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      New-Onset Atrial Fibrillation Is a Predictor of Subsequent Hyperthyroidism: A Nationwide Cohort Study

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          Abstract

          Aims

          To examine the long-term risk of hyperthyroidism in patients admitted to hospital with new-onset AF. Hyperthyroidism is a well-known risk factor for atrial fibrillation (AF), but it is unknown whether new-onset AF predicts later-occurring hyperthyroidism.

          Methods and Results

          All patients admitted with new-onset AF in Denmark from 1997–2009, and their present and subsequent use of anti-thyroid medication was identified by individual-level linkage of nationwide registries. Patients with previous thyroid diagnosis or thyroid medication use were excluded. Development of hyperthyroidism was assessed as initiation of methimazole or propylthiouracil up to a 13-year period. Risk of hyperthyroidism was analysed by Poisson regression models adjusted for important confounders such as amiodarone treatment. Non-AF individuals from the general population served as reference. A total of 145,623 patients with new-onset AF were included (mean age 66.4 years [SD ±13.2] and 55.3% males) of whom 3% (4,620 events; 62.2% women) developed hyperthyroidism in the post-hospitalization period compared to 1% (48,609 events; 82% women) in the general population (n = 3,866,889). In both women and men we found a significantly increased risk of hyperthyroidism associated with new-onset AF compared to individuals in the general population. The highest risk was found in middle-aged men and was consistently increased throughout the 13-year period of observation. The results were confirmed in a substudy analysis of 527,352 patients who had thyroid screening done.

          Conclusion

          New-onset AF seems to be a predictor of hyperthyroidism. Increased focus on subsequent risk of hyperthyroidism in patients with new-onset AF is warranted.

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          Most cited references27

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          The clinical significance of subclinical thyroid dysfunction.

          Subclinical thyroid disease (SCTD) is defined as serum free T(4) and free T(3) levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and cardiovascular risk. Here, we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.
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            Rhythm control versus rate control for atrial fibrillation and heart failure.

            It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.) 2008 Massachusetts Medical Society
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              The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study.

              Atrial fibrillation is a common arrhythmia associated with increased cardiovascular morbidity and mortality. This study was undertaken to identify the natural history of this condition, including risk factors for its development, and outcome. The incidence of atrial fibrillation among 3,983 male air crew recruits observed continuously for 44 years was calculated based on person-years of observation. Age and 23 variables were examined to identify risk factors for atrial fibrillation. Controlling for age and 9 prognostic variables, the effect of atrial fibrillation on 8 outcomes was examined. Analysis of risk factors for atrial fibrillation and outcome after atrial fibrillation was based on a Cox proportional hazard model using time-dependent covariates. Of the 3,983 study members, 299 (7.5%) developed atrial fibrillation during 154,131 person-years of observation. The incidence rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70. Risk for atrial fibrillation was increased with myocardial infarction (relative risk [RR] 3.62), angina (RR 2.84), and ST-T wave abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for atrial fibrillation was strongest at the onset of ischemic heart disease and diminished over time. The rate of atrial fibrillation was 1.42 times increased in men with a history of hypertension. Congestive heart failure, valvular heart disease, and cardiomyopathy were important but uncommon risk factors. Atrial fibrillation independently increased the risk for stroke (RR 2.07) and congestive heart failure (RR 2.98). Total mortality rate was increased 1.31 times; cardiovascular mortality including and excluding fatal stroke were also increased (RR 1.41 and 1.37, respectively). The incidence of atrial fibrillation in men increases with advancing age. Clinical cardiac abnormalities, particularly recent ischemic heart disease and hypertension, are strongly associated with increased risk for atrial fibrillation. Atrial fibrillation increases morbidity and mortality, but the magnitude of the increase may be less than previously reported.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                28 February 2013
                : 8
                : 2
                : e57893
                Affiliations
                [1 ]Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark
                [2 ]Department of Cardiology, Roskilde University Hospital, Roskilde, Denmark
                [3 ]Department of Endocrinology, Herlev University Hospital, Herlev, Denmark
                [4 ]Copenhagen General Practitioners Laboratory, Copenhagen, Denmark
                Medical University Innsbruck, Austria
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CS JBO JL ODP GHG. Performed the experiments: CS JBO JL AMSC CTP GHG. Analyzed the data: CS CM US JF PRH. Contributed reagents/materials/analysis tools: JCM CTP GHG JL JBO MLH. Wrote the paper: CS JBO JF ODP GHG.

                Article
                PONE-D-12-31660
                10.1371/journal.pone.0057893
                3585274
                23469097
                24868a15-b653-41e8-9941-8e7298e5696c
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 October 2012
                : 28 January 2013
                Page count
                Pages: 9
                Funding
                The study was funded in part by unrestricted grants from the The Danish Heart Foundation (Ref. no. 11-04-R84-A3483-22669), The Danish Thyroid Association, The Agnes and Knut Mørk Foundation, and the FUKAP and START Foundations, Gentofte University Hospital, Denmark. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Population Biology
                Epidemiology
                Medicine
                Cardiovascular
                Acute Cardiovascular Problems
                Arrhythmias
                Electrophysiology
                Clinical Research Design
                Cohort Studies
                Epidemiology
                Endocrinology
                Thyroid
                Graves' Disease
                Epidemiology
                Cardiovascular Disease Epidemiology
                Clinical Epidemiology

                Uncategorized
                Uncategorized

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