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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 had an increased risk of atrial fibrillation (99).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [99]
Citations
Cites
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Impact of Atrial Fibrillation on the Risk of Death: The Framingham Heart Study
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Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study
Heeringa, J., van der Kuip, D. A. M., Hofman, A., Kors, J. A., van Herpen, G., Stricker, B. H. C., Stijnen, T., Lip, G. Y. H., & Witteman, J. C. M. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi825 · Cited by 1,939
Self-citationBianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853
The Rotterdam Study: objectives and design update
Albert Hofman, D., Breteler, M. M. B., van Duijn, C. M., Krestin, G. P., Pols, H. A. P., Stricker, B. H. C., Tiemeier, H. W., Uitterlinden, A. G., Vingerling, J. R., & Witteman, J. C. M. (2007) · European Journal of Epidemiology · doi:10.1007/s10654-007-9199-x · Cited by 1,408
Self-citationLow Serum Thyrotropin Concentrations as a Risk Factor for Atrial Fibrillation in Older Persons
Sawin, C. T., Geller, A., Wolf, P. A., Belanger, A. J., Baker, E., Bacharach, P., Wilson, P., Benjamin, E. J., & D'Agostino, R. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411103311901 · Cited by 1,259
Thyroid Status, Cardiovascular Risk, and Mortality in Older Adults
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The Rotterdam Study: objectives and design update
Albert Hofman, D., Breteler, M. M. B., van Duijn, C. M., Krestin, G. P., Pols, H. A. P., Stricker, B. H. C., Tiemeier, H. W., Uitterlinden, A. G., Vingerling, J. R., & Witteman, J. C. M. (2007) · European Journal of Epidemiology · doi:10.1007/s10654-007-9199-x · Cited by 1,408
Self-citationThyroid hormones and cardiovascular disease
Jabbar, A., Pingitore, A., Pearce, S. H. S., Zaman, A., Iervasi, G., & Razvi, S. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.174 · Cited by 729
The Rotterdam Study: 2018 update on objectives, design and main results
Ikram, M. A., Brusselle, G., Murad, S. D., van Duijn, C. M., Franco, O. H., Goedegebure, A., Klaver, C. C. W., Nijsten, T. E. C., Peeters, R. P., Stricker, B. H. C., et al. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0321-4 · Cited by 447
Self-citationThe Rotterdam Study: 2016 objectives and design update
Albert Hofman, D., Brusselle, G., Murad, S. D., van Duijn, C. M., Franco, O. H., Goedegebure, A., Ikram, M. A., Klaver, C. C. W., Nijsten, T. E. C., Peeters, R. P., et al. (2015) · European Journal of Epidemiology · doi:10.1007/s10654-015-0082-x · Cited by 385
Self-citationThe Rotterdam Study: 2014 objectives and design update
Albert Hofman, D., Murad, S. D., van Duijn, C. M., Franco, O. H., Goedegebure, A., Ikram, M. A., Klaver, C. C. W., Nijsten, T. E. C., Peeters, R. P., Stricker, B. H. C., et al. (2013) · European Journal of Epidemiology · doi:10.1007/s10654-013-9866-z · Cited by 335
Self-citation
Metadata
- 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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