Thyroid Disease and Risk of New Onset Atrial Fibrillation
Thyroid Disease and Risk of New Onset Atrial Fibrillation
Objectives To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients.
Design Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level.
Setting Primary care patients in the city of Copenhagen.
Subjects Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation.
Main outcome measure Poisson regression models used to estimate risk of atrial fibrillation by thyroid function.
Results Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation.
Conclusion The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.
Atrial fibrillation is a common cardiac arrhythmia and an important risk factor for ischaemic stroke and heart failure. Thyroid hormones have substantial effects on the cardiovascular system, and it is well known that overt hyperthyroidism is associated with atrial fibrillation. Subclinical hyperthyroidism (that is, reduced serum thyroid stimulating hormone (TSH) concentration but free thyroxine levels within reference ranges) is associated with elevated resting pulse, increased frequency of atrial and ventricular premature beats, increased left ventricular mass index, and cardiac output. Previous studies of subclinical hyperthyroidism have suggested increased risk of developing atrial fibrillation, but these studies were all performed in relatively small cohorts or using pooled data from several small cohorts. Also, because of the small sample sizes, it has been difficult to characterise subgroups of patients with subclinical hyperthyroidism in order to assess a possible “dose dependent” association between serum TSH concentration and risk of atrial fibrillation, sex differences, and the possible role of high normal thyroid function (low TSH within the normal reference range). How subclinical hyperthyroidism should be managed has therefore also been much debated.
Overt hypothyroidism, however, is associated with bradycardia, dyslipidaemia, hypertension, atherosclerosis, decreased variability in heart rate, and increased risk of myocardial infarction. Imaging studies of patients with subclinical hypothyroidism (that is, with increased TSH, but free thyroxine within reference range) have shown subtle changes in cardiac performance. Despite these observations, neither overt nor subclinical hypothyroidism has been associated with increased or decreased risk of atrial fibrillation.
The prevalence of subclinical thyroid dysfunction is high in the adult population, and symptoms of thyroid disease are often mild—and, therefore, thyroid functions tests are often performed routinely in primary care on vague clinical indications. Furthermore, thyroid testing is typically included in many standard laboratory test packages. This policy makes available large population based databases with thyroid test results. Patients followed in primary care are often more healthy than hospital patients (inpatients and outpatients) and therefore provide a unique possibility to assess the isolated effect of thyroid dysfunction on the development of atrial fibrillation. The purpose of the present study was to assess the relation between thyroid function and risk of atrial fibrillation in a large cohort of primary care patients.
Abstract and Introduction
Abstract
Objectives To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients.
Design Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level.
Setting Primary care patients in the city of Copenhagen.
Subjects Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation.
Main outcome measure Poisson regression models used to estimate risk of atrial fibrillation by thyroid function.
Results Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation.
Conclusion The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.
Introduction
Atrial fibrillation is a common cardiac arrhythmia and an important risk factor for ischaemic stroke and heart failure. Thyroid hormones have substantial effects on the cardiovascular system, and it is well known that overt hyperthyroidism is associated with atrial fibrillation. Subclinical hyperthyroidism (that is, reduced serum thyroid stimulating hormone (TSH) concentration but free thyroxine levels within reference ranges) is associated with elevated resting pulse, increased frequency of atrial and ventricular premature beats, increased left ventricular mass index, and cardiac output. Previous studies of subclinical hyperthyroidism have suggested increased risk of developing atrial fibrillation, but these studies were all performed in relatively small cohorts or using pooled data from several small cohorts. Also, because of the small sample sizes, it has been difficult to characterise subgroups of patients with subclinical hyperthyroidism in order to assess a possible “dose dependent” association between serum TSH concentration and risk of atrial fibrillation, sex differences, and the possible role of high normal thyroid function (low TSH within the normal reference range). How subclinical hyperthyroidism should be managed has therefore also been much debated.
Overt hypothyroidism, however, is associated with bradycardia, dyslipidaemia, hypertension, atherosclerosis, decreased variability in heart rate, and increased risk of myocardial infarction. Imaging studies of patients with subclinical hypothyroidism (that is, with increased TSH, but free thyroxine within reference range) have shown subtle changes in cardiac performance. Despite these observations, neither overt nor subclinical hypothyroidism has been associated with increased or decreased risk of atrial fibrillation.
The prevalence of subclinical thyroid dysfunction is high in the adult population, and symptoms of thyroid disease are often mild—and, therefore, thyroid functions tests are often performed routinely in primary care on vague clinical indications. Furthermore, thyroid testing is typically included in many standard laboratory test packages. This policy makes available large population based databases with thyroid test results. Patients followed in primary care are often more healthy than hospital patients (inpatients and outpatients) and therefore provide a unique possibility to assess the isolated effect of thyroid dysfunction on the development of atrial fibrillation. The purpose of the present study was to assess the relation between thyroid function and risk of atrial fibrillation in a large cohort of primary care patients.
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