Association Between Serum Free Thyroxine Concentration and Atrial Fibrillation
Abstract
BACKGROUND: Previous studies have suggested that minor changes in thyroid function are associated with risk of atrial fibrillation (AF). Our objective was to determine the relationship between thyroid function and presence of atrial fibrillation (AF) in older subjects. METHODS: A population-based study of 5860 subjects 65 years and older, which excluded those being treated for thyroid dysfunction and those with previous hyperthyroidism. Main outcome measures included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin [TSH]) and the presence of AF on resting electrocardiogram. RESULTS: Fourteen subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%), subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23; P<.001). After adjusting for sex, logistic regression showed a higher prevalence of AF in those with subclinical hyperthyroidism compared with euthyroid subjects (9.5% vs 4.7%; adjusted odds ratio, 2.27; P=.01). Median serum free T(4) concentration was higher in those with AF than in those without (1.14 ng/dL; interquartile range [IQR], 1.05-1.27 ng/dL [14.7 pmol/L; IQR, 13.5-16.4 pmol/L] vs 1.10 ng/dL; IQR, 1.00-1.22 ng/dL [14.2 pmol/L; IQR, 12.9-15.7 pmol/L]; P<.001), and higher in those with AF when analysis was limited to euthyroid subjects (1.13 ng/dL; IQR, 1.05-1.26 ng/dL [14.6 pmol/L; IQR, 13.5-16.2 pmol/L] vs 1.10 ng/dL; IQR, 1.01-1.21 ng/dL [14.2 pmol/L; IQR, 13.0-15.6 pmol/L]; P=.001). Logistic regression showed serum free T(4) concentration, increasing category of age, and male sex all to be independently associated with AF. Similar independent associations were observed when analysis was confined to euthyroid subjects with normal TSH values. CONCLUSIONS: The biochemical finding of subclinical hyperthyroidism is associated with AF on resting electrocardiogram. Even in euthyroid subjects with normal serum TSH levels, serum free T(4) concentration is independently associated with AF.
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Atrial arrhythmia has been reported to occur more frequently in euthyroid persons with serum FT4 levels at the upper limit of the reference.
“Atrial arrhythmia has been reported to occur more frequently in euthyroid persons with serum FT 4 levels at the upper limit of the reference [73] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [73]
Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT4 levels and in patients with underlying heart disease.
“Cardiovascular morbidity and mortality are particularly increased in men, in elderly patients with high-normal FT 4 levels and in patients with underlying heart disease [71-73, 76, 77, 87, 91, 92, 94] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [73]
Serum fT4 concentration is independently associated with atrial fibrillation in euthyroid subjects aged 65 years and older.
“the serum fT4 concentration was independently associated with atrial fibrillation in euthyroid subjects 65 years and older (95)”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [95]
Older patients with low TSH and higher fT4 have a higher prevalence and incidence of atrial fibrillation compared with euthyroid subjects.
“Older patients with low TSH and higher fT4 have a higher prevalence and incidence of atrial fibrillation compared with euthyroid subjects (94–98)”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [95]
Subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH.
“Sawin et al. (399) first reported a 2.8-fold increased risk of atrial fibrillation in SH subjects over age 60 years in 1994, and subsequent studies have confirmed that the risk of arrhythmias, particularly atrial fibrillation, is increased in SH (381,384,388,391,400,401).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [400]
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- Authors
- Gammage, M. D.
- Affiliations
- University of Birmingham (GB)
- Corresponding author
- Gammage, M. D.
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2007-05-14
- Volume
- 167
- Issue
- 9
- Pages
- 928
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W1971664482
- Cited by
- 225
- References
- 42
- Citations by year
- 2025: 3 · 2024: 10 · 2023: 5 · 2022: 11 · 2021: 11 · 2020: 10 · 2019: 12 · 2018: 14 · 2017: 13 · 2016: 14 · 2015: 14 · 2014: 11 · 2013: 18 · 2012: 23
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- atrial fibrillation, serum free thyroxine, thyroid function, subclinical hyperthyroidism, subclinical hypothyroidism, overt hypothyroidism, overt hyperthyroidism, older adults, thyroid-stimulating hormone, thyroid hormones, atrial fibrillation risk factors, sex differences, euthyroid subjects, electrocardiogram
- MeSH terms
- Aged, Aged, 80 and over, Atrial Fibrillation, Electrocardiography, Female, Humans, Male, Risk Factors, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine, Cohort Studies, Prevalence, Odds Ratio
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