title: Risk of cardiovascular diseases is increased even with mild diabetic retinopathy: the Japan Diabetes Complications Study.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is linked to cardiovascular risk in diabetic patients. This study examined whether mild-stage DR is associated with risk of coronary heart disease (CHD) and stroke in type 2 diabetic patients of the Japan Diabetes Complications Study (JDCS).
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  In the JDCS, there were 2033 Japanese persons with type 2 diabetes free of cardiovascular diseases at baseline.
  
  
  METHODS
  Diabetic retinopathy was ascertained from clinical and photographic grading (70%) following the international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Incident CHD and stroke were followed up prospectively annually up to 8 years.
  
  
  METHODS
  Eight-year incidence of CHD and stroke compared between persons with or without DR.
  
  
  RESULTS
  After adjusting for traditional cardiovascular risk factors, persons with mild to moderate nonproliferative DR had a higher risk of CHD (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.17-2.97) and stroke (HR, 2.69; 95% CI, 1.03-4.86). Presence of retinal hemorrhages or microaneurysms was associated with risk of CHD (HR, 1.63; 95% CI, 1.04-2.56) but was not associated with stroke (P = 0.06). Presence of cotton-wool spots was associated with risk of incident stroke (HR, 2.39; 95% CI, 1.35-4.24) but was not associated with CHD (P = 0.66). When information about DR was added in the prediction models for CHD and stroke based on traditional cardiovascular risk factors, the area under the receiver operating curve improved from 0.682 to 0.692 and 0.640 to 0.677, and 9% and 13% of persons were reclassified correctly for CHD and stroke, respectively.
  
  
  CONCLUSIONS
  Type 2 diabetic patients with even a mild stage of DR, such as dot hemorrhages, are already at higher risk of CHD and stroke independent of traditional risk factors.
authors.affiliation: Department of Ophthalmology, Yamagata University Faculty of Medicine, Yamagata, Japan; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Osaka Medical Center for Health Science and Promotion, Osaka, Japan. Electronic address: jdcstudy@md.tsukuba.ac.jp.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kawasaki
authors.affiliation: Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: EBM Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Ophthalmology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Ibaragi, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.affiliation: Department of Internal Medicine, Chiba University, Chiba, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.affiliation: Department of Endocrinology and Metabolism, Jichi Medical College, Shimono, Tochigi, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.affiliation: Department of Endocrinology and Diabetes, Saitama Medical University, Saitama, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Department of Biostatistics, School of Public Health, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.affiliation: The Institute for Adult Diseases, Asahi Life Foundation, Cyouh-Ku, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Akanuma
authors.affiliation: Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Tsukuba, Ibaragi, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Department of Ophthalmology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000783:Aneurysm / Q000150:complications; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology*; D048909:Diabetes Complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000150:complications* / Q000175:diagnosis; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012166:Retinal Hemorrhage / Q000150:complications; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000209:etiology
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human