Association of Thyroid Function with Blood Pressure and Cardiovascular Disease: A Mendelian Randomization

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Genetics

Background:

• Thyroid function significantly influences the cardiometabolic system.
• The causal links between subclinical thyroid dysfunction and blood pressure (BP) or cardiovascular diseases (CVD) remain unclear.

Purpose of the Study:

• To investigate the causal association between thyroid function (thyroid-stimulating hormone [TSH], free tetraiodothyronine [FT4], hyper-/hypothyroidism, anti-thyroid peroxidase antibodies [TPOAb]) and BP/CVD.
• Utilizing a two-sample Mendelian randomization (MR) approach.

Main Methods:

• Selected single nucleotide polymorphisms (SNPs) associated with thyroid function markers as instrumental variables from genome-wide association studies (GWAS).
• Assessed SNP-outcome associations for BP and CVD in the Malmö Diet and Cancer Study cohort (n = 29,298).
• Employed inverse-variance weighted (IVW), weighted median, and MR-Egger methods for causal estimate computation.

Main Results:

• Genetically elevated TSH levels were associated with decreased systolic BP and reduced risk of atrial fibrillation.
• Hyperthyroidism and TPOAb showed associations with a lower risk of atrial fibrillation.
• Genetically decreased TSH levels support a causal link with both atrial fibrillation and systolic BP, though caution is advised due to sensitivity analyses.

Conclusions:

• Findings suggest a potential causal role for TSH levels in systolic BP and atrial fibrillation risk.
• The study provides mechanistic insights into the etiology of cardiovascular diseases.
• Further research into thyroid gene functions and cardiovascular outcomes may reveal novel therapeutic pathways.