Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence

Abstract

It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.

The Role of Hormones in Hidradenitis Suppurativa: A Systematic Review

“…In general, two hormones have an increasing effect on energy metabolism. Thyroid hormones affect the heart by increasing expression of β-receptors and heart rate [ 69 ]. In metabolism, they increase basal metabolic rate and oxygen consumption.…”

Thyroid-stimulating hormone within the normal reference range has a U-shaped association with the severity of coronary artery disease in nondiabetic patients but is diluted in diabetic patients

“…risk of CAD events or CAD mortality. [5][6][7][8]26,27 Recent meta-analyses have found a U-shaped association between TSH and the risk of CAD or major adverse cardiovascular events. 8,27 Langen et al 28 found that TSH showed a U-shaped association with total mortality.…”

“…[5][6][7][8]26,27 Recent meta-analyses have found a U-shaped association between TSH and the risk of CAD or major adverse cardiovascular events. 8,27 Langen et al 28 found that TSH showed a U-shaped association with total mortality. In addition, other thyroid hormone like FT3 within the normal range has been found to have a U-shaped association with cardiac function.…”

“…In addition, thyroid homeostasis has been found to be associated with cardiovascular disease. 27 Thyroid homeostasis parameters differed between diabetic and non-diabetic patients and had different relationships with GS or MI (Figure 2), suggesting that different thyroid homeostasis might contribute to the different relationship between hs-TSH and the presence of MI or higher GS in patients with and without diabetes mellitus. Further studies are needed to support our hypothesis.…”

“…It has been reported that thyroid dysfunction including overt or subclinical hyperthyroidism and overt or subclinical hypothyroidism are associated with increased risk of CAD events or CAD mortality. 5–8,26,27 Recent meta-analyses have found a U-shaped association between TSH and the risk of CAD or major adverse cardiovascular events. 8,27 Langen et al 28 found that TSH showed a U-shaped association with total mortality.…”