LOS ANGELES — Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.

In a new study with nearly 3000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.

Ka-Ho Wong, BS, MBA

"We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease," lead author Ka-Ho Wong, BS, MBA, told Medscape Medical News.

However, "we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease," he said. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.

The study findings were released February 12 in advance of formal presentation at next week's International Stroke Conference (ISC) 2020 in Los Angeles.

Common Predictor of Vascular Disease

Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.

This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.

To find out more, Wong and colleagues analyzed 2828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy with another 1954 diabetics without this complication. The average age was 62 years and 62% were men.

Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.

A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.

The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) vs 31% of those without a stroke (P = .016).

The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10 - 2.32; P = .015).

Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).

The study was a secondary analysis, so information on stroke type and location were unavailable.

The Big Picture

"Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications," the researchers note.

Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.

"It's important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association," said Wong.

"Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association]," he added.

Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, "which would have important implications for prevention efforts," he said.

Consistent Findings

"The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn't surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship," Larry B. Goldstein, MD, said in a video commentary on the findings.

"The results are actually quite consistent with several other studies that have evaluated the same relationship," added Goldstein, who is chair of the Department of Neurology and co-director of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, in Lexington.

Wong and Goldstein have disclosed no relevant financial relationships. The NIH's National Institute of Neurological Disorders and Stroke funded the study.

International Stroke Conference (ISC) 2020: Oral Presentation 154. Presented February 21, 2020.

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