{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:53:12Z","timestamp":1789523592751,"version":"build-2803163510"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Thyroid hormones act on the cardiovascular system directly by modulating its function and indirectly by transcriptional regulation of gene expression in the heart and the vasculature. Studies have shown associations between overt and subclinical thyroid disorders and cardiovascular outcomes. The aim of this study was to perform a systematic review and meta-analysis to assess the potential relationships between subclinical hyper- and hypothyroidism and risk of atrial fibrillation (AF), and post-operative AF.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>MEDLINE and Scopus databases were searched from inception to 18<jats:sup>th<\/jats:sup> February 2023 for randomised controlled trials, case-control studies, and cohort studies which assessed the relationship between subclinical thyroid dysfunction and incident AF events. Risk of bias and the quality of evidence were assessed using the RoBANS tool and GRADE approach, respectively. Meta-analysis was conducted in Review Manager 5.4 using the Mantel-Haenszel statistical method and a random-effects model. Data are presented as risk ratios with 95% confidence intervals. Statistical heterogeneity amongst studies was assessed by the chi-squared (\u03c7<jats:sup>2<\/jats:sup>) test and <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> statistic. <jats:italic>p<\/jats:italic>\u22640.05 were considered significant.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 6467 records were identified, of which 10 cohort studies met the inclusion criteria. Both subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of incident AF (risk ratio (RR), 1.99; 95% confidence interval (CI), 1.43\u20132.77; n = 5 studies; <jats:italic>p<\/jats:italic>&lt;0.0001 and RR, 1.19; CI, 1.03\u20131.39; n = 7 studies; <jats:italic>p<\/jats:italic> = 0.02, respectively). Subgroup analysis for post-operative AF revealed marked heterogeneity between studies (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 84%) and association with subclinical hypothyroidism was not significant (RR, 1.41; CI, 0.89\u20132.22; n = 3 studies; <jats:italic>p<\/jats:italic> = 0.15).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The current evidence suggests that both subclinical hyperthyroidism and subclinical hypothyroidism are associated with increased risk of incident AF. Further investigation is required to determine potential causal links that would guide future clinical practice.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0296413","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T19:21:35Z","timestamp":1704223295000},"page":"e0296413","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Subclinical thyroid dysfunction and the risk of incident atrial fibrillation: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"19","author":[{"given":"Hasveer","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam Z.","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-9378","authenticated-orcid":true,"given":"Deirdre A.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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Thyroid disease: assessment and management. NICE guidance. 2019 [cited 2023 August 22]. https:\/\/www.nice.org.uk\/guidance\/ng145\/chapter\/Recommendations."},{"issue":"5","key":"pone.0296413.ref010","doi-asserted-by":"crossref","first-page":"e2211863","DOI":"10.1001\/jamanetworkopen.2022.11863","article-title":"Association of thyroid hormone treatment intensity with cardiovascular mortality among US veterans","volume":"5","author":"JM Evron","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"10","key":"pone.0296413.ref011","doi-asserted-by":"crossref","first-page":"e3890","DOI":"10.1210\/clinem\/dgab444","article-title":"Thyroid hormone therapy and incident stroke","volume":"106","author":"M Papaleontiou","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"pone.0296413.ref012","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/ehjqcco\/qcaa061","article-title":"Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990\u20132017: results from the global burden of disease study 2017","volume":"7","author":"H Dai","year":"2021","journal-title":"Eur Heart J Qual Care Clin Outcomes"},{"issue":"20","key":"pone.0296413.ref013","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1001\/jama.2011.659","article-title":"Risk of death and cardiovascular events in initially healthy women with new-onset atrial fibrillation","volume":"305","author":"D Conen","year":"2011","journal-title":"JAMA"},{"issue":"2","key":"pone.0296413.ref014","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1161\/01.STR.28.2.316","article-title":"Atrial fibrillation and dementia in a population-based study. The rotterdam study","volume":"28","author":"A