Medscape: Retinopathy Signals Future PAD, Critical Limb Ischemia Risk

Having retinopathy predicted an increased risk of developing peripheral artery disease (PAD), especially the severe form of the disease, critical limb ischemia, in a new study[1].

Specifically, participants in the Atherosclerosis Risk in Communities (ARIC) study who had retinopathy had a 2.26-fold higher risk of developing PAD and a 3.41-fold higher risk of developing critical limb ischemia than their peers without retinopathy during an almost 20-year follow-up, after adjustment for known risk factors, including diabetes.

Chao Yang (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD) presented these findings in a poster at the EPI|LIFESTYLE 2017 Scientific Sessions.

The study is novel, “because PAD is generally considered a large-artery disease, and we found an association with microvascular disease,” Yang told heartwire from Medscape.

It suggests that when patients with type 2 diabetes have retinal photographs taken to detect diabetic retinopathy, as recommended by American Diabetes Association’s 2016 Standards of Medical Care guidelines, finding retinopathy could potentially identify patients at higher risk of future PAD and critical limb ischemia.

“These findings provide novel evidence of a direct and strong association between objective signs of microvascular disease in the retina and the development and severity of peripheral macrovascular disease in the limbs,” Dr Dana Dabelea (University of Colorado, Aurora), who was not involved in the study, agreed in an email comment to heartwire .

The retinal lesions associated with future PAD had characteristics seen in nonproliferative diabetic retinopathy (microaneurysms, hemorrhages, and exudates), rather than features seen in hypertensive retinopathy (such as arteriovenous nicking and focal narrowing), which makes sense, since the association between retinopathy and future PAD was stronger in patients with diabetes, Dabelea noted.

The study reinforces that regular eye exams are important, and “identification of such [retinal] abnormalities should trigger more aggressive risk-factor control (glucose, lipids, blood pressure, smoking cessation, etc) to prevent the progression of retinopathy, but also [to prevent] the development and progression of macrovascular disease, including PAD,” she summarized.

Microvascular Eye Disease, Future Narrowed Leg Arteries 

Whether retinal disease might predict future narrowed leg arteries has not been systematically evaluated in a large cohort study, Yang and colleagues write.

To investigate this, they analyzed data from 9371 participants in ARIC who did not have PAD and were 49 to 73 years old at the third visit  (in 1993 to 1995) when they had retinal photography exams.

During a mean follow-up of 19 years, 304 participants developed PAD, defined as hospitalization with a diagnosis of PAD or leg revascularization.

Of these, 92 patients had severe PAD or critical limb injury, defined as leg ulcer, gangrene, or amputation.

The patients who developed PAD were more likely to be male (60% vs 44%) and have a poorer cardiovascular risk profile at baseline.

Compared with other patients, the patients who developed PAD were older (mean age 61 vs 59) with a higher mean systolic blood pressure (130 vs 123 mm Hg), and they were more likely to be taking a cholesterol-lowering medication (17% vs 9%) or have diabetes (39% vs 13%) or coronary heart disease (24% vs 6%; all P<0.001).

At baseline, 7.2 % of the patients had retinopathy—defined as blot- or flame-shaped retinal hemorrhages, hard or soft exudates, microaneurysms, or other features.

Each of these retinal features was more strongly associated with critical limb injury than with PAD (hazard ratio [HR] range 3.1 to 6.5 for critical limb injury; HR range 2.2 to 3.3 for PAD; all P<0.05, except for soft exudates)—after adjustment for demographic variables, cardiovascular risk factors, and cardiovascular disease.

The microvascular wall diameter findings (arteriovenous nicking, central retinal arteriolar equivalent [CRAE], and focal narrowing), however, were not associated with an increased risk of PAD or critical limb ischemia, after adjustment for the same confounders.

In subgroup analysis, the association between retinopathy and PAD or critical limb ischemia was strongest among patients with diabetes.

“Our results suggest the importance of microvascular wall fragility/permeability in the development of PAD,” Yang and colleagues conclude.

“Further research should focus on identifying common mechanisms [for developing retinopathy and PAD] and explore preventive approaches that may benefit both the eyes and the limbs of affected individuals,” Dabelea said.

In the meantime, the study suggests, clinicians should pay close attention to retinal exam findings that suggest that a patient is at increased risk of PAD or critical limb injury.

Click here to see the original article on the Medscape website.