The best evidence for a systemic effect of PAD comes from work showing that a single bout of exercise of the PAD legs produces a significant increase of biomarkers of oxidative stress (increased malondialdehyde, consumption of anti-oxidants) [60], increased inflammatory cells (white blood cells and neutrophils) [61, 62] and increased inflammatory cytokines (thromboxane, p-selectin, von Willebrand factor) in the blood and a significant activation of the sympathetic system of PAD patients. This evidence concerns the gene VWF and peripheral arterial disease.