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Thyroid Hormone Therapy and Incident Stroke.

CONTEXT
Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors.


OBJECTIVE
Determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke.


DESIGN
Retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months.


SETTING
Population-based.


PARTICIPANTS
733,208 thyroid hormone users aged ≥18 years with at least two thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event or study conclusion (406,030 thyroid hormone users with at least two free T4 measurements).


MAIN OUTCOME MEASURES
Incident atrial fibrillation and stroke.


RESULTS
Overall, 71,333/643,687 (11.08%) participants developed incident atrial fibrillation and 41,931/663,809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex and prior history of atrial fibrillation, low TSH or high free T4 levels (i.e., exogenous hyperthyroidism; e.g., TSH<0.1 mIU/L, OR 1.33, 95% CI 1.24-1.43) and high TSH or low free T4 levels (i.e., exogenous hypothyroidism; e.g., TSH>5.5 mIU/L, OR 1.29, 95% CI 1.26-1.33; free T4<0.7 ng/dL, OR 1.29, 95% CI 1.22-1.35) were associated with higher incidence of stroke compared to euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism.


CONCLUSIONS
Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.