Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans

Importance: Cardiovascular disease is the leading cause of death in the United States. Synthetic thyroid hormones are among the 3 most commonly prescribed medications, yet studies evaluating the association between the intensity of thyroid hormone treatment and cardiovascular mortality are scarce. Objective: To evaluate the association between thyroid hormone treatment intensity and cardiovascular mortality. Design, Setting, and Participants: This retrospective cohort study used data on 705 307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004, and December 31, 2017, with a median follow-up of 4 years (IQR, 2-9 years). Two cohorts were studied: 701 929 adults aged 18 years or older who initiated thyroid hormone treatment with at least 2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373 981 patients with at least 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 to September 2, 2020. Exposures: 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, 1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT4 level, 1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (eg, 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. Conclusions and Relevance: This study suggests that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.