The impact of thyroid hormone dysfunction on ischemic heart disease

Abstract

Thyroid hormones have a central role in cardiovascular homeostasis. In myocardium, these hormones stimulate both diastolic myocardial relaxation and systolic myocardial contraction, have a pro-angiogenic effect and an important role in extracellular matrix maintenance. Thyroid hormones modulate cardiac mitochondrial function. Dysfunction of thyroid axis impairs myocardial bioenergetic status. Both overt and subclinical hypothyroidism are associated with a higher incidence of coronary events and an increased risk of heart failure progression. Endothelial function is also impaired in hypothyroid state, with decreased nitric oxide-mediated vascular relaxation. In heart disease, particularly in ischemic heart disease, abnormalities in thyroid hormone levels are common and are an important factor to be considered. In fact, low thyroid hormone levels should be interpreted as a cardiovascular risk factor. Regarding ischemic heart disease, during the late post-myocardial infarction period, thyroid hormones modulate left ventricular structure, function and geometry. Dysfunction of thyroid axis might even be more prevalent in the referred condition since there is an upregulation of type 3 deiodinase in myocardium, producing a state of local cardiac hypothyroidism. In this focused review, we summarize the central pathophysiological and clinical links between altered thyroid function and ischemic heart disease. Finally, we highlight the potential benefits of thyroid hormone supplementation as a therapeutic target in ischemic heart disease.

Keywords: hyperthyroidism; hypothyroidism; ischemia/reperfusion injury; ischemic heart disease; mitochondria; thyroid hormones.

Figure 1

Thyroid axis and changes in nonthyroidal illness. Direction of arrows (↑, ↓) indicates increase or decrease, respectively. rT3, reverse triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone.

Figure 2

Main changes in cardiovascular system with low T3 levels in nonthyroidal illness. LDL, low-density lipoprotein; LV, left ventricle; MHC, myosin heavy chain; MMP-2, matrix metalloproteinase-2; NO, nitric oxide; SERCA2, sarcoplasmic/endoplasmic reticulum calcium ATPase 2.