title: Cardiovascular disease in patients with osteogenesis imperfecta - a nationwide, register-based cohort study.
abstract: BACKGROUND
  Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI.
  
  
  OBJECTIVE
  To investigate the risk of symptomatic CVD in OI.
  
  
  METHODS
  A Danish nationwide, population-based and register-based longitudinal open cohort study.
  
  
  METHODS
  All patients registered with the diagnosis of OI from 1977 to 2013 and a reference population matched 5:1 to the OI cohort.
  
  
  METHODS
  Sub-hazard ratios for mitral and aortic valve regurgitation, atrial fibrillation and flutter, heart failure and vascular aneurisms and dissections comparing the OI cohort to the reference population.
  
  
  RESULTS
  We identified 687 cases with OI (379 women) and included 3435 reference persons (1895 women). The SHR was 6.3 [95% CI: 2.5-15.5] for mitral valve regurgitation, 4.5 [95% CI: 1.4-13.9] for aortic valve regurgitation, 1.7 [95% CI: 1.1-2.8] for atrial fibrillation/flutter, and 2.3 [95% CI: 1.4-3.7] for heart failure. The SHRs were not increased arterial aneurisms or dissections.
  
  
  CONCLUSIONS
  Our results were limited by lacking clinical information about phenotype and genotype of the included patients.
  
  
  CONCLUSIONS
  We confirm that patients with OI have an increased risk of CVD compared to the general population. This held true even when adjusting for factors that are known to contribute to development of these diseases. Our results suggest that the collagenopathy seen in OI may be part of the pathogenesis of CVD in OI.
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Endocrinology, Hospital of Southwest Denmark, Esbjerg, Denmark. Electronic address: Lfolkestad@health.sdu.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Folkestad
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: jannie.hald@midt.rm.dk.
authors.forename: Jannie Dahl
authors.initials: JD
authors.lastname: Hald
authors.affiliation: Department of Endocrinology, Hospital of Southwest Denmark, Esbjerg, Denmark. Electronic address: jeppe.gram@rsyd.dk.
authors.forename: Jeppe
authors.initials: J
authors.lastname: Gram
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: bente.langdahl@aarhus.rm.dk.
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.affiliation: Department of Endocrinology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: pernille.hermann@rsyd.dk.
authors.forename: Anne Pernille
authors.initials: AP
authors.lastname: Hermann
authors.affiliation: Department of Cardiology, Odense University Hospital, Denmark. Electronic address: Axel.Diederichsen@rsyd.dk.
authors.forename: Axel Cp
authors.initials: AC
authors.lastname: Diederichsen
authors.affiliation: Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Medicine, Holbæk Hospital, Holbæk, Denmark; Odense Exploratory Patient Network (OPEN), Odense University Hospital, Denmark. Electronic address: b.abrahamsen@physician.dk.
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.affiliation: Department of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: kim.brixen@rsyd.dk.
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000175:diagnosis* / Q000453:epidemiology*; D011897:Random Allocation; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
keywords: Connective tissue disorders; Epidemiology; Osteogenesis imperfecta; Register based nationwide; Risk of cardiovascular disease