Thyroid Dysfunction and Cardiovascular Risk—— Epidemiological Links, Mechanistic Pathways, and Clinical Management Strategies
Article ID:
4737
Keywords:
Thyroid Dysfunction;Cardiovascular Risk;Epidemiology;Pathophys-iology;Thyroid Hormone Receptor - TRα1/TRβ1;Subclinical Thyroid Disease
Abstract
Abnormal thyroid function (hyperthyroidism/hypothyroidism) significantly increases the risk of cardiovascular disease, and the associations are
population heterogeneous (older age, perimenopause in women, geographic
differences in iodine status). Epidemiologic studies have shown that subclinical
hyperthyroidism increases the risk of atrial fibrillation by 4.5-fold and coronary
events by 3.4-fold, especially in elderly and diabetic patients, and that subclinical hypothyroidism (TSH ≥7 mIU/L) significantly accelerates the progression of
coronary artery calcification (37.6% increase in annualized rate) and is associated with dyslipidemia and pericardial effusions. The core mechanisms involve
thyroid hormone receptor (TRα1/TRβ1)-mediated myocardial remodeling (regulation of genes such as MYH6/7, SERCA2a, and ion channel functions such
as HCN4 and Cx43), metabolic-oxidative stress axis damage (dysregulation of
SREBP-2/LXRs, eNOS uncoupling, and activation of NLRP3 inflammatory
vesicles), and neuroendocrine-hemodynamic interaction modulation (sympathetic overactivation/ANP resistance). Clinical management emphasizes thyroid
function screening (TSH/FT4) in patients with specific cardiovascular diseases
(e.g., heart failure, atrial fibrillation), individualization of treatment regimens for
hyperthyroidism (antithyroid, beta-blockers) and hypothyroidism (levothyroxine
titrated to a TSH of 0.5-2.0 mIU/L), and optimization of cardiovascular outcomes
through multidisciplinary collaborative pathways and long-term monitoring. Future focus needs to be on subclinical disease intervention threshold precision and
development of novel targeted agents (e.g., STRMs).
Published
2025-08-26
Copyright (c) 2025 Danyao Zhang, Yuelei Wu, Haining Xi
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
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[2] Chen Huixin, Zhan Dawei, Feng Baoxiang, et al. Epidemiological study on thyroid diseases in adults in Jilin Province [J]. Chinese Journal of Endemic Disease Prevention and Control, 2017,32 (3):241-244.
[3] Zhang Mengjie, Sun Yu, Wang Yan, et al. Cross-sectional study on thyroid diseases and dyslipidemia in the elderly population in high-iodine areas [J]. Journal of Chongqing Medical University, 2022,47 (11):1305-1309.
[4] Qiao Ruyue and Qin Gang. Advances in the study of the correlation between thyroid-stimulating hormone and cardiovascular diseases in the elderly [J]. Practical Geriatrics, 2023,37 (7):147-152.
[5] McClain A K, Monteleone P P, Zoldan J. Sex in cardiovascular disease: Why this biological variable should be considered in in vitro models [J]. Science Advances, 2024, 10 (20):eadn3510.
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[9]Zaghiraya Zainal, Xing Shuqing, Rengul Aikaber, et al. Current status and characteristics of thyroid diseases in perimenopausal and postmenopausal women [J]. Chinese Journal of General Practice, 2021,24 (3):310-315.
[10] Wu Meiqin, Yan Chonghuai. Advances in the study of animal models of subclinical hypothyroidism [J]. Advances in Animal Medicine, 2019,40 (8):102-105.
[11] Liu Lu. Advances in clinical research on thyroid diseases during pregnancy [J]. Chinese Journal of Endocrinology and Metabolism, online first.
[12] Xu Xiaojin, Geng Jin, Hu Tingting, et al. The effect of subclinical hyperthyroidism on adverse cardiovascular events in patients with type 2 diabetes mellitus [J]. Shandong Pharmaceutical, 2017,57 (14):68-71.
