Free thyroxine within the normal reference range predicts risk of atrial fibrillation
Abstract
Introduction: Hyperthyroidism is a known precipitating factor for atrial fibrillation (AF). However, recent reports have suggested an increased risk of AF with free thyroxine (fT4) levels even within the upper reference (normal) range. We sought to test whether higher fT4 levels within the reference range are associated with an increased risk of AF. Methods and Results: All patients in the Intermountain Healthcare electronic medical record database with an fT4 level not on thyroid medication were included. The reference range of fT4 was divided into quartiles (Q), and associations with prevalent and incident AF were assessed by multivariable regression. Similar analyses were performed for thyroid stimulating hormone (TSH) and total and free T3. A total of 174 914 patients were included and followed for 7.0 ± 4.9 years. Of these, 7.4%, 88.4%, and 4.2% had fT4 levels below, within, and above the reference range. As expected, prevalent AF was greater with elevated fT4. However, gradients also were noted within the reference range, comparing Q4 to Q1, for prevalent AF (adjusted odds ratio 1.4, P < .0001) and incident AF (adjusted hazard ratio 1.16, P < .0001). In contrast, no relationship with AF prevalence and incidence was noted for total and free T3 within their reference ranges, and the pattern for TSH was uninformative. Conclusion: Higher fT4 levels within the reference range were associated with an increased prevalence and incidence of AF. These findings in a large dataset prospectively validate earlier reports and may have important implications, including a redefinition of the normal range and fT4 targets for replacement therapy.
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In that analysis, no relationship was noted for serum total T3 and fT3 within their normal reference ranges with AF.
“but no relationship was noted for serum total T3 and fT3 within their normal reference ranges (62).”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [62]
In an analysis of 174,914 patients followed for 7.0 ± 4.9 years, incidence and prevalence of AF was greater with elevated serum fT4 levels even within the normal reference range.
“The first is an analysis of 174,914 patients followed for 7.0 ± 4.9 years. It revealed that the incidence and prevalence of AF was greater with elevated serum fT4 levels, even within the normal reference range”
From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [62]
Cites
Miyasaka, Y., Barnes, M. E., Gersh, B. J., Cha, S. S., Bailey, K. R., Abhayaratna, W. P., Seward, J. B., & Tsang, T. S. M. (2006) · Circulation · doi:10.1161/circulationaha.105.595140 · Cited by 2,564 · see citing works
Lifetime Risk for Development of Atrial Fibrillation: The Framingham Heart Study
Lloyd-Jones, D. M., Wang, T. J., Leip, E. P., Larson, M. G., Levy, D., Vasan, R. S., D’Agostino, R. B., Massaro, J. M., Beiser, A., Wolf, P. A., et al. (2004) · Circulation · doi:10.1161/01.cir.0000140263.20897.42 · Cited by 2,041 · see citing works
Schnabel, R. B., Yin, X., Gona, P., Larson, M. G., Beiser, A. S., McManus, D. D., Newton-Cheh, C., Lubitz, S. A., Magnani, J. W., Ellinor, P. T., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61774-8 · Cited by 1,746 · see citing works
Global epidemiology of atrial fibrillation
Rahman, F., Kwan, G. F., & Benjamin, E. J. (2014) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2014.118 · Cited by 731 · see citing works
Selmer, C., Olesen, J. B., Hansen, M. L., Lindhardsen, J., Olsen, A.-M. S., Madsen, J. C., Faber, J., Hansen, P. R., Pedersen, O. D., Torp-Pedersen, C., et al. (2012) · BMJ · doi:10.1136/bmj.e7895 · Cited by 323 · see citing works
A Review of the Clinical Consequences of Variation in Thyroid Function Within the Reference Range
Taylor, P. N., Razvi, S., Pearce, S. H., & Dayan, C. M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1315 · Cited by 274 · see citing works
High-Normal Thyroid Function and Risk of Atrial Fibrillation: The Rotterdam Study
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. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.20.2219 · Cited by 161 · see citing works
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Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism
Idrees, T., Palmer, S., Maciel, R. M. B., & Bianco, A. C. (2020) · Thyroid® · doi:10.1089/thy.2020.0153 · Cited by 58 · see citing works
- Authors
- Anderson, J. L., Jacobs, V., May, H. T., Bair, T. L., Benowitz, B. A., Lappe, D. L., Muhlestein, J. B., Knowlton, K. U., & Bunch, T. J.
- Affiliations
- University of Utah (US)
- Intermountain Medical Center (US)
- Corresponding author
- Anderson, Jeffrey L.
- ORCID
- Venue
- Journal of Cardiovascular Electrophysiology
- Publisher
- Wiley
- Published
- 2019-11-17
- Volume
- 31
- Issue
- 1
- Pages
- 18-29
- ISSN
- 1045-3873 (ISSN-L)
- 1540-8167
- OpenAlex
- W2972753888
- Cited by
- 22
- References
- 7
- Citations by year
- 2026: 1 · 2024: 8 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 1
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Electrophysiology (publishedVersion)
- PubMed (publishedVersion)
- 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
- free thyroxine, atrial fibrillation, thyroid function, hyperthyroidism, thyroid-stimulating hormone, free triiodothyronine, atrial fibrillation risk, thyroid hormone replacement
- MeSH terms
- Aged, Atrial Fibrillation, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Reference Values, Retrospective Studies, Risk Factors, Thyroid Diseases, Thyroxine, United States, Biomarkers, Incidence, Prevalence, Databases, Factual, Electronic Health Records
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