Although atherosclerosis and retinopathy are generally considered unrelated conditions, increasing evidence suggests that there may be shared risk factors and/or mechanisms contributing to both complications, according to Peter D. Reaven, MD.1

“Few studies have been able to directly compare the extent of atherosclerosis with categories of retinopathy,” he said during a presentation at the American Diabetes Association’s 67th Scientific Sessions in Chicago. Dr. Reaven is Associate Professor of Clinical Medicine at the University of Arizona College of Medicine and Director, Diabetes Program at the Carl T. Hayden VA Medical Center in Phoenix.

To compare the extent of atherosclerosis with categories of retinopathy, Dr. Reaven and colleagues assessed the cross-sectional association between retinopathy and atherosclerosis as measured by computed tomography (CT)-detectable coronary artery calcium (CAC) in a subgroup of patients with type 2 diabetes. The patients were enrolled in the Veterans Affairs Diabetes Trial (VADT) (see VADT at a Glance). Retinopathy was assessed by seven-field stereo fundus photography, and the photos were centrally read at the University of Wisconsin.

A total of 211 patients (95% of whom were male), with a mean age of 62.1 ±9.2 years, a mean type 2 diabetes duration of 12.5 ±8.5 years, and A1C levels 9.2 ±1.4% were included.

The investigators found that retinopathy correlated with CAC—both by absolute score (r=0.18, P=.008) and by categories of retinopathy. “The median CAC, measured by Agatston score, increased across retinopathy categories,” Dr. Reaven said (see CAC and Agatston Score).

Among patients with no retinopathy, the median CAC score was 197; for patients with microaneurisms only, it was 262; for those with mild nonproliferative diabetic retinopathy (NPDR), 364; for moderate-to-severe NPDR, 300; and for patients with proliferative retinopathy (PDR), 981.

According to the abstract, investigators performed a multivariable linear regression analysis with forward and backward elimination to find a parsimonious subset of risk factors to include with PDR in predicting CAC. Dr. Reaven and his colleagues found that after adjustment for age, HDL cholesterol, insulin use, prior cardiovascular event, prior coronary revascularization, and ethnicity-race, PDR was significantly (P=.04) associated with the log10 of CAC+1. This indicated a 3.2-fold increase in CAC if PDR was present.

Although hypertension history, baseline blood pressure, A1C, diabetes duration were also candidate variables in the multivariable modeling, they were not significant, the investigators found. “Moreover, using logistic regression, individuals with PDR were approximately sixfold more likely to have CAC >400—a clinically relevant high-risk group—compared with those with no PDR,” Dr. Reaven said. “This was even after adjustment for other cardiovascular disease [CVD] risk factors.”

These data indicate a “surprisingly strong” relationship between retinopathy and the extent of coronary atherosclerosis as indicated by CAC, he added. “The data suggest (1) that identifying type 2 diabetes patients with PDR may predict those who are at uniquely high risk for clinical CVD, and (2) the potential to identify and treat shared risk factors for these common micro- and macrovascular complications.”

Peter D. Reaven, MD, is Associate Professor of Clinical Medicine at the University of Arizona College of Medicine; Research Professor of Cellular and Molecular Biology at Arizona State University; and Director, Diabetes Program at the Carl T. Hayden VA Medical Center in Phoenix. He may be reached at Peter.Reaven@va.gov.

1. Reaven PD, Moritz T, Emanuele N, et al. Proliferative diabetic retinopathy is strongly related to coronary artery calcium in the Veterans Affairs Diabetes Trial (VADT). #0268. Presented at the American Diabetes Association’s 67th Scientific Sessions. June 22-26, 2007. Chicago.