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The Rotterdam Study

Jan Heeringa, MD; E. H. Hoogendoorn, MD; W. M. van der Deure, MD; Albert Hofman, MD, PhD; R. P. Peeters, MD, PhD; W. C. J. Hop, PhD; M. den Heijer, MD, PhD; Theo J. Visser, PhD; Jacqueline C. M. Witteman, PhD

Arch Intern Med. 2008;168(20):2219-2224.

Background  Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fibrillation. We aimed to investigate the association of high-normal thyroid function with the development of atrial fibrillation in a prospective population-based study in the elderly.

Methods  The association between thyroid-stimulating hormone (TSH) levels and atrial fibrillation was examined in 1426 subjects with TSH levels in the normal range (0.4-4.0 mU/L) and without atrial fibrillation at baseline. In 1177 of the 1426 persons in this group, we also examined the association between free thyroxine levels within the normal range (0.86-1.94 ng/dL [to convert to picomoles per liter, multiply by 12.871]) and atrial fibrillation. During a median follow-up of 8 years, 105 new cases of atrial fibrillation were identified. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs) using Cox proportional hazards models after adjustment for age, sex, current smoking, former smoking, body mass index, systolic blood pressure, hypertension, history of myocardial infarction, presence of heart failure, left ventricular hypertrophy on the electrocardiogram, diabetes mellitus, total cholesterol level, and time of the drawing of blood samples.

Results  The risk of atrial fibrillation was associated with the TSH level. The multivariate adjusted HR was 1.94 (95% CI, 1.13-3.34, lowest vs highest quartile; P for trend, .02). The multivariate adjusted level of free thyroxine showed a graded association with risk of atrial fibrillation (HR, 1.62; 95% CI, 0.84-3.14, highest vs lowest quartile; P for trend, .06).

Conclusion  Within the normal range of thyroid parameters, persons with high-normal thyroid function are at an increased risk of atrial fibrillation.

Author Affiliations: Departments of Epidemiology and Biostatistics (Drs Heeringa, Hofman, Hop, Visser, and Witteman) and Internal Medicine (Drs van der Deure and Peeters), Erasmus Medical Center, Rotterdam, and Department of Internal Medicine, University Medical Center Nijmegen, Nijmegen (Drs Hoogendoorn and den Heijer), the Netherlands.
Deceased.