Thyroid Function Impact on Cardiac Structure, Function and Disease Risk: Evidence of Causal Associations in European Ancestry

Weiqiang Ruan; Xiaoqin Zhou; Jing Li; Ting Wang; Huizhen Liu; Guiying Zhang; Ke Lin

doi:10.1016/j.hrthm.2024.05.021

Thyroid Function Impact on Cardiac Structure, Function and Disease Risk: Evidence of Causal Associations in European Ancestry

Heart Rhythm. 2024 May 13:S1547-5271(24)02563-3. doi: 10.1016/j.hrthm.2024.05.021. Online ahead of print.

Authors

Weiqiang Ruan¹, Xiaoqin Zhou², Jing Li³, Ting Wang⁴, Huizhen Liu⁴, Guiying Zhang³, Ke Lin⁵

Affiliations

¹ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
² Research Center of Clinical Epidemiology and Evidence-Based Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R. China; Center of Biostatistics, Design, Measurement and Evaluation (CBDME), Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
³ Research Center of Clinical Epidemiology and Evidence-Based Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
⁴ Center of Biostatistics, Design, Measurement and Evaluation (CBDME), Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu 610041, P.R. China.
⁵ Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, P.R. China. Electronic address: pangzai356249@126.com.

PMID: 38750912
DOI: 10.1016/j.hrthm.2024.05.021

Abstract

Background: Thyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality.

Objective: 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 impact on cardiac structure and function assessed by cardiac magnetic resonance imaging.

Methods: A comprehensive two-sample Mendelian randomization (MR) analysis was conducted, utilizing summary data from large-scale meta-analyses of European ancestry individuals.

Results: Genetically determined lower TSH levels (OR 0.928, 95% CI: 0.884 to 0.974, P = 0.003) and genetic risk of hyperthyroidism (OR 1.049, 95% CI: 1.016 to 1.083, P = 0.003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable MR 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.

Conclusions: Our 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.

Keywords: Atrial Fibrillation; Cardiac MRI; Cardiovascular disease; Mendelian randomization; Thyroid function.