Ott","year":"1997","journal-title":"Stroke"},{"issue":"5","key":"pone.0296413.ref015","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0002-9343(02)01236-6","article-title":"A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the renfrew\/paisley study","volume":"113","author":"S Stewart","year":"2002","journal-title":"Am J Med"},{"issue":"10","key":"pone.0296413.ref016","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1212\/WNL.28.10.973","article-title":"Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the framingham study","volume":"28","author":"PA Wolf","year":"1978","journal-title":"Neurology"},{"issue":"3","key":"pone.0296413.ref017","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/0003-4975(93)90894-N","article-title":"Hazards of postoperative atrial arrhythmias","volume":"56","author":"LL Creswell","year":"1993","journal-title":"Ann Thorac Surg"},{"issue":"7","key":"pone.0296413.ref018","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41569-019-0166-5","article-title":"Postoperative atrial fibrillation: mechanisms, manifestations and management","volume":"16","author":"D Dobrev","year":"2019","journal-title":"Nat Rev Cardiol"},{"issue":"4","key":"pone.0296413.ref019","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1097\/00000658-199710000-00011","article-title":"Atrial fibrillation after cardiac surgery: a major morbid event?","volume":"226","author":"G Hossein Almassi","year":"1997","journal-title":"Ann Surg"},{"issue":"12","key":"pone.0296413.ref020","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1001\/jama.2010.1361","article-title":"Subclinical hypothyroidism and the risk of coronary heart disease and mortality","volume":"304","author":"N Rodondi","year":"2010","journal-title":"JAMA"},{"issue":"4","key":"pone.0296413.ref021","doi-asserted-by":"crossref","first-page":"270","DOI":"10.7326\/0003-4819-132-4-200002150-00004","article-title":"Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the rotterdam study","volume":"132","author":"AE Hak","year":"2000","journal-title":"Ann Intern Med"},{"issue":"9","key":"pone.0296413.ref022","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1161\/CIRCULATIONAHA.112.096024","article-title":"Subclinical thyroid dysfunction and the risk of heart failure events","volume":"126","author":"B Gencer","year":"2012","journal-title":"Circulation"},{"issue":"4","key":"pone.0296413.ref023","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.jclinepi.2012.09.016","article-title":"Testing a tool for assessing the risk of bias for nonrandomized studies showed moderate reliability and promising validity","volume":"66","author":"SY Kim","year":"2013","journal-title":"J Clin Epidemiol"},{"issue":"4","key":"pone.0296413.ref024","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jclinepi.2010.07.015","article-title":"GRADE guidelines: 3. Rating the quality of evidence","volume":"64","author":"H Balshem","year":"2011","journal-title":"J Clin Epidemiol"},{"key":"pone.0296413.ref025","unstructured":"GRADEpro GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2022. gradepro.org."},{"key":"pone.0296413.ref026","unstructured":"Review Manager (RevMan) [Computer Program]. Version 5.4, The Cochrane Collaboration, 2020."},{"key":"pone.0296413.ref027","unstructured":"Deeks J, Higgins J, Altman D. Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023): Cochrane, 2023; www.training.cochrane.org\/handbook."},{"issue":"3","key":"pone.0296413.ref028","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2796.1990.tb00223.x","article-title":"Is a more active attitude warranted in patients with subclinical thyrotoxicosis?","volume":"228","author":"A Tenerz","year":"1990","journal-title":"J Intern Med"},{"issue":"9","key":"pone.0296413.ref029","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/jama.295.9.1033","article-title":"Thyroid status, cardiovascular risk, and mortality in older adults","volume":"295","author":"AR Cappola","year":"2006","journal-title":"JAMA"},{"issue":"6","key":"pone.0296413.ref030","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.athoracsur.2009.03.032","article-title":"Subclinical hypothyroidism might increase the risk of transient atrial fibrillation after coronary artery bypass grafting","volume":"87","author":"YJ Park","year":"2009","journal-title":"Ann Thorac Surg"},{"issue":"5","key":"pone.0296413.ref031","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/j.1365-2265.2009.03696.x","article-title":"Natural history of subclinical hyperthyroidism in elderly patients with TSH between 0.1 and 0.4 mIU\/l: a prospective study","volume":"72","author":"PW Rosario","year":"2010","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"6","key":"pone.0296413.ref032","first-page":"277","article-title":"A retrospective study of the natural history of endogenous subclinical hyperthyroidism","volume":"110","author":"R