Microvascular disease, a disorder of very small blood vessels, may increase the risk of leg amputation independent of other blood vessel conditions and regardless of the location of the microvascular issue, such as eyes (retinopathy), kidneys (nephropathy) or feet (neuropathy). Study participants with both microvascular disease and peripheral arterial disease (PAD) had an almost 23-fold increased risk of amputation compared to those without any vascular disease.