Diabetic Retinopathy, its Progression and Incident Cardiovascular Events in the ACCORD Trial

  1. for the ACCORD Study Group
  1. 1Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
  2. 2Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
  3. 3Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
  4. 4Case Western Reserve University and Cleveland VA Medical Center, Cleveland, Ohio
  5. 5Memphis Veterans Affairs Medical Center, Memphis, Tennessee
  6. 6Metrohealth System and Case Western Reserve University School of Medicine, Cleveland, Ohio
  7. 7SUNY Downstate Medical Center and Kings Country Hospital Center, Brooklyn, New York
  8. 8North Bronx Healthcare Network and Albert Einstein College of Medicine, Bronx, New York
  9. 9National Eye Institute, National Institutes of Health, Bethesda, Maryland
  1. Corresponding author: Hertzel C. Gerstein, gerstein{at}


OBJECTIVE Both the presence of diabetic retinopathy and its severity are significantly associated with future cardiovascular (CV) events. Whether its progression is also linked to incident CV outcomes hasn’t been assessed.

RESEARCH DESIGN AND METHODS The relationship between retinopathy, its 4-year progression, and CV outcomes (CV death or nonfatal myocardial infarction or stroke) was analyzed in participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who also participated in the ACCORD Eye Study. Retinopathy was classified as either none, mild, moderate, or severe, and worsening was classified as a <2-step, 2–3-step, or >3-step change (that included incident laser therapy or vitrectomy).

RESULTS Participants (n = 3,433) of mean age 61 years had baseline retinal photographs (seven stereoscopic fields). Compared with no retinopathy, the adjusted HRs (95% CI) for the CV outcome rose from 1.49 (1.12–1.97) for mild retinopathy to 2.35 (1.47–3.76) for severe retinopathy. A subset of 2,856 was evaluated for progression of diabetic retinopathy at 4 years. The hazard of the primary outcome increased by 38% (1.38 [1.10–1.74]) for every category of change in retinopathy severity. Additional adjustment for the baseline and follow-up levels of A1C, systolic blood pressure, and lipids either individually or together rendered the relationships between worsening and CV outcomes nonsignificant.

CONCLUSIONS Both the severity of retinopathy and its progression are determinants of incident CV outcomes. The retina may provide an anatomical index of the effect of metabolic and hemodynamic factors on future CV outcomes.

  • Received July 3, 2012.
  • Accepted October 21, 2012.

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