Causal Relationship Between Hypothyroidism and Multiple Cardiovascular Diseases: A Bidirectional Mendelian Randomization Study

Objective: Hypothyroidism is associated with a variety of cardiovascular diseases, but whether they are causally related to each other is unclear. This study intends to explore the bidirectional causal relationship between hypothyroidism and four common cardiovascular diseases using Mendelian randomization (MR). Methods: Single‐nucleotide polymorphisms (SNPs), the instrumental variable required for the study, were obtained from the public genome‐wide association study (GWAS) database, and samples were obtained from European populations. Causal effects were assessed using three methods: inverse variance weighted (IVW), MR‐Egger regression, and weighted median (WM), with IVW being the main method. Sensitivity analyses were conducted using MR‐PRESSO, Cochran’s Q test, MR‐Egger regression intercept term, and leave‐one‐out method to assess the reliability and stability of the study results. Results: The results of IVW method showed a causal effect of hypothyroidism on coronary heart disease (CHD) (OR: 2.313, 95% CI: 1.271 to 4.208, p = 0.006) and hypertension (OR: 2.293, 95% CI: 1.331 to 3.955, p = 0.003). In contrast, there was no causal effect of hypothyroidism on arrhythmias (OR: 1.448, 95% CI: 0.885 to 2.371, p = 0.141) and heart failure (OR: 1.512, 95% CI: 0.775 to 2.951, p = 0.226). The results of MR‐PRESSO and Cochran’s Q test showed that there was no heterogeneity in the instrumental variables included to study the effect of hypothyroidism on CHD, while there was heterogeneity in the instrumental variables included to study the effect on hypertension; also, the results of the MR‐Egger regression intercept term showed that none of the included instrumental variables were horizontally pleiotropic. The results of the reverse MR analysis showed no causal effect of any of the four cardiovascular diseases on hypothyroidism. Conclusion: Patients with hypothyroidism are more likely to develop CHD as well as hypertension.