• Christine Baumgartner, Bruno R da Costa, Tinh-Hai Collet, Martin Feller, Carmen Floriani, Douglas C Bauer, Anne R Cappola, Susan R Heckbert, Graziano Ceresini, Jacobijn Gussekloo, den ElzenWendy P JWPJDepartment of Clinical Chemistry and Laboratory Medicine (W.P.J.d.E.)., Robin P Peeters, Robert Luben, Henry Völzke, Marcus Dörr, John P Walsh, Alexandra Bremner, Massimo Iacoviello, Peter Macfarlane, Jan Heeringa, David J Stott, WestendorpRudi G JRGJUniversity of Glasgow, United Kingdom; Department of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark (R.G.J.W.)., Kay-Tee Khaw, Jared W Magnani, Drahomir Aujesky, Nicolas Rodondi, and Thyroid Studies Collaboration.
• Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.).
• Circulation. 2017 Nov 28; 136 (22): 2100-2116.

BackgroundAtrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.MethodsWe conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.ResultsOf 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.ConclusionsIn euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.© 2017 American Heart Association, Inc.

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