Hypothyroidism and Risk of Cardiovascular Disease

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.