CENTRAL ILLUSTRATION Assessing Which Characteristics of Diabetes Are Associated With Ischemic Stroke in Patients With Atrial Fibrillation Increased duration of diabetes Potential mechanisms : Enhanced thrombin generation Impaired fibrinolysis with prolonged lysis time Patient with atrial fibrillatio

Fro Sch xD an Sch for Wa Bo Na Ma tat con Joh BACKGROUND Diagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF). OBJECTIVES The purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF. METHODS We assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes ($3 years compared with <3 years) and HbA1c values ($9.0% and 7.0% to 8.9% compared with <7.0%), focusing on periods where patients were not anticoagulated. RESULTS There were 2,101 diabetic patients included in the duration analysis: 40% with duration <3 years and 60% with duration $3 years at baseline. Among 1,933 diabetic patients included in the HbA1c analysis, 46% had HbA1c<7.0%, 36% between 7.0% and 8.9%, and 19%$9.0% at baseline. Duration of diabetes$3 years was associated with an increased rate of ischemic stroke compared with duration <3 years (adjusted hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.10 to 2.76). The increased stroke rate was observed in older (age $75 years) and younger (age <75 years) individuals. Neither poor glycemic control (HbA1c $9.0%, adjusted HR: 1.04, 95% CI: 0.57 to 1.92) nor moderately increased HbA1c (7.0% to 8.9%, adjusted HR: 1.21, 95% CI: 0.77 to 1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had HbA1c <7.0%. CONCLUSIONS Duration of diabetes is a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and AF. (J Am Coll Cardiol 2016;67:239–47) © 2016 by the American College of Cardiology Foundation. m the *Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts; yHarvard Medical ool, Boston, Massachusetts; zEpidemiology Department, Boston University School of Public Health, Boston, Massachusetts; ivision of Research, Kaiser Permanente Northern California, Oakland, California; kDepartment of Epidemiology, Biostatistics d Medicine, University of California, San Francisco, California; {Department of Health Research and Policy, Stanford University ool of Medicine, Stanford, California; #Department of Medicine, University of California, San Francisco, San Francisco, Calinia; **Department of Environmental and Occupational Health, School of Public Health and Health Services, The George shington University, Washington, DC; and the yyDepartment of Environmental Health, Harvard School of Public Health, ston, Massachusetts. This study was supported by the National Institute on Aging (R01 AG15478 and K23 AG028978), the tional Heart, Lung, and Blood Institute (U19 HL91179 and RC2HL101589), and the Eliot B. and Edith C. Shoolman fund of the ssachusetts General Hospital. The funding sources had no role in study design, data collection, data analysis, data interpreion, or preparation of the manuscript. Dr. Go has received a research grant from iRhythm and CSL Behring. Dr. Singer serves as a sultant/advisory board member for Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, CVS Heath, Johnson & nson, Medtronic, Pfizer, and St. Jude Medical on matters related to preventing stroke in atrial fibrillation; and has research ABBR EV I A T I ON S