Thyroid Hormone Treatment Intensity and Cardiovascular Morta
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.

Of the 705,307 patients in the study, 625,444 (88.7%) were men, and the median age was 67 years (IQR, 57-78 years; range, 18-110 years). Overall, 75,963 patients (10.8%) died of cardiovascular causes. After adjusting for age, sex, traditional cardiovascular risk factors (e.g., hypertension, smoking, and previous cardiovascular disease or arrhythmia), patients with exogenous hyperthyroidism (e.g., thyrotropin levels, <0.1 mIU/L: adjusted hazard ratio [AHR], 1.39; 95% confidence interval [CI], 1.32-1.47; FT4 levels, >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (e.g., thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55-2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50-1.63) had increased risk of cardiovascular mortality compared with individuals with euthyroidism.

The authors concluded that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality.