Risk of cardiovascular diseases is increased even with mild diabetic retinopathy: the Japan Diabetes Complications Study

Ophthalmology. 2013 Mar;120(3):574-582. doi: 10.1016/j.ophtha.2012.08.029. Epub 2012 Nov 20.


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).

Design: Prospective cohort study.

Participants: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneurysm / complications
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / etiology*
  • Diabetes Complications
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Retinopathy / complications*
  • Diabetic Retinopathy / diagnosis
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Incidence
  • Japan
  • Male
  • Middle Aged
  • Prospective Studies
  • Retinal Hemorrhage / complications
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / etiology


  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Cholesterol