by Matt Batcheldor

People with microvascular disease (MVD), defined as the presence of retinopathy, nephropathy or neuropathy, were associated with a nearly four times greater likelihood of amputation compared to people without it, according to a new Vanderbilt study.

When added to peripheral artery disease, which increases the risk 14-fold, the combination markedly increased the risk to nearly 23 times more likely to need a limb removed.

The study, which was published in the August print edition of the journal Circulation, “is going to change the way we think about who is being amputated,” said lead author Joshua Beckman, MD, MSc, professor of Medicine.

The study’s other Vanderbilt authors were Meredith Duncan, MA; Quinn Wells, MD; David Wasserman, PhD; Hilary Tindle, MD; Aaron Aday, MD; and Matthew Freiberg, MD.

Microvascular disease is damage to the tiny vessels that distribute blood to tissues and organs, resulting in reduced tissue function.

Peripheral artery disease (PAD) is a narrowing of the large arteries serving the legs and feet, a manifestation of atherosclerosis or clogged arteries.

“The mechanism of adverse limb events associated with peripheral artery disease remains incompletely understood,” the study says. “We investigated whether microvascular disease is associated with amputation in a large cohort of veterans to determine whether microvascular disease diagnosed in any location increases the risk of amputation alone and in concert with peripheral artery disease.”

The study’s authors examined the Veterans Aging Cohort Study (VACS), a population of more than 125,000 military veterans with nearly 10 years of follow-up. They concluded that clinicians should routinely ask their patients with MVD and/or PAD about physical signs of lower extremity injury or lesions so they can initiate therapies to avoid amputation.

“One important take-home message of this study is that patients who have MVD in any location should examine their feet routinely and have regular foot examinations by their physicians when seen in the office,” Beckman said.

Further research is needed to understand the mechanisms by which the diseases increase the likelihood of amputation.

“Having access to large populations in the VA system provides unique resources to study these problems with extensive medical records data,” Beckman said. “These programs will allow study of genetic underpinnings and the discovery of new environmental risk factors for developing MVD and PAD.”