The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study
Open accessAbstract
OBJECTIVES: To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients. DESIGN: Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level. SETTING: Primary care patients in the city of Copenhagen. SUBJECTS: Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation. MAIN OUTCOME MEASURE: Poisson regression models used to estimate risk of atrial fibrillation by thyroid function. RESULTS: Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation. CONCLUSION: The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.
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A TSH level-dependent association with the risk of atrial fibrillation was found across the whole spectrum of thyroid function in a large population-based cohort study.
“Recently, a TSH level-dependent association with the risk of AF was found across the whole spectrum of thyroid function in a large population-based cohort study [74] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [74]
Compared to euthyroid individuals (TSH 0.4-5 mIU/l), the risk of atrial fibrillation increased with decreasing levels of serum TSH from high-normal thyroid function (TSH 0.2-0.4 mIU/l; adjusted incidence rate ratio 1.12) to mild subclinical hyperthyroidism (TSH 0.1-0.2 mIU/l; IRR 1.16) and grade 2 subclinical hyperthyroidism (TSH <0.1 mIU/l; IRR 1.41).
“Compared to euthyroid individuals (TSH: 0.4-5 mIU/l), the risk of AF increased with decreasing levels of serum TSH from high-normal thyroid function [TSH: 0.2-0.4mIU/l; adjusted incidence rate ratio (IRR) = 1.12] to mild SHyper (TSH: 0.1-0.2mIU/l; IRR = 1.16) and grade 2 SHyper (TSH: <0.1 mIU/l; IRR = 1.41) [74] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [74]
Similar trends were seen for men.
“Similar trends were seen for men.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [401]
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 [401]
Absolute incidence rates of atrial fibrillation were much lower in younger subjects; women under 65 years had incidence rates of 2.3 events per 1000 person-years (relative risk 1.89), while women 65 years and older had incidence rates of 22.7 per 1000 person-years (relative risk 1.27).
“However, absolute incidence rates of atrial fibrillation were much lower in younger subjects; for example, women under the age of 65 years had atrial fibrillation incidence rates of 2.3 events per 1000 personyears (relative risk of 1.89 compared to age-matched euthyroid women), while women 65 years and older had incidence rates of 22.7 per 1000 person-years (relative risk of 1.27 compared to age-”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [401]
In the largest study to date (586,460 people followed for a median of 5.5 years), the highest relative risk for atrial fibrillation occurred in younger subjects and in subjects with lower TSH levels.
“In the largest study to date (586,460 people followed for a median of 5.5 years), the highest relative risk for atrial fibrillation occurred in younger subjects, possibly because other causes predominate with age, and in subjects with lower TSH levels (401).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [401]
Subclinical hyperthyroidism is associated with increased atrial fibrillation in all subjects.
“Some of these studies re-ported increased risks of overall mortality in older subjects (380,429), cardiovascular events (391), heart failure (381), and atrial fibrillation in all subjects (401) or in older subjects (384), and vertebral fractures in older women (408).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [401]
Thyroid dysfunction is independently associated with AF, with hypothyroidism HR 1.23, subclinical hyperthyroidism RR 1.31, and overt hyperthyroidism RR 1.42 compared with euthyroid.
“Thyroid dysfunction 206, 207 hypothyroidism subclinical hyperthyroidism overt hyperthyroidism (reference: euthyroid) HR 1.23 (95% CI 0.77-1.97)RR 1.31 (95% CI 1.19-1.44)RR 1.42 (95% CI 1.22-1.63)”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [206]
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Background2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- 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., & Gislason, G. H.
- Affiliations
- Gentofte Hospital (DK)
- University of Copenhagen (DK)
- Roskilde Sygehus (DK)
- Corresponding author
- Selmer, C.
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2012-11-27
- Volume
- 345
- Issue
- nov27 1
- Pages
- e7895-e7895
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC3508199
- OpenAlex
- W2015178517
- Cited by
- 323
- References
- 43
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 22 · 2023: 43 · 2022: 21 · 2021: 21 · 2020: 33 · 2019: 25 · 2018: 28 · 2017: 21 · 2016: 21 · 2015: 20 · 2014: 23 · 2013: 14 · 2012: 1
- FWCI
- 14.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Hjerteforeningen
- 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, thyroid dysfunction, thyroid-stimulating hormone, subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, overt hypothyroidism, thyroid function, cardiovascular risk
- MeSH terms
- Atrial Fibrillation, Denmark, Female, Follow-Up Studies, Humans, Male, Middle Aged, Population Surveillance, Registries, Retrospective Studies, Risk Factors, Thyroid Diseases, Incidence
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