Abstract

Background: Subclinical hypothyroidism, characterised by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (fT4) levels, is common among individuals aged over 50 years and is associated with adverse health outcomes. However, the impact of levothyroxine (LT4) treatment on cardiovascular and bone health in this population remains uncertain.
Methods: We conducted a retrospective cohort study and an emulated target trial using healthcare records from The Health Improvement Network (THIN), a database of anonymised primary care records covering 6% of the United Kingdom population, which is broadly representative of the general population. The cohort study included 53,899 individuals for cardiovascular outcomes and 56,878 individuals for bone health outcomes. The emulated target trial included 17,755 participants for cardiovascular outcomes and 19,364 participants for bone health outcomes.
Results: In the cohort study with a 10-year follow-up, the adjusted time-varying hazard ratio was 0.91 (95% CI: 0.87-0.97, p < 0.001) for cardiovascular events and 1.21 (95% CI: 1.14-1.28, p < 0.001) for bone health outcomes. In the emulated target trial with a 10-year follow-up, the adjusted time-varying hazard ratio for cardiovascular events was 0.78 (95% CI: 0.71-0.86, p < 0.001), and for bone health outcomes, it was 1.26 (95% CI: 1.15-1.39, p < 0.001).
Conclusion: Our findings highlight consistent results between the cohort study and emulated target trial, indicating potential protective cardiovascular effects and adverse bone health outcomes associated with LT4 treatment in individuals with subclinical hypothyroidism aged over 50 years. Combining bone protection alongside LT4 treatment may be beneficial in these patients.