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Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.
Circulation. 2017 Nov 28; 136(22):2100-2116.Circ

Abstract

BACKGROUND

Atrial 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.

METHODS

We 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.

RESULTS

Of 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.

CONCLUSIONS

In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

Authors+Show Affiliations

Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.).Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.). University of Bern, Switzerland; Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Institue of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada (B.R.d.C.).Service of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne, Switzerland (T.-H.C.).Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.). Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.).Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.).Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco (D.C.B.).University of Pennsylvania School of Medicine, Philadelphia (A.R.C.).Department of Epidemiology, University of Washington, Seattle (S.R.H.).Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Italy (G.C.).Department of Public Health and Primary Care, and Department of Gerontology and Geriatrics (J.G.).Department of Clinical Chemistry and Laboratory Medicine (W.P.J.d.E.).Leiden University Medical Center, The Netherlands; Departments of Internal Medicine and Epidemiology (R.P.P.).Erasmus Medical Center, Rotterdam, The Netherlands; Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, United Kingdom (R.L., K.-T.K.).Institute for Community Medicine, Clinical-Epidemiological Research (H.V.).Department of Internal Medicine (M.D.).University Medicine Greifswald, Germany, and German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany; School of Medicine and Pharmacology, University of Western Australia, Crawley, Australia (J.P.W.). Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia (J.P.W.).School of Population Health, University of Western Australia, Crawley, Australia (A.B.).Cardiology Unit, Department of Emergency and Organ Transplantation, University of Bari, Italy (M.I.).Institute of Health and Wellbeing (P.M.).Department of Epidemiology and Biostatistics (J.H.).Institute of Cardiovascular and Medical Sciences, (D.J.S.).University of Glasgow, United Kingdom; Department of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark (R.G.J.W.).Erasmus Medical Center, Rotterdam, The Netherlands; Department of Public Health and Primary Care, University of Cambridge, Addenbrooke's Hospital, United Kingdom (R.L., K.-T.K.).Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, PA (J.W.M.).Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.).Department of General Internal Medicine, Inselspital, Bern University Hospital, (C.B., M.F., C.F., D.A., N.R.) Nicolas.Rodondi@insel.ch. Institute of Primary Health Care (BIHAM) (B.R.d.C., M.F., N.R.).No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

29061566

Citation

Baumgartner, Christine, et al. "Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation." Circulation, vol. 136, no. 22, 2017, pp. 2100-2116.
Baumgartner C, da Costa BR, Collet TH, et al. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation. 2017;136(22):2100-2116.
Baumgartner, C., da Costa, B. R., Collet, T. H., Feller, M., Floriani, C., Bauer, D. C., Cappola, A. R., Heckbert, S. R., Ceresini, G., Gussekloo, J., den Elzen, W. P. J., Peeters, R. P., Luben, R., Völzke, H., Dörr, M., Walsh, J. P., Bremner, A., Iacoviello, M., Macfarlane, P., ... Rodondi, N. (2017). Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation, 136(22), 2100-2116. https://doi.org/10.1161/CIRCULATIONAHA.117.028753
Baumgartner C, et al. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation. 2017 Nov 28;136(22):2100-2116. PubMed PMID: 29061566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. AU - Baumgartner,Christine, AU - da Costa,Bruno R, AU - Collet,Tinh-Hai, AU - Feller,Martin, AU - Floriani,Carmen, AU - Bauer,Douglas C, AU - Cappola,Anne R, AU - Heckbert,Susan R, AU - Ceresini,Graziano, AU - Gussekloo,Jacobijn, AU - den Elzen,Wendy P J, AU - Peeters,Robin P, AU - Luben,Robert, AU - Völzke,Henry, AU - Dörr,Marcus, AU - Walsh,John P, AU - Bremner,Alexandra, AU - Iacoviello,Massimo, AU - Macfarlane,Peter, AU - Heeringa,Jan, AU - Stott,David J, AU - Westendorp,Rudi G J, AU - Khaw,Kay-Tee, AU - Magnani,Jared W, AU - Aujesky,Drahomir, AU - Rodondi,Nicolas, AU - ,, Y1 - 2017/10/23/ PY - 2017/04/03/received PY - 2017/08/31/accepted PY - 2017/10/25/pubmed PY - 2017/12/5/medline PY - 2017/10/25/entrez KW - atrial fibrillation KW - hypothyroidism KW - thyrotropin KW - thyroxine SP - 2100 EP - 2116 JF - Circulation JO - Circulation VL - 136 IS - 22 N2 - BACKGROUND: Atrial 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. METHODS: We 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. RESULTS: Of 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. CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/29061566/Thyroid_Function_Within_the_Normal_Range_Subclinical_Hypothyroidism_and_the_Risk_of_Atrial_Fibrillation_ DB - PRIME DP - Unbound Medicine ER -