Sleep Disordered Breathing as a Risk of Cardiac Events in Subjects With Diabetes Mellitus and Normal Exercise Echocardiographic Findings Sinziana Seicean, MD, MPH, PhD a,b , Kingman P. Strohl, MD b,c , Andreea Seicean, MPH b , Conrad Gibby, BS b , and Thomas H. Marwick, MD, PhD, MPH a,d, * Sleep disordered breathing (SDB) is associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease; however, the contribution of SDB to incident heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF) in patients with T2DM is unknown. We followed up 834 consecutive asymptomatic patients with T2DM (age 56 – 11 years, 369 women) with normal exercise echocardiographic findings for £8 years using electronic health records. The demographics, cardiac risk factors, symptoms, diagnoses, and medications were collected at the echocardiography and validated from the electronic health records. SDB was confirmed by a comprehensive sleep evaluation and/or poly- somnography before echocardiography. SDB was diagnosed in 188 patients (21%) at baseline; 116 were untreated. During a median follow-up of 4.9 years (interquartile range 3.9 to 6.1), 22 congestive HF, 72 CAD, and 40 AF incident events were observed. In the Cox proportional hazards models, SDB was associated with incident CAD (hazard ratio 1.8, 95% confidence interval 1.1 to 3.0, p [ 0.01; adjusted hazard ratio 1.9, 95% confidence interval 1.2 to 3.2, p <0.01) and AF (hazard ratio 2.6, 95% confidence interval 1.4 to 4.7, p [ 0.01; adjusted hazard ratio 2.9, 95% confidence interval 1.5 to 5.9, p <0.01). Limiting SDB to only those patients diagnosed using polysomnography (n [ 132), SDB was asso- ciated with incident CAD (hazard ratio 1.9, 95% confidence interval 1.1 to 3.3, p [ 0.03; adjusted hazard ratio 2.2, 95% confidence interval 1.2 to 3.9, p [ 0.01) and HF (hazard ratio 2.7, 95% confidence interval 1.1 to 7.0, p [ 0.03; adjusted hazard ratio 3.5, 95% confidence interval 1.4 to 9.0, p <0.01). Female gender, age, elevated blood pressure, and left ventricular mass were additional correlates of CAD in those with asymptomatic T2DM. In conclusion, the association of SDB with incident CAD, AF, and HF in patients with T2DM justifies more liberal screening for SDB in patients with T2DM, realizing that SDB is a potentially modifiable risk factor. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:1214e1220) The prevalence of patients with type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the United States, involving 8.3% of the general population and 26.9% of patients aged 65 years. Adults with T2DM have a 2 to 4 times greater risk of heart disease-related mortality compared to their nondiabetic counterparts. 1 Sleep disor- dered breathing (SDB) has been associated with T2DM and impaired glucose tolerance, independent of other co- morbidities, including obesity. 2,3 Although a number of studies have assessed the association of SDB with cardio- vascular events, 4e13 none has focused on the effect of SDB on incident cardiovascular events in patients with asymp- tomatic T2DM without a history of cardiac disease. The aim of the present study was to define the role of SDB in inci- dent heart failure (HF), coronary artery disease (CAD), and atrial fibrillation (AF) in patients with T2DM without these diagnoses and without evidence of subclinical CAD at baseline. Methods The present study was a longitudinal observational study of adult patients with T2DM without a known cardiovascular history, who had been referred for stress echocardiography to rule out CAD, in the absence of cardiac symptoms. The most common cause for testing was a cardiac risk evaluation, mainly before noncardiac surgery. The day of the echocar- diogram was the entry date, and patients were followed up through October 31, 2011. Baseline data available from the Cleveland Clinic echocardiogram registry were supple- mented by abstraction from the electronic medical records and manual verification of the administrative and poly- somnography reports. The patient data were de-identified before statistical analyses. The institutional review board of Cleveland Clinic approved the study. a Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; b Case Western Reserve University, Cleveland, Ohio; c Louis Stokes Veterans Affairs Medical Center, Cleveland, Ohio; and d Menzies Research Institute of Tasmania, Hobart, Australia. Manuscript received September 20, 2012; revised manuscript received and accepted December 23, 2012. This work was partially supported through grants HL007913 and HS00059-14 from the National Institutes of Health (Bethesda, Maryland). See page 1220 for disclosure information. *Corresponding author: Tel: (þ61) 36-226-7703; fax: (þ61) 36-226- 7704. E-mail address: tom.marwick@utas.edu.au (T.H. Marwick). 0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. www.ajconline.org http://dx.doi.org/10.1016/j.amjcard.2012.12.053