Hypothyroidism and Risk of Cardiovascular Disease

Abstract

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 andfunction and impaired blood and oxygen supply induced by accelerated atherosclerosis. The increased risk ofacceleration 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. Instabilityof atherosclerotic plaque in hypothyroidism could cause excessive activity of the elements of innateimmunity, which are characterized by the significant presence of macrophages in atherosclerotic plaques, increasednuclear factor kappa B (NFkB) expression, and elevated levels of tumor necrosis factor α (TNF-α) andmatrix metalloproteinase (MMP) 9, with reduced interstitial collagen; all of them together creates inflammationmilieu, resulting in plaque rupture. Optimal substitution by levothyroxine (LT4) restores biochemical euthyroidism.In postmenopausal women and elderly patients with hypothyroidism and associated vascularcomorbidity, excessive LT4 substitution could lead to atrial rhythm disorders and osteoporosis. Therefore, it isof interest to maintain thyroid-stimulating hormone (TSH) levels in the reference range, thus eliminating thedeleterious effects of lower or higher TSH levels on the cardiovascular system. This review summarizes the recentliterature on subclinical and clinical hypothyroidism and atherosclerotic cardiovascular disease and discussesthe effects of LT4 replacement therapy on restoring biochemical euthyroidism and atherosclerosis processes.