Does High-Normal Thyroid Function Increase Risk for Atrial Fibrillation?
Selmer C, Olesen JB, Hansen ML, Lindhardsen J, Olsen AM, Madsen JC, Faber J, Hansen PR, Pedersen OD, Torp-Pedersen C, Gislason GH. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. November 27, 2012 [Epub ahead of print].
SUMMARY • • • • • • • • • • • • • • • • • • • • • • • •
Background
Patients with subclinical and overt hyperthyroidism are known to be at increased risk for the development of atrial fibrillation (1–5). However, the risk for incident atrial fibrillation had not previously been assessed in a very large population across the whole spectrum of thyroid function.
Methods
The study population consisted of 586,460 adult Danish primary care patients (mean age, 50.2 years; 61% women) who underwent thyroid-function testing in Copenhagen between 2000 and 2010. Patients were followed until the end of 2010 or until they moved from the study area or died. Individuals with prevalent atrial fibrillation or treated thyroid dysfunction at baseline were excluded, as were patients with a history of amiodarone, digoxin, or vitamin K use. Information about comorbidities and mortality was obtained from national Danish registries. The primary outcome was new-onset atrial fibrillation, ascertained by inpatient International Classification of Diseases, 10th Revision (ICD-10) codes. Time-dependent Poisson regression analyses were adjusted for age, sex, calendar year, an index of comorbidities, and socioeconomic status. The reference range for serum TSH was 0.2 to 5.0 mIU/L. Individuals with serum TSH5.0 mIU/L and low FT4 were considered to have overt hypothyroidism and those with serum TSH >5.0 mIU/L and normal FT4 were considered to have subclinical hypothyroidism. Sensitivity analyses were performed to account for changes in both thyroid function and thyroid treatment status over time, with adjustment for atrial fibrillation risk factors including baseline history of hypertension, heart failure, myocardial infarction, valvular hear disease, and diabetes.
Results
At baseline, 96% of patients were euthyroid, 0.3% had overt hyperthyroidism, 2% had subclinical hyperthyroidism, 2% had subclinical hypothyroidism, and 0.7% had overt hypothyroidism. Individuals were followed for a mean of 5.5 years, over which time 17,154 (2.9%) were diagnosed with new atrial fibrillation while hospitalized. As compared with euthyroid individuals, the risk for atrial fibrillation was increased in patients with overt hyperthyroidism (adjusted incidence rate ratio [IRR], 1.41; 95% CI, 1.22 to 1.63) and patients with subclinical hyperthyroidism (IRR, 1.30; 95% CI ,1.18 to 1.43) as well as in individuals with high-normal thyroid function (defined as serum TSH 0.2 to 0.4 mIU/L with normal FT4; IRR, 1.12; 95% CI, 1.03 to 1.21). Risk for atrial fibrillation was found to be decreased in overt (IRR, 0.67; 95% CI, 0.50 to 0.92) and subclinical (IRR, 0.88; 95% CI, 0.79-0.97) hypothyroidism as compared with the euthyroid subjects. Sensitivity analyses did not substantially alter the results, although treatment of subclinical and overt hyperthyroidism was associated with a slight attenuation of atrial fibrillation risk.
Conclusions
This study demonstrates a linear inverse association between atrial fibrillation incidence and serum TSH. Even among euthyroid patients, lower serum TSH values were associated with a significantly increased risk for atrial fibrillation.
ANALYSIS AND COMMENTARY • • • • • •
A major strength of this study is its very large sample size. Important limitations include the potential for misclassification of outcomes given the limitations of ICD-10 codes and the fact that only in-hospital atrial fibrillation diagnoses were ascertained. Findings in this largely white and sociodemographically homogeneous population may not be generalizable to other settings. Information was not available regarding potentially important covariates such as body-mass index, smoking status, thyroid antibody status, serum lipid levels, and echocardiographic parameters. Future observational studies with more information about covariates could better characterize risk factors for atrial fibrillation among individuals with low serum TSH, although it is unlikely that larger samples will be studied in the future. Overall, further research is needed to determine the effects of treatment of subclinical hyperthyroidism on the risk for atrial fibrillation.
References
- Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D’Agostino RB. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994;331:1249-52.
- Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, Tracy RP, Ladenson PW. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033-41.
- Gammage MD, Parle JV, Holder RL, Roberts LM, Hobbs FD, Wilson S, Sheppard MC, Franklyn JA. Association between serum free thyroxine concentration and atrial fibrillation. Arch Intern Med 2007;167:928-34.
- Collet TH, Gussekloo J, Bauer DC, den Elzen WP, Cappola AR, Balmer P, Iervasi G, Åsvold BO, Sgarbi JA, Völzke H, et al. Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 2012;172:799-809.
- Heeringa J, Hoogendoorn EH, van der Deure WM, Hofman A, Peeters RP, Hop WC, den Heijer M, Visser TJ, Witteman JC. High-normal thyroid function and risk of atrial fibrillation: the Rotterdam study. Arch Intern Med 2008;168:2219-24.
CLINICAL THYROIDOLOGY • JANUARY 2013 VOLUME 25 • ISSUE 1 • © 2013
AMERICAN THYROID ASSOCIATION® , ATA® , THYROID® , CLINICAL THYROIDOLOGY® , and the distinctive circular logo are registered in the U.S. Patent and Trademark Office as trademarks of the American Thyroid Association® , Inc.