M., & Tellechea, M. L. (2025). Systematic review and meta-analyses of adipokine levels in hypothyroidism: A role for retinol-binding protein 4. Expert Review of Endocrinology & Metabolism, 20(1), 87–98. https://doi.org/10.1080/17446651.2024.2438231
[15] Elkholy, A., Efat, A., Shoeib, S., et al. (2025). Platelet indices and RDW to assess inflammatory milieu in subclinical hashimoto's thyroiditis. Clinical Medicine Insights: Endocrinology and Diabetes, 18, 11795514251349337. https://doi.org/10.1177/11795514251349337
[16] Medina-Leyte, D. J., Zepeda-García, O., Domínguez-Pérez, M., et al. (2021). Endothelial dysfunction, inflammation and coronary artery disease: Potential biomarkers and promising therapeutical approaches. International Journal of Molecular Sciences, 22(8), 3850. https://doi.org/10.3390/ijms22083850
[17] Traub-Weidinger, T., Graf, S., Beheshti, M., et al. (2012). Coronary vasoreactivity in subjects with thyroid autoimmunity and subclinical hypothyroidism before and after supplementation with thyroxine. Thyroid, 22(3), 245–251. https://doi.org/10.1089/thy.2011.0183
[18] Knapp, M., Lisowska, A., Sobkowicz, B., et al. (2013). Myocardial perfusion and intima-media thickness in patients with subclinical hypothyroidism. Advances in Medical Sciences, 58(1), 44–49. https://doi.org/10.2478/v10039-012-0068-9
[19] Sara, J. D., Zhang, M., Gharib, H., et al. (2015). Hypothyroidism is associated with coronary endothelial dysfunction in women. Journal of the American Heart Association, 4(8), e002225. https://doi.org/10.1161/JAHA.115.002225
[20] Obradovic, M., Gluvic, Z., Sudar-Milovanovic, E., et al. (2016). Nitric oxide as a marker for levo-thyroxine therapy in subclinical hypothyroid patients. Current Vascular Pharmacology, 14(3), 266–270. https://doi.org/10.2174/1570161114666160208143537
[21] Viswanathan, G., Balasubramaniam, K., Hardy, R., et al. (2014). Blood thrombogenicity is independently associated with serum TSH levels in post-non-ST elevation acute coronary syndrome. Journal of Clinical Endocrinology and Metabolism, 99(6), E1050–E1054. https://doi.org/10.1210/jc.2013-3062
[22] Guo, W., Hou, L. Y., & Yi, X. (2025). Impact of subclinical hypothyroidism on coagulation parameters and coronary artery disease severity in patients with coronary heart disease. Cardiology, 1, 1–11. https://doi.org/10.1159/000545904
[23] Bytyçi, I., Shenouda, R., Wester, P., et al. (2021). Carotid atherosclerosis in predicting coronary artery disease: A systematic review and meta-analysis. Arteriosclerosis, Thrombosis, and Vascular Biology, 41(4). https://doi.org/10.1161/ATVBAHA.120.315747
[24] Polak, J. F., Szklo, M., & O'Leary, D. H. (2017). Carotid intima-media thickness score, positive coronary artery calcium score, and incident coronary heart disease: The multi-ethnic study of atherosclerosis. Journal of the American Heart Association, 6(1), e004612. https://doi.org/10.1161/JAHA.116.004612
[25] Soto-García, A. J., Elizondo-Riojas, G., Rodriguez-Gutiérrez, R., et al. (2021). Carotid intima-media thickness in patients with subclinical hypothyroidism: A prospective controlled study. Clinical and Investigative Medicine, 44(4), E39–E45. https://doi.org/10.25011/cim.v44i4.37139
[26] Koc, A. (2023). Evaluation of the association of plasma pentraxin-3 levels with carotid intima-media thickness and high-sensitive CRP in patients with subclinical hypothyroidism. Acta Endocrinologica (Bucharest), 19(3), 286–291. https://doi.org/10.4183/aeb.2023.286
[27] Isailă, O. M., Stoian, V. E., Fulga, I., et al. (2024). The relationship between subclinical hypothyroidism and carotid intima-media thickness as a potential marker of cardiovascular risk: A systematic review and a meta-analysis. Journal of Cardiovascular Development and Disease, 11(4), 98. https://doi.org/10.3390/jcdd11040098
[28] Spilack, A. D. M., Goulart, A. C., De Almeida-Pititto, B., et al. (2023). The association of diabetes, subclinical hypothyroidism and carotid intima-media thickness: Results from the brazilian longitudinal study of adult health (ELSA-brazil). Clinics, 78, 100154. https://doi.org/10.1016/j.clinsp.2022.100154
[29] Cabral, M. D., Teixeira, P. F. S., Silva, N. A. O., et al. (2009). Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism. Brazilian Journal of Medical and Biological Research, 42(5), 426–432. https://doi.org/10.1590/S0100-879X2009000500005
[30] Posadas-Romero, C., Jorge-Galarza, E., Posadas-Sánchez, R., et al. (2014). Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis. European Journal of Endocrinology, 171(3), 319–325. https://doi.org/10.1530/EJE-14-0150
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