Elevated albumin excretion rate (AER) independently predicts total and cardiovascular mortality in a variety of conditions, although the exact mechanisms are unknown. Laser Doppler fluximetry was used to study associations with risk factors and renal damage (AER calculated from a timed overnight urine collection) in 188 people without diabetes and 117 individuals with diabetes. Skin flow (flux) in response to arterial occlusion (ischemia) was measured. Three distinct patterns of postischemic peak flow were observed: 1) gradual rise to peak (normal), 2) nondominant early peak, and 3) dominant early peak. Those with a dominant early peak were more likely to have diabetes (P = 0.01), hypertension (P = 0.001), and obesity (P < 0.001) and had a higher AER (12.6 microg/min [95% CI 7.8-20.2] vs. 7.2 [5.5-9.5] nondominant early peak group and 3.7 [3.2-4.1] normal group; P < 0.001 for trend). This could not be accounted for by conventional cardiovascular risk factors (P < 0.001 after adjustment). A rapid peak flow response after ischemia is associated with an elevated AER and increased cardiovascular risk. This may represent shared mechanistic pathways and causative or con-sequential changes in the microvasculature and supports the hypothesis that microvascular dysfunction may contribute to large vessel pathophysiology.