Thyroid function and atrial fibrillation: Is there a mediating role for epicardial adipose tissue?

Daniel Bos,1–3,* Arjola Bano,2,4,5,* Albert Hofman,1,2 Tyler J VanderWeele,1 Maryam Kavousi,2 Oscar H Franco,2 Meike W Vernooij,2,3 Robin P Peeters,2,4,5 M Arfan Ikram,1,2 Layal Chaker,1,2,4,5 1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; 2Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; 3Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; 4Academic Center for Thyroid Diseases, Erasmus MC, Rotterdam, The Netherlands; 5Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands *These authors contributed equally to this work Background: The underlying mechanism of the association between thyroid function and atrial fibrillation (AF) is poorly understood, but epicardial adipose tissue (EAT) could be a promising mediator.Methods: In the 1995 participants (mean age 64.5 years) from the population-based Rotterdam Study, we measured thyroid function (thyroid-stimulating hormone, free thyroxine [FT4]) and performed computed tomography to quantify EAT volumes. All participants were followed for the occurrence of AF. We assessed associations of thyroid-stimulating hormone and FT4 with EAT and AF and performed causal mediation analysis to decompose the overall effect of thyroid function on AF with EAT as mediator.Results: Higher FT4 levels were associated with larger EAT volumes in persons with large waist circumferences, defined by sex-specific cutoffs (0.08 mL more EAT per 1-SD increase in FT4, 95% CI: 0.02, 0.14), but not in persons with a normal waist circumference. In persons with a large waist circumference, higher FT4 levels were associated with a higher AF risk (hazard ratio 1.50, 95% CI: 1.22, 1.83). We found no evidence of a mediating role of EAT in the association of thyroid function with AF (mediated interaction 1.6%, pure indirect effect 3.2%). The estimate of reference interaction of EAT with thyroid function on AF risk was more substantial (10.8