Pang Gongli, Wang Xiaoxia, Zhao Ru, Yang Peng, Chen Jie, Guo Yanqing, Liang Chendi
Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, Shanxi, China.
Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Int J Cardiol Heart Vasc. 2025 Jul 10;60:101747. doi: 10.1016/j.ijcha.2025.101747. eCollection 2025 Oct.
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.
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.
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.
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.
甲状腺功能障碍可引发多种心血管疾病。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联尚不清楚。本研究的目的是使用双向双样本孟德尔随机化（MR）分析来研究甲状腺功能障碍与PAH之间的因果关联。
分别将甲状腺功能障碍（游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、甲状腺功能亢进和甲状腺功能减退）和PAH用作暴露因素和结局因素。采用逆方差加权（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之间的双向因果关联。使用Cochran's Q检验分析单核苷酸多态性（SNP）之间的异质性。MR-Egger回归和MR-PRESSO的截距项用于分析水平多效性。采用逐一剔除法分析单个SNP对MR分析结果的影响。
IVW显示甲状腺功能减退会增加PAH的风险（OR = 1.485，95%CI [1.051, 2.100]，P = 0.025），而FT3、FT4、TSH和甲状腺功能亢进与PAH风险无关。此外，我们没有发现PAH与甲状腺功能障碍之间存在反向因果关联的证据。
我们的研究发现甲状腺功能减退与PAH风险增加存在因果关联。然而，仍需要进一步研究来说明甲状腺功能障碍与PAH之间的联系。