[13] Hu Xiaodong, Li Yushu, Lu Zhaohui. Management of hyperthyroidism in the elderly [J]. Chinese Journal of Practical Internal Medicine, 2021,41 (2):92-95.
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[17] Chen Hailan, Gao Yu. Research progress on hyperthyroidism combined with cardiovascular disease [J]. Chinese Journal of Gerontology, 2016,36 (16):4122-4124.
[18] Liu Wentao, Mi Rui, Yang Rongli. The Correlation of Apolipoprotein E Gene Polymorphism with Uric Acid and Lipid Levels in Elderly Patients with Coronary Heart Disease [J]. Chinese Journal of Geriatric Cardiovascular Diseases, 2024,26 (6):607-610. [19] Peng Xinghua, Li Zhanghong, Li Haiping, et al. The Effects of Scutellarein on Platelet Function, Lipid Levels, and ApoAI and ApoB in Coronary Heart Disease Rats via the Notch Pathway [J]. Chinese Journal of Gerontology, 2024,44 (17):4243-4247.
[20] Cui Xiaoshan, Li Hongzheng, Li Liang, et al. A Network Meta-Analysis on the Effects of Different Traditional Chinese Medicines on Lipid Levels and Microcirculation in Patients with Coronary Heart Disease with Phlegm-Stasis Syndrome [J]. New Traditional Chinese Medicine and Clinical Pharmacology, 2024,35 (7):1069-1083.
[21] Ren Jun, Chen Jinhua. The effect of Haimoibei combined with atorvastatin on improving lipid levels and carotid artery status in elderly patients with coronary heart disease and hyperlipidemia [J]. Chinese Journal of Gerontology, 2025,45 (9):2061-2064.
[22] Wang Yundan, Ye Sufang, Shen Jianying. Correlation analysis of arrhythmia and blood uric acid and estrogen levels in perimenopausal women [J]. Chinese Journal of Maternal and Child Health Care, 2024,39 (10):1903-1906.
[23] Wang S, [23] Wang S, et al. Cesarean delivery and blood DNA methylation at birth: A meta-analysis[J]. Sci Adv, 2024, 10(47):eadr2084.
[24] Li X, [24] Li X, et al. Genetic variants associated with thyroid dysfunction and cardiovascular risk[J]. Sci Adv, 2023, 9(36):adj9797.
[25] Zhang Y, [25] Zhang Y, et al. Regional differences in hypothyroidism-induced coronary artery disease: An epidemiological study[J]. Sci Adv, 2022, 8(41):ads6947.
[26] Liu Z, [26] Liu Z, et al. Inflammation and thyroid function in cardiovascular disease: A mechanistic analysis[J]. Science Advances, 2021, 7(23):abf5013.
[27]Lohry D P, Stevens T A, Shen T, [27]Lohry D P, Stevens T A, Shen T, et al.Hormone response elements for the thyroid receptor-α include specific distal 5′-flanking DNA.Science Advances, 2024, 10(47): eadr1033. DOI: 10.1126/sciadv.adr1033.
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[30]Affortit C, Blanc F, Nasr J, et al. Disease-related mutations of the thyroid hormone receptor α1 cause hearing loss and sensory hair cell pattern defects in mice. Science Signaling, 2022,15(734): eabj4583. DOI: 10.1126/scisignal.abj4583.
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[32]Chua N K, Coates H W, Brown A J.Cholesterol, cancer, and rebooting a treatment for athlete's foot[J].Science Translational Medicine, 2018, 10(438): eaat3741. DOI: 10.1126/scitranslmed.aat3741.
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[34]Xu B, Lawler K, Wyler S, et al. Orthopaedic Regulation of Melanocyte-4 Receptor Transcript and Energy Homeostasis. Science Translational Medicine, 2025,17: eadr6459. DOI: 10.1126/scitranslmed.adr6459.
