AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Free Thyroxine Levels and Risk of Incident Atrial Fibrillation Among Levothyroxine Treated Adults with Hypothyroidism
By Karthikeyan S, sheikh M, Linz M et al.
Background: Levothyroxine is the standard treatment for hypothyroidism, with thyroid-stimulating hormone (TSH) serving as the primary therapeutic target. However, whether variation in free thyroxine (fT4) levels among treated patients independently influences atrial fibrillation (AF) risk remains unclear. We evaluated the association between fT4 levels and incident AF among levothyroxine-treated adults with hypothyroidism. Methods: Using the All of Us Research Program, we identified adults with hypothyroidism receiving levothyroxine who had available fT4 measurements and no prior diagnosis of AF. Median fT4 and TSH values were calculated for each participant to reflect longitudinal thyroid hormone exposure, and fT4 was categorized into quartiles. Participants were followed from their first available fT4 measurement until incident AF or end of observation. Cox proportional hazards models evaluated the association between increasing fT4 quartile and incident AF after adjustment for TSH, age, sex, hypertension, diabetes mellitus, coronary artery disease, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, and obstructive sleep apnea. Results: Among 16,251 levothyroxine-treated adults (mean age 53.5 ± 14.1 years; 78.3% female), 1,311 developed incident AF during follow-up. Increasing fT4 quartile was associated with higher AF risk in unadjusted analysis (HR 1.06, 95% CI 1.01-1.11; p=0.022). The association remained significant after adjustment for TSH and cardiometabolic comorbidities (HR 1.11, 95% CI 1.05-1.16; p<0.001) and in the fully adjusted model including age and sex (HR 1.09, 95% CI 1.04-1.14; p<0.001). Older age was associated with increased AF risk (HR 1.04 per year, 95% CI 1.04-1.05; p<0.001), while female sex was associated with lower AF risk (HR 0.70, 95% CI 0.62-0.79; p<0.001). Conclusions: Higher fT4 levels were independently associated with an increased hazard of incident AF among levothyroxine-treated adults with hypothyroidism, even after adjustment for age, sex, TSH, and major cardiometabolic comorbidities. The persistence of this association following TSH adjustment suggests that differences in fT4 levels among treated patients may influence AF risk beyond traditional markers of thyroid status. These findings support careful monitoring of thyroid hormone replacement and warrant further investigation into optimal treatment targets for AF risk reduction.