Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study.
BACKGROUND
Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking.


OBJECTIVE
This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns.


METHODS
From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997-2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases.


METHODS
Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF.


RESULTS
Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19-2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants ≤ 65 y from 1-9% and from 6-12% in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c-statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF.


CONCLUSIONS
There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction.
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Layal
L
Chaker
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Jan
J
Heeringa
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Abbas
A
Dehghan
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Marco
M
Medici
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
W Edward
WE
Visser
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Christine
C
Baumgartner
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Albert
A
Hofman
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Nicolas
N
Rodondi
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Robin P
RP
Peeters
Rotterdam Thyroid Center (L.C., M.M., W.E.V., R.P.P.), Department of Internal Medicine (L.C., M.M., W.E.V., R.P.P.), and Department of Epidemiology (L.C., J.H., A.D., A.H., O.H.F.), Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of General Internal Medicine (C.B., N.R.), Inselspital, University Hospital of Bern, 3010 Bern, Switzerland.
Oscar H
OH
Franco
D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012306:Risk; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D013972:Thyrotropin; D013974:Thyroxine