Thyroid function effect on cardiac structure, cardiac function, and disease risk: Evidence of causal associations in European ancestry

Abstract

BackgroundThyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality. ObjectiveThe purpose of this study was to investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their effect on cardiac structure and function assessed by cardiac magnetic resonance imaging. MethodsA comprehensive 2-sample Mendelian randomization analysis was performed using summary data from large-scale meta-analyses of European ancestry individuals. ResultsGenetically determined lower TSH levels (odds ratio 0.928; 95% confidence interval 0.884–0.974; P = .003) and genetic risk of hyperthyroidism (odds ratio 1.049; 95% confidence interval 1.016–1.083; P = .003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable Mendelian randomization revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function. ConclusionOur study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias.