Thyroid dysfunction and pulmonary arterial hypertension: A bidirectional mendelian randomization study

IF 2.5 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

IJC Heart and Vasculature Pub Date : 2025-07-10 DOI:10.1016/j.ijcha.2025.101747

Gongli Pang , Xiaoxia Wang , Ru Zhao , Peng Yang , Jie Chen , Yanqing Guo , Chendi Liang

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引用次数: 0

Abstract

Objective

Thyroid dysfunction can cause several cardiovascular diseases. Studies have suggested a link between thyroid dysfunction and an increased risk of Pulmonary Arterial Hypertension (PAH). However, the causal association between this link is unknown. The aim of this study was to investigate the causal association between thyroid dysfunction and PAH using bidirectional two-sample Mendelian Randomization (MR) analysis.

Method

Thyroid dysfunction (Free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), hyperthyroidism and hypothyroidism) and PAH were respectively used as exposure and outcome factors. The bidirectional causal association between thyroid dysfunction and PAH was analyzed by using Inverse Variance Weighting (IVW), MR-Egger regression (MR-Egger), and Weighted Median (WM) methods. Cochran’s Q test was used to analyze the heterogeneity among single nucleotide polymorphisms (SNPs). The intercept term of MR-Egger regression and MR-PRESSO were used to analyze horizontal pleiotropy. The effect of single SNP on the MR analysis results was analyzed by leave-one-out method.

Results

The IVW showed that hypothyroidism could increase the risk of PAH (OR = 1.485, 95 % CI [1.051, 2.100], P = 0.025), while FT3, FT4, TSH and hyperthyroidism were not associated with the risk of PAH. Furthermore, we found no evidence of reverse causal association between PAH and thyroid dysfunction.

Conclusion

Our study found that hypothyroidism is causally associated with an increased risk of PAH. However, further investigations are still needed to illustrate the connection between thyroid dysfunction and PAH.

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甲状腺功能障碍和肺动脉高压：一项双向孟德尔随机研究

目的甲状腺功能障碍可引起多种心血管疾病。研究表明，甲状腺功能障碍与肺动脉高压（PAH）风险增加之间存在联系。然而，这种联系之间的因果关系尚不清楚。本研究的目的是利用双向双样本孟德尔随机化（MR）分析探讨甲状腺功能障碍与多环芳烃之间的因果关系。方法以甲状腺功能障碍（游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）、甲状腺功能亢进和甲状腺功能减退）和多环芳烃（PAH）分别作为暴露和转归因素。采用反方差加权（IVW）、MR-Egger回归（MR-Egger）和加权中位数（WM）方法分析甲状腺功能障碍与PAH之间的双向因果关系。采用Cochran’s Q检验分析单核苷酸多态性（snp）的异质性。采用MR-Egger回归的截距项和MR-PRESSO分析水平多效性。单SNP对MR分析结果的影响采用留一法分析。结果IVW结果显示，甲状腺功能减退可增加PAH发病风险（OR = 1.485, 95% CI [1.051, 2.100], P = 0.025），而FT3、FT4、TSH、甲亢与PAH发病风险无相关性。此外，我们没有发现多环芳烃与甲状腺功能障碍之间反向因果关系的证据。结论：我们的研究发现甲状腺功能减退与多环芳烃风险增加有因果关系。然而，甲状腺功能障碍与多环芳烃之间的关系仍需进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

IJC Heart and Vasculature Medicine-Cardiology and Cardiovascular Medicine

CiteScore

4.90

自引率

10.30%

发文量

216

审稿时长

56 days

期刊介绍： IJC Heart & Vasculature is an online-only, open-access journal dedicated to publishing original articles and reviews (also Editorials and Letters to the Editor) which report on structural and functional cardiovascular pathology, with an emphasis on imaging and disease pathophysiology. Articles must be authentic, educational, clinically relevant, and original in their content and scientific approach. IJC Heart & Vasculature requires the highest standards of scientific integrity in order to promote reliable, reproducible and verifiable research findings. All authors are advised to consult the Principles of Ethical Publishing in the International Journal of Cardiology before submitting a manuscript. Submission of a manuscript to this journal gives the publisher the right to publish that paper if it is accepted. Manuscripts may be edited to improve clarity and expression.