High-Normal Thyroid Function and Risk of Atrial Fibrillation: The Rotterdam Study
Abstract
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.
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Old individuals with TSH in the lowest quartile and fT4 in the highest quartile of the normal range have an increased risk of atrial fibrillation.
“old individuals with TSH in the lowest quartile and fT4 in the highest quartile of the normal range had an increased risk of atrial fibrillation (99).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [99]
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A large-scale association analysis of 68 thyroid hormone pathway genes with serum TSH and FT4 levels
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“In addition, the serum fT4 concentration was independently associated with atrial fibrillation in euthyroid subjects 65 years and older (95) and old individuals with TSH in the lowest quartile and fT4 in the highest quartile of the normal range had an increased risk of atrial fibrillation (99).”
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- Authors
- Heeringa, J., Hoogendoorn, E. H., van der Deure, W. M., Hofman, A., Peeters, R. P., Hop, W. C. J., den Heijer, M., Visser, T. J., & Witteman, J. C. M.
- Affiliations
- Erasmus MC (NL)
- ORCID
- Peeters, R. P.
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2008-11-10
- Volume
- 168
- Issue
- 20
- Pages
- 2219
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2145070197
- Cited by
- 161
- References
- 39
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 12 · 2018: 7 · 2017: 11 · 2016: 16 · 2015: 11 · 2014: 8 · 2013: 17 · 2012: 12
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- atrial fibrillation, thyroid function, thyroid-stimulating hormone, free thyroxine, subclinical hyperthyroidism, older adults, cardiovascular risk factors, thyroid hormones
- MeSH terms
- Aged, Atrial Fibrillation, Female, Heart Rate, Humans, Hyperthyroidism, Male, Prospective Studies, Thyrotropin, Thyroxine, Proportional Hazards Models
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