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BACKGROUND

Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown.

METHODS

The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined.

RESULTS

Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82, P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88, P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86, P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98, P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97, P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99, P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82, P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97, P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI.

CONCLUSIONS

Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.


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Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study

Show Author's information Jing-Jia WANG1Zhen-Huang ZHUANG2,3Can-Qing YU2,3Wen-Yao WANG1Wen-Xiu WANG2,3Kuo ZHANG1Xiang-Bin MENG4Jun GAO4Jian TIAN1Ji-Lin ZHENG1Jie YANG1Tao HUANG2,3,5Chun-Li SHAO4( )Yi-Da TANG4( )
Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China
Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, Beijing, China
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China
Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China

Abstract

BACKGROUND

Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown.

METHODS

The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined.

RESULTS

Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04−0.82, P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18−0.88, P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42−0.86, P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49−0.98, P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27−0.97, P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68−0.99, P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32−0.82, P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81−0.97, P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI.

CONCLUSIONS

Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

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Acknowledgements

Publication history

Published: 28 January 2022
Issue date: January 2022

Copyright

© 2022 JGC All rights reserved

Acknowledgements

We sincerely acknowledge the original GWASs and the related consortiums (FinnGen, CARDIoGRAM, CARDIoGRAMplusC4DDIAGRAM, CHARGE, MEGASTROKE) for the collection and management of the large-scale data resources. We also want to acknowledge the participants and investigators of the studies in our research.

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