Department of Endocrinology and Diabetes, Clinic for Internal Medicine, Zemun Clinical Hospital, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Curr Pharm Des. 2022;28(25):2065-2072. doi: 10.2174/1381612828666220620160516.
Thyroid hormones (TH) have a significant impact on cellular oxidative metabolism. Besides that, they maintain vascular homeostasis by positive effects on endothelial and vascular smooth muscle cells. Subclinical (SCH) and clinical (CH) hypothyroidism influences target organs by changing their morphology and function and impaired blood and oxygen supply induced by accelerated atherosclerosis. The increased risk of acceleration and extension of atherosclerosis in patients with SCH and CH could be explained by dyslipidemia, diastolic hypertension, increased arterial stiffness, endothelial dysfunction, and altered blood coagulation. Instability of atherosclerotic plaque in hypothyroidism could cause excessive activity of the elements of innate immunity, which are characterized by the significant presence of macrophages in atherosclerotic plaques, increased nuclear factor kappa B (NFkB) expression, and elevated levels of tumor necrosis factor α (TNF-α) and matrix metalloproteinase (MMP) 9, with reduced interstitial collagen; all of them together creates inflammation milieu, resulting in plaque rupture. Optimal substitution by levothyroxine (LT4) restores biochemical euthyroidism. In postmenopausal women and elderly patients with hypothyroidism and associated vascular comorbidity, excessive LT4 substitution could lead to atrial rhythm disorders and osteoporosis. Therefore, it is of interest to maintain thyroid-stimulating hormone (TSH) levels in the reference range, thus eliminating the deleterious effects of lower or higher TSH levels on the cardiovascular system. This review summarizes the recent literature on subclinical and clinical hypothyroidism and atherosclerotic cardiovascular disease and discusses the effects of LT4 replacement therapy on restoring biochemical euthyroidism and atherosclerosis processes.
甲状腺激素 (TH) 对细胞氧化代谢有重要影响。此外，它们通过对内皮细胞和血管平滑肌细胞的积极作用维持血管内稳态。亚临床 (SCH) 和临床 (CH) 甲状腺功能减退症通过改变靶器官的形态和功能以及加速动脉粥样硬化引起的血液和氧气供应受损来影响靶器官。SCH 和 CH 患者的动脉粥样硬化加速和扩展风险增加可以通过血脂异常、舒张期高血压、动脉僵硬增加、内皮功能障碍和凝血改变来解释。甲状腺功能减退症中动脉粥样硬化斑块的不稳定性可能导致固有免疫元素的过度活跃，其特征是斑块中存在大量巨噬细胞、核因子 kappa B (NFkB) 表达增加以及肿瘤坏死因子 α (TNF-α) 和基质金属蛋白酶 (MMP) 9 水平升高，同时间质胶原减少；所有这些共同构成炎症环境，导致斑块破裂。左甲状腺素 (LT4) 的最佳替代可恢复生化甲状腺功能正常。在甲状腺功能减退症和相关血管合并症的绝经后妇女和老年患者中，过量 LT4 替代可能导致心房节律障碍和骨质疏松症。因此，维持促甲状腺激素 (TSH) 水平在参考范围内以消除较低或较高 TSH 水平对心血管系统的有害影响是很有意义的。本综述总结了最近关于亚临床和临床甲状腺功能减退症与动脉粥样硬化性心血管疾病的文献，并讨论了 LT4 替代治疗对恢复生化甲状腺功能正常和动脉粥样硬化过程的影响。
