High Free T4 Levels Within Reference Range Associated With Atrial Fibrillation

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Higher levels of free T4 that remain within the reference range are associated with a greater prevalence and incidence of atrial fibrillation.

Higher levels of free T4 (fT4) that remain within the reference range are associated with a greater prevalence and incidence of atrial fibrillation, according to findings presented at the Scientific Sessions of the American Heart Association, held November 10-12, 2018, in Chicago, Illinois.

Hyperthyroidism is a known precipitating factor for atrial fibrillation, and findings from the prospective Rotterdam Study, as well as a subsequent meta-analysis, found that patients with elevated fT4 levels within reference range have a higher risk for prevalent and incident atrial fibrillation. In the current study, researchers attempted to validate the association between higher fT4 levels and atrial fibrillation using a large electronic medical record database warehouse. 

The cohort included all patients with a recorded fT4 level in the electronic medical record database warehouse who were not receiving thyroid replacement therapy at initiation of the study (N = 174,914). Researchers divided the reference range of fT4 into quartiles (Q): Q1, 0.75 to 0.90 ng/dL; Q2, 0.91 to 1.01 ng/dL; Q3, 1.02 to 1.14 ng/dL; Q4, 1.15 to 1.50 ng/dL. The cohort was followed for 6.3 ± 4.4 years.

Of the total cohort, 7.4% of patients were below, 88.4% were within, and 4.2% were above the fT4 reference range. The adjusted odds ratio (OR) for prevalent atrial fibrillation was doubled with elevated fT4 vs Q1 (OR, 1.99; P <.0001), but there was also a gradient in risk recorded within the reference range as fT4 levels increased (Q4 vs Q1: OR, 1.40; P <.0001). The 3-year incident atrial fibrillation for low, Q1 to Q4, and high fT4 was 4.1%, 4.1%, 4.3%, 4.5%, 5.2%, and 4.9%, respectively (P <.0001), and prevalent atrial fibrillation was 9.9%, 8.7%, 9.3%, 10.5%, 12.6%, and 14.4%, respectively (P <.0001).

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“These findings validate those of the Rotterdam Study and in a much larger dataset, add to a subsequent meta-analysis, and may have important clinical implications, including a redefinition of the reference range and the target fT4 levels for thyroxine replacement therapy,” the researchers concluded.


Anderson JL, Jacobs V, May HT, et al. Free thyroxine (fT4) within the reference (‘normal’) range predicts risk of atrial fibrillation. Presented at: AHA 2018; November 10-12, 2018; Chicago, Illinois.

This article originally appeared on Endocrinology Advisor