title: Diabetic retinopathy is associated with mortality and cardiovascular disease incidence: the EURODIAB prospective complications study.
abstract: OBJECTIVE
  To study the relationship of nonproliferative and proliferative retinopathy with all-cause mortality and cardiovascular disease (CVD) incidence in type 1 diabetic patients and, additionally, the role of cardiovascular risk factors in these associations.
  
  
  METHODS
  This prospective study included 2,237 type 1 diabetic patients from 31 centers in 16 European countries at baseline, aged 15-60 years, who were examined for retinopathy by taking two-field 45 degrees fundus photographs, which were centrally graded. Mortality and cardiovascular morbidity follow-up was assessed 6-8 years after baseline examination according to a standardized protocol.
  
  
  RESULTS
  After 7.9 years of follow-up, 64 patients had died and 128 patients had incident CVD. The age- and sex-adjusted hazard ratios (HRs) of all-cause mortality were 1.45 (95% CI 0.71-2.96) and 4.16 (1.96-8.84) in patients with nonproliferative and proliferative retinopathy at baseline, respectively. Adjustments for cardiovascular risk factors completely obliterated the association with nonproliferative retinopathy, whereas the association with proliferative retinopathy remained twofold increased, although nonsignificant. The age- and sex-adjusted HRs of incident CVD were 1.73 (1.15-2.60) and 2.05 (1.22-3.45) in patients with nonproliferative and proliferative retinopathy, respectively. After adjustments for cardiovascular risk factors, both associations were attenuated and lost statistical significance.
  
  
  CONCLUSIONS
  This study shows that type 1 diabetic patients with nonproliferative or proliferative retinopathy have an increased risk for all-cause mortality and incident CVD. The presence of cardiovascular risk factors explained the associations to a large extent, except for the associations with proliferative retinopathy, which suggests that other shared mechanisms may be involved.
authors.affiliation: Department of Ophthalmology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, Netherlands. m.vanhecke@vumc.nl
authors.forename: Manon V
authors.initials: MV
authors.lastname: van Hecke
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Bettine C P
authors.initials: BC
authors.lastname: Polak
authors.forename: John H
authors.initials: JH
authors.lastname: Fuller
authors.forename: Anne Katrin
authors.initials: AK
authors.lastname: Sjolie
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kofinis
authors.forename: Raoul
authors.initials: R
authors.lastname: Rottiers
authors.forename: Massimo
authors.initials: M
authors.lastname: Porta
authors.forename: Nish
authors.initials: N
authors.lastname: Chaturvedi
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003922:Diabetes Mellitus, Type 1 / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000453:epidemiology*; D003930:Diabetic Retinopathy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013997:Time Factors