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Retinopathy and other microvascular diseases are linked to a substantial risk of adverse limb events in peripheral artery disease (PAD), a study found.

The incidence of amputation was 0.23 per 1,000 person-years among people who had neither microvascular disease nor PAD in the Veterans Aging Cohort Study. Those who had one or both showed increased risk:

• Microvascular disease: 1.59 amputations per 1,000 person-years (adjusted HR 3.74, 95% CI 3.03-4.62)
• PAD: 4.54 amputations per 1,000 person-years (aHR 13.86, 95% CI 11.25-17.07)
• Microvascular disease plus PAD: 13.22 amputations per 1,000 person-years (aHR 22.71, 95% CI 18.34-28.12)

"One take-home message from this work is that MVD [microvascular disease] alone is associated with 18% of all amputations and 15% of all below-knee amputations implicating MVD as an important risk for amputation," noted the group led by Joshua Beckman, MD, of Vanderbilt University Medical Center in Nashville, Tennessee. Their study was published online in .

More than 40% of all amputations occurred among people with both PAD and microvascular disease, though they represented just 4% of the population.

"MVD likely participates importantly in the development of adverse limb events in PAD and suggests additional patient populations who may benefit from greater foot surveillance to minimize amputation," the authors concluded.

They cited prior research showing a stronger link between severity of large vessel disease in the lower extremities and cardiovascular events than seen with limb complications.

"These observations suggest the existence of other important contributors to the development of limb symptoms beyond large artery atherosclerosis," they wrote.

Microvascular disease -- retinopathy, neuropathy, and nephropathy -- tended to be associated with below-ankle amputations, whereas PAD was tied to below- and above-knee amputations.

"I think the findings are important in that loss of a limb due to vascular diseases is considered an 'irreversible harm' event meaning that even a minor amputation involving the toes or foot can alter the patient's function and quality of life," commented William Hiatt, MD, of University of Colorado School of Medicine, Denver.

"What is new in this article is evaluating the combination of both large vessel PAD and microvascular disease in defining that risk," he told 番茄社区app. "I suspect part of the risk enhancement of microvascular disease is due to the associated foot infections and poor wound healing."

The Veterans Aging Cohort Study was a prospective longitudinal study originally intended to follow people with and without HIV.

After excluding people who went from HIV-negative to HIV-positive during follow-up and those with known prior lower limb amputations, Beckman and colleagues ended up with more than 125,000 participants for their analysis.

Altogether, amputation occurred at a rate of 1.16 per 1,000 person-years over 9.3 years of follow-up.

At the time of amputation, most people had some form of microvascular disease: retinopathy (69%), nephropathy (67%), or neuropathy (78%).

People with PAD or microvascular disease were more likely to have hypertension, diabetes, anemia, and chronic obstructive pulmonary disease.

The observational results could have been subject to other residual confounding despite efforts at adjustment and relied on diagnostic codes to identify patients with PAD or microvascular disease, the researchers acknowledged.

"One important question in these findings is the role of diabetes," Beckman's team added. "Our data demonstrate a similar increase in associated risk of amputation in the presence or absence of diabetes. Diabetes is an important contributor to the microvascular disease and PAD population burden and provides multiple mechanisms by which amputation may develop."

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