Revisiting the Thyroid-Heart Axis: Unravelling the Interplay of Hormones, Epigenomes and Precision Cardioprotection.

Thyroid dysfunction (TD) and cardiovascular disease (CVD) commonly coexist in older adults, where age-related vascular, mitochondrial, and autonomic changes heighten sensitivity to even mild hormonal imbalance. Thyroid hormones (THs) regulate cardiac and vascular function through genomic and non-genomic pathways, but aging alters receptor sensitivity, deiodinase (DIO) activity, and epigenetic control, resulting in tissue-specific TH insufficiency despite normal serum levels. Subclinical hypothyroidism (SCH) and low-T3 syndrome are especially prevalent in older adults and are linked to higher risks of heart failure (HF), atherosclerosis, atrial fibrillation, and mortality. Emerging data underscore the role of epigenetic regulators and the gut-thyroid-heart axis in modulating CV responses to TH imbalance. Clinically, routine thyroid function assessment is crucial in CVD, with management tailored to age-related risks. Tissue-selective TH based therapies represent a promising frontier for precision cardioprotection.