Associations of plasma von Willebrand factor ristocetin cofactor activity and 5-hydroxyindole acetic acid concentrations with blood flow in lower-leg arteries in Japanese type 2 diabetic patients with normal ankle-brachial index

Abstract Aims To evaluate the associations of circulating levels of proinflammatory molecules and endothelial factors with blood flow in lower-leg arteries in diabetic patients with normal ankle-brachial index (ABI>0.9). Methods We enrolled 123 type 2 diabetic patients with normal ABI and 30 age-matched nondiabetic subjects consecutively admitted to our hospital. Flow volume and resistive index, an index of peripheral vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. An automatic device was used to measure ABI and brachial-ankle pulse-wave velocity (baPWV) for evaluation of arterial stiffness. Plasma soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) concentrations, serum high-sensitivity C-reactive protein (hsCRP) levels, plasma von Willebrand factor ristocetin cofactor activity (VWF), and plasma vasoconstrictor serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA) concentrations were measured. Results Diabetic patients had higher baPWV ( P P P P =.0224), log hsCRP ( P P P =.0015), and lower blood flow ( P P =.0019) or 5-HIAA ( P =.0011), but not sICAM-1, MCP-1, and log hsCRP, was negatively correlated with blood flow in diabetic patients. A multivariate analysis revealed that the significant independent determinants of blood flow were hypertension, use of renin–angiotensin system inhibitors, VWF and 5-HIAA ( r 2 =0.198, P Conclusions Plasma VWF and 5-HIAA concentrations are associated with blood flow and are involved in the pathogenesis of impaired peripheral circulation due to higher arterial stiffness and greater vascular resistance in lower-leg arteries in diabetic patients with normal ABI.