Methods:

The investigators conducted a retrospective cohort study using data on 705,307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004–December 31, 2017, with a median follow-up of 4 years (interquartile range [IQR], 2-9 years). Two cohorts were studied: 701,929 adults aged ≥18 years who initiated thyroid hormone treatment with ≥2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373,981 patients with ≥2 free thyroxine (FT₄) measurements. Data were merged with the National Death Index for mortality ascertainment and cause of death, and analysis was conducted from March 25–September 2, 2020. Time-varying serum thyrotropin and time-varying serum thyrotropin and FT₄ levels (euthyroidism: thyrotropin level, 0.5-5.5 mIU/L; FT₄ level, 0.7-1.9 ng/dL; exogenous hyperthyroidism: thyrotropin level, <0.5 mIU/L; FT₄ level, >1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT₄ level, <0.7 ng/dL) were collected and analyzed. The main outcomes and measure were cardiovascular mortality (i.e., death from cardiovascular causes, including myocardial infarction, heart failure, or stroke). Survival analyses were performed using Cox proportional hazards regression models using serum thyrotropin and FT₄ levels as time-varying covariates.