Genetically predicted hypothyroidism, thyroid hormone treatment, and the risk of cardiovascular diseases: a mendelian randomization study.

Genetically predicted hypothyroidism was significantly associated with increased risk of myocardial infarction.

• Odds ratio for hypothyroidism and myocardial infarction: OR 15.11, 95% CI: 2.93–77.88
• Two-sample Mendelian randomization analysis was performed using inverse-variance weighting as the primary method
• Genetic instrumental variables were obtained from large publicly available genome-wide association studies
• Results remained stable after adjusting for confounding factors including SBP, DBP, BMI, diabetes, cholesterol, LDL, triglycerides, and metformin

Genetically predicted levothyroxine treatment was significantly associated with increased risk of myocardial infarction.

• Odds ratio for levothyroxine treatment and myocardial infarction: OR 3.75, 95% CI: 1.80–7.80
• Levothyroxine treatment refers to participants taking the medication levothyroxine sodium
• Results remained stable in multivariable Mendelian randomization after adjusting for confounding factors
• MR-Egger regression, Cochran's Q statistic, and leave-one-out analysis were used to ensure reliability

Levothyroxine treatment was significantly associated with increased risk of heart failure.

• Odds ratio for levothyroxine treatment and heart failure: OR 2.16, 95% CI: 1.21–3.88
• No significant association was detected between hypothyroidism and heart failure risk
• Results remained stable after adjusting for confounding factors in multivariable Mendelian randomization

No significant associations were detected between hypothyroidism or levothyroxine treatment and the risk of cardiac death.

• Neither hypothyroidism nor levothyroxine treatment showed significant associations with cardiac death
• Cardiac death was one of three cardiovascular outcomes examined alongside myocardial infarction and heart failure
• Findings were consistent across primary and sensitivity analyses

Atrial fibrillation and stroke were identified as potential mediators in the relationship between levothyroxine treatment and cardiovascular risk.

• Mediation analysis was conducted treating atrial fibrillation and stroke as mediator variables for the levothyroxine treatment associations
• Atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction
• Bradycardia was examined as a mediator variable for the hypothyroidism associations
• Mediation analysis was employed in addition to the primary two-sample Mendelian randomization framework

Multivariable Mendelian randomization adjusting for multiple confounding factors confirmed the stability of the primary findings.

• Confounding factors adjusted for included systolic blood pressure, diastolic blood pressure, BMI, diabetes, cholesterol, LDL, triglycerides, and metformin
• After adjusting for these confounding factors, the results remained stable
• Sensitivity analyses included MR-Egger regression, Cochran's Q statistic, and leave-one-out analysis