[35]Romero J A, Axelrod J. Diurnal variation in sensitivity of pineal β-adrenergic receptors. Science, 1974,184 (4141):1091-1092.
[36]Cao Y, Wang Y, Zhou Z, et al. Liver heart interaction mediated by coagulation factor XI protects the heart from failure. Science, 2022,377:1399-1406. DOI: 10.1126/science.abn0910.
[37]Abdellatif M, Trummer-Herbst V, Koser F, et al. Nicotinamide therapy for heart failure with preserved ejection fraction. Science Translational Medicine, 2021,13: eabd7064. DOI: 10.1126/scitranslmed.abd7064.
[38]Nyns E C A, Poelma R H, Volkers L, et al. An automated hybrid bioelectronic system for the spontaneous recovery of sinus rhythm in atrial fibrillation. Science Translational Medicine, 2019,11: eaau6447. DOI: 10.1126/scitranslmed.aau6447.
[39] Yu Z, Zekavat S M, Haidermota S, et al. A genome-wide pleiotropy analysis of coronary artery disease and pneumonia identifies shared immune pathways. Science Advances, 2022,8: eabl4602. DOI: 10.1126/sciadv.abl4602.
[40]Zhao P, Yao Q, Zhang P J, et al. Single-cell RNA sequencing reveals the key role of novel pro-inflammatory endothelial-mesenchymal transition in adverse coronary artery remodeling. Science Advances, 2021,7(34): eabg1694. DOI: 10.1126/sciadv.abg1694.
[41]Arunachalam P S, Wimmers F, Mok C K P, et al. Systems Biology Assessment of Immune Responses in Human Mild and Severe COVID-19 Infections. Science, 2020,369 (6508):1210-1220. DOI: 10.1126/science.abc6261.
[42]Oliveras-Canellas N., Castells-Nobau A., de la Vega-Correa L., et al. Fat tissue co-regulates cognitive function. Science Advances, 2023,9(33): eadg4017. DOI: 10.1126/sciadv.adg4017.
[43]Xu X, Cao S, Hübner H, et al. Adaptive cognitive control circuit changes associated with problem-solving ability and depression symptom outcomes over 24 months[J]. Science Translational Medicine, 2024, 16(734): eadh3172.
[44]Brown G E, Han Y D, Michell A R, [44]Brown G E, Han Y D, Michell A R, et al. Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation[J]. Science Advances, 2024, 10(3): eadg1222.
[45]Xu J, Cao S, Hübner H, et al. Structural insights into ligand recognition, activation, and signaling of the α₂A adrenergic receptor[J]. Science Advances, 2022, 8(10): eabj5347.
[46]Morshed S A, Ma R, Latif R, [46]Morshed S A, Ma R, Latif R, et al. Biased signaling by thyroid-stimulating hormone receptor-specific antibodies determines thyrocyte survival in autoimmunity[J]. Science Signaling, 2018, 11(514): eaah4120.
[47]Reker D, Blum S M, Steiger C, et al. "Inactive" ingredients in oral medications[J]. Science Translational Medicine, 2019, 11(483): eaau6753.
[48]Lam C G, Howard S C, Bouffet E, [48]Lam C G, Howard S C, Bouffet E, et al. Science and health for all children with cancer[J]. Science, 2019, 363(6430): 1182-1186.
[49]Lechner M G, Zhou Z, Hoang A T, [49]Lechner M G, Zhou Z, Hoang A T, et al. Clonally expanded, thyrotoxic effector CD8+ T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis[J]. Science Translational Medicine, 2023, 15(737): eadg0675.
[50]Leone P, Shera D, McPhee S W J, [50]Leone P, Shera D, McPhee S W J, et al. Long-Term Follow-Up After Gene Therapy for Canavan Disease[J]. Science Translational Medicine, 2012, 4(165): 165ra163.