Poola","year":"2011","journal-title":"WMJ"},{"issue":"3","key":"pone.0296413.ref033","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1210\/jc.2011-1978","article-title":"Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk","volume":"97","author":"D Nanchen","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"pone.0296413.ref034","doi-asserted-by":"crossref","first-page":"e7895","DOI":"10.1136\/bmj.e7895","article-title":"The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study","volume":"345","author":"C Selmer","year":"2012","journal-title":"BMJ"},{"issue":"5","key":"pone.0296413.ref035","first-page":"427","article-title":"Subclinical hypothyroidism might increase the risk of postoperative atrial fibrillation after aortic valve replacement","volume":"64","author":"J Mart\u00ednez-Comendador","year":"2016","journal-title":"Thorac Cardiovasc surg"},{"issue":"1","key":"pone.0296413.ref036","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/cen.13472","article-title":"Thyroid-stimulating hormone and risk of sudden cardiac death, total mortality and cardiovascular morbidity","volume":"88","author":"VL Lang\u00e9n","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"4","key":"pone.0296413.ref037","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1111\/jocs.15395","article-title":"Impact of subclinical hypothyroidism on outcomes of coronary bypass surgery","volume":"36","author":"D Zhao","year":"2021","journal-title":"J Card Surg"},{"key":"pone.0296413.ref038","unstructured":"British thyroid foundation. Thyroid function tests 2021 [cited 2023 August 22]. https:\/\/www.btf-thyroid.org\/thyroid-function-tests."},{"key":"pone.0296413.ref039","first-page":"8130796","article-title":"Relationship between subclinical thyroid dysfunction and the risk of cardiovascular outcomes: a systematic review and meta-analysis of prospective cohort studies","volume":"2017","author":"J Sun","year":"2017","journal-title":"Int J Endocrinol"},{"issue":"10","key":"pone.0296413.ref040","first-page":"799","article-title":"Subclinical hyperthyroidism and the risk of coronary heart disease and mortality","volume":"172","author":"T-H Collet","year":"2012","journal-title":"Arch Intern Med"},{"issue":"11","key":"pone.0296413.ref041","first-page":"A12190701","article-title":"Subclinical hyperthyroidism and the risk of developing cardiovascular disease-a systematic review","volume":"67","author":"SB Smedegaard","year":"2020","journal-title":"Dan Med J"},{"issue":"22","key":"pone.0296413.ref042","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1161\/CIRCULATIONAHA.117.028753","article-title":"Thyroid function within the normal range, subclinical hypothyroidism, and the risk of atrial fibrillation","volume":"136","author":"C Baumgartner","year":"2017","journal-title":"Circulation"},{"issue":"6","key":"pone.0296413.ref043","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.ejcts.2009.12.033","article-title":"Postoperative atrial fibrillation in patients undergoing aortocoronary bypass surgery carries an eightfold risk of future atrial fibrillation and a doubled cardiovascular mortality","volume":"37","author":"A Ahlsson","year":"2010","journal-title":"Eur J Cardiothorac Surg"},{"issue":"4","key":"pone.0296413.ref044","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S1010-7940(03)00396-8","article-title":"Free triiodothyronine: a novel predictor of postoperative atrial fibrillation","volume":"24","author":"AG Cerillo","year":"2003","journal-title":"Eur J Cardiothorac Surg"},{"issue":"3","key":"pone.0296413.ref045","doi-asserted-by":"crossref","first-page":"c214","DOI":"10.1159\/000235241","article-title":"Cohort studies: Prospective versus retrospective","volume":"113","author":"AM Euser","year":"2009","journal-title":"Nephron Clin Pract"},{"issue":"1","key":"pone.0296413.ref046","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1053\/j.jvca.2021.08.060","article-title":"The importance of thyroid hormone levels after heart surgery-preliminary study","volume":"35","author":"B Sz\u00e9csi","year":"2021","journal-title":"J Cardiothorac Vasc Anesth"},{"issue":"5","key":"pone.0296413.ref047","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/0003-4975(96)00102-6","article-title":"Triiodothyronine therapy lowers the incidence of atrial fibrillation after cardiac operations","volume":"61","author":"JD Klemperer","year":"1996","journal-title":"Ann Thorac Surg"},{"issue":"6","key":"pone.0296413.ref048","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/S0022-5223(99)70249-7","article-title":"A randomized double-blind study of the effect of triiodothyronine on cardiac function and morbidity after coronary bypass surgery","volume":"117","author":"SL Mullis-Jansson","year":"1999","journal-title":"J Thorac Cardiovasc Surg"},{"issue":"1","key":"pone.0296413.ref049","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/europace\/euac144","article-title":"Searching for atrial fibrillation: looking harder, looking longer, and in increasingly sophisticated ways. 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