Thyroid function, cardiometabolic health and general health in middle aged and older adults

Thyroid hormones have complex pleiotropic effects, that vary depending on the targeted organs and tissues. The resultant of all the specific effects of thyroid hormones is likely reflected in general health. However, the role of thyroid hormones on specific aspects of cardiometabolic health remains controversial. In addition, the role of thyroid hormones on general health is largely unclear.
This thesis focuses on the association of thyroid function with cardiometabolic health and general health. Most of the included studies are embedded within the Rotterdam Study, a large prospective population‐based cohort study in middle‐aged and older adults.
The first aim of the thesis is to extend the current knowledge about the role of thyroid function on cardiometabolic health. Specifically, we investigate the association of thyroid function with local fat, fibrosis, atherosclerosis, and coagulation, respectively. We find that low and lownormal thyroid function are associated with an increased risk of nonalcoholic fatty liver disease and fibrotic diseases. On the other hand, high and high‐normal thyroid function are associated with increasing levels of procoagulant factors, and increased risk of subclinical atherosclerosis and atherosclerotic cardiovascular events. In order to provide some mechanistic evidence, we also investigate the mechanisms that can explain certain cardiovascular effects of thyroid hormones. Our results indicate that fibrinogen and von Willebrand factor can partially mediate the link of thyroid function with cardiovascular disease. Besides, the occurrence of AF may be influenced by synergic effects between thyroid hormones and EAT.
The second aim of the thesis is to yield novel insights about the qualitative and quantitative impact of thyroid function on general health. We thus adopt a broader perspective, using multidimensional measures that can reflect the pleiotropic effects of thyroid hormones, such as frailty index, global gait, and measurements of life expectancy. We find that increasing levels of circulating free thyroxine are associated with an increased risk of health deterioration over time. Furthermore, we observe meaningful differences in total and disease‐specific life expectancy, within the reference ranges of thyroid function. Subjects with low‐normal thyroid function live longer overall, and also live more years with and without non‐communicable diseases than those with high‐normal thyroid function.
Overall, the findings of this thesis suggest that the clinical consequences of thyroid dysfunction are extended even within the reference ranges of thyrotropin and free thyroxine levels, thus providing supporting evidence for a reevaluation of the current reference ranges of thyroid function.