title: Duration of Diabetes Mellitus and Risk of Thromboembolism and Bleeding in Atrial Fibrillation: Nationwide Cohort Study.
abstract: OBJECTIVE
  Guidelines advocate anticoagulant treatment to all patients with atrial fibrillation and concomitant diabetes mellitus. The potential refinement to thromboembolic risk stratification that may spring from subdividing diabetes mellitus is unexplored. The purpose was to investigate duration of diabetes mellitus as a predictor of thromboembolism and anticoagulant-related bleeding in patients with atrial fibrillation.
  
  
  METHODS
  Using nationwide Danish registries, we identified all patients discharged from hospital with an incident diagnosis of atrial fibrillation from 2000 to 2011. Hazard ratios with 95% confidence intervals for thromboembolism and bleeding according to years of diabetes mellitus duration in categories (0-4, 5-9, 10-14, and ≥15) and as a continuous variable using cubic splines were calculated by Cox regression.
  
  
  RESULTS
  The study population comprised 137 222 patients with atrial fibrillation, of which 12.4% had diabetes mellitus. Compared with patients without diabetes mellitus and after adjustment for anticoagulant treatment and CHA2DS2-VASc components (congestive heart failure, hypertension, age, previous stroke, vascular disease, and sex), the risk of thromboembolism was lowest in the 0 to 4 years duration category (hazard ratio, 1.11; 95% confidence interval, 1.03-1.20), and highest in the longest duration category of ≥15 years (hazard ratio, 1.48; 95% confidence interval, 1.29-1.70). When analyzed as a continuous variable, duration of diabetes mellitus was associated with risk of thromboembolism in a dose-response-dependent manner, but not with a higher risk of bleeding during anticoagulant treatment.
  
  
  CONCLUSIONS
  In patients with atrial fibrillation, longer duration of diabetes mellitus was associated with a higher risk of thromboembolism, but not with a higher risk of anticoagulant-related bleeding. Considering the critical balance between preventing thromboembolism and avoiding bleeding, longer duration of diabetes mellitus may favor initiation of anticoagulant therapy.
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Thure Filskov
authors.initials: TF
authors.lastname: Overvad
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Flemming
authors.initials: F
authors.lastname: Skjøth
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Lane
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Ida Ehlers
authors.initials: IE
authors.lastname: Albertsen
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.).
authors.forename: Lars Hvilsted
authors.initials: LH
authors.lastname: Rasmussen
authors.affiliation: From the Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark (T.F.O., F.S., G.Y.H.L., L.H.R., T.B.L.); Department of Cardiology, Atrial Fibrillation Study Group, Aalborg University Hospital, Aalborg, Denmark (F.S., I.E.A., T.B.L.); and University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L., D.A.L.). tobl@rn.dk.
authors.forename: Torben Bjerregaard
authors.initials: TB
authors.lastname: Larsen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D013923:Thromboembolism / Q000175:diagnosis / Q000453:epidemiology*; D013997:Time Factors
keywords: atrial fibrillation; diabetes mellitus; epidemiology; stroke; thromboembolism