High Free T4 Levels Within Reference Range Associated With Atrial Fibrillation

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These findings may have important clinical implications including a redefinition of the reference range and the target fT4 levels for thyroxine replacement therapy.
These findings may have important clinical implications including a redefinition of the reference range and the target fT4 levels for thyroxine replacement therapy.

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).

“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.

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Reference

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.

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