Subclinical Hypothyroidism - What is Responsible for its Association with Cardiovascular Disease?

Abstract

Subclinical hypothyroidism (SH) is a common condition, with prevalence estimates ranging from 4-20%, depending on the population demographics. Although epidemiological analysis associates it with an increased risk of cardiovascular disease, clinical practice guidelines express uncertainty about whether to monitor or to treat. As we await large-scale, well-designed randomised clinical trials regarding treatment of SH, a review of pathophysiological considerations may be informative to better understand this disorder.

Keywords: Subclinical hypothyroidism; adipocytes; cardiovascular disease; cholesterol; endothelial cells; inflammation; thyroid-stimulating hormone; vascular smooth muscle cells.

Figure 1:. Subclinical hypothyroidism and cardiovascular disease

CVD = cardiovascular disease; SH = subclinical hypothyroidism; TSH = thyroid-simulating hormone. Depiction of potential pathways through which the extra-thyroidal effects of elevated thyroid-stimulating hormone (TSH) levels might lead to cardiovascular disease (CVD). TSH-induced dysfunction of adipocytes may lead to release of adipokines that directly act on the vasculature, or indirectly act through activation of monocytes and/or platelets. TSH-stimulated disruption of vascular smooth muscle cells and endothelial cells may also promote CVD. Please refer to the text for details, as well as for discussion of other atherogenic processes associated with subclinical hypothyroidism, such as dyslipidemia.