Thyroid Hormone Therapy and Incident Stroke

Abstract

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

Objective: We aimed to determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke.

Methods: We conducted a retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. The study population comprised 733 208 thyroid hormone users aged ≥18 years with at least 2 thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event (atrial fibrillation or stroke) or study conclusion (406 030 thyroid hormone users with at least 2 free thyroxine [T4] measurements).

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, higher incidence of stroke was associated with low TSH or high free T4 levels (ie, exogenous hyperthyroidism; eg, TSH <0.1 mIU/L; OR 1.33; 95% CI, 1.24-1.43; free T4>1.9 ng/dL, OR 1.17, 95% CI 1.06-1.30) and high TSH or low free T4 levels (ie, exogenous hypothyroidism; eg, 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) compared with 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.

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

Keywords: atrial fibrillation; stroke; thyroid hormone therapy.

Figure 1.

Study flow diagram.

Figure 2.

A, Cumulative risk of incident atrial fibrillation by TSH category. Patients with a TSH <0.1 mIU/L and TSH >5.5 mIU/L, but not those with a TSH 0.1-0.5 mIU/L, had an increased risk of incident atrial fibrillation over time compared with euthyroid individuals (TSH >0.5-5.5 mIU/L). B, Cumulative risk of incident atrial fibrillation by free T4 category. Patients with a free T4 >1.9 ng/dL had an increased risk of incident atrial fibrillation over time compared with euthyroid individuals (free T4 0.7-1.9 ng/dL). C, Cumulative risk of incident stroke by TSH category. Patients with a TSH <0.1 mIU/L and TSH >5.5 mIU/L, but not those with a TSH 0.1-0.5 mIU/L, had an increased risk of incident stroke over time compared with euthyroid individuals (TSH >0.5-5.5 mIU/L). D. Cumulative risk of incident stroke by free T4 category. Patients with a free T4 <0.7 ng/dL had an increased risk of incident stroke over time compared with euthyroid individuals (free T4 0.7-1.9 ng/dL).