Normal Thyroid Function and the Risk of Atrial Fibrillation: the Rotterdam Study

J Clin Endocrinol Metab. 2015 Oct;100(10):3718-24. doi: 10.1210/jc.2015-2480. Epub 2015 Aug 11.


Context: 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.

Design, setting, and participants: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / epidemiology*
  • Atrial Fibrillation / physiopathology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prevalence
  • Risk
  • Thyroid Function Tests
  • Thyroid Gland / physiopathology*
  • Thyrotropin / blood
  • Thyroxine / blood


  • Thyrotropin
  • Thyroxine