The association of asthma and atrial fibrillation — A nationwide population-based nested case–control study Wan-Leong Chan a,b,c, ⁎, Kun-Pin Yang b , Tze-Fan Chao b , Chin-Chou Huang b,c,e,f , Po-Hsun Huang b,c,g , Yu-Chun Chen d,h , Tzeng-Ji Chen d,h , Shing-Jong Lin b,c,g , Jaw-Wen Chen b,c,f , Hsin-Bang Leu a,b,c,e,f a Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan b Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan c Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan d Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan e Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan f Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan g Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan h Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan abstract article info Article history: Received 2 May 2012 Received in revised form 21 July 2014 Accepted 26 July 2014 Available online 1 August 2014 Keywords: Atrial fibrillation Asthma Corticosteroid Population-based nested case–control study Background: Asthma and atrial fibrillation (AF) have been reported to be related to an increased risk of cardiovas- cular events. However, the relationship between asthma and AF has not been fully elucidated. The purpose of this study was to examine the association between asthma and AF risk. Methods: We conducted a population-based nested case–control study including a total of 7439 newly-diagnosed adult patients with AF and 10,075 age-, gender-, comorbidity-, and cohort entry date-matched subjects without AF from the Taiwan National Health Insurance database. Exposure to asthma as well as medications including bronchodilators and corticosteroid before the index date was evaluated to investigate the association between AF and asthma as well as concurrent medications. Results: AF patients were 1.2 times (adjusted OR 1.2, 95% CI 1.109–1.298) more likely to be associated with a future occurrence of asthma independent of comorbidities and treatment with corticosteroids and bronchodila- tor. In addition, the risks of new-onset AF were significantly higher among current users of inhaled corticosteroid, oral corticosteroids, and bronchodilators. Newly users (within 6 months) have the highest risk (inhaled cortico- steroid: OR, 2.13; 95% CI, 1.226–3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P b 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P b 0.001). A graded association with AF risk was also observed among subjects treated with corticosteroid (inhaled and systemic administration) and bronchodi- lators. New users (within 6 months) of these medications had the highest risk of AF (ICS: OR, 2.13; 95% CI, 1.226– 3.701, P = 0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66–2.25, P b 0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48–3.273, P b 0.001). A graded association with AF risk was also observed among subjects treated with ICS or bronchodilator. Conclusions: Asthma was associated with an increased risk of developing future AF. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia and is associated with marked morbidity, mortality and medical burden [1]. The lifetime risk for the development of AF is approximately 25% in the general population [2]. An association be- tween AF and total mortality (1.5–1.9 fold increase) and stroke (5-fold increase) has also been reported in the Framingham Heart Study [3,4]. Cardiovascular diseases such as coronary artery disease (CAD), valvular heart disease, hypertension, and congestive heart failure have also been associated with the occurrence of AF; however, the pathophysiology of AF remains incompletely understood. In addition to hemodynamic stress, etiologies such as atrial ischemia, autonomic imbalance, and neurohormonal activation have been identified as possible mechanisms of AF. Additionally, inflammation and oxidative stress have been impli- cated in the pathogenesis of AF. Aviles et al. demonstrated that elevated C-reactive protein (CRP) level, a systemic marker of inflammation, was predictive of AF incidence [5]. Furthermore, Schnabel et al. demonstrat- ed that subjects with elevated CRP had an additional 25% increased risk International Journal of Cardiology 176 (2014) 464–469 ⁎ Corresponding author at: Healthcare and Management Center, Division of Cardiology, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, Taiwan. Tel.: +886 2 2871 2121x3424; fax: +886 2 2875 7735. E-mail address: wlchan@vghtpe.gov.tw (W.-L. Chan). http://dx.doi.org/10.1016/j.ijcard.2014.07.087 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard