The association between serum urate levels and arterial stiffness/endothelial function in stroke survivors

There is increasing evidence that serum uric acid is an independent marker of cardiovascular risk. We have shown previously that high urate is associated with cardiac death in stroke survivors independently of conventional risk factors. We sought to determine in stroke survivors the association between high urate levels and arterial stiffness and endothelial function. One hundred and twenty stroke survivors were recruited. We assessed pulse wave velocity of the carotid artery using an echotracking ultrasound system. Endothelial function was assessed by measuring forearm skin blood flow responses, using laser Doppler imaging, to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Patients with high serum urate (0.42-0.71 mmol/l) had a greater pulse wave velocity (P<0.02) and a lower ACh response (P=0.001) than patients with lower urate (0.12-0.28 mmol/l). Pulse wave velocity significantly correlated with serum urate (r=-0.358, P<0.001), HDL cholesterol (r=-0.22, P=0.02), and male gender (r=0.26, P=0.005). The ACh response significantly correlated with serum urate (r=-0.30, P=0.001), male gender (r=-0.45, P<0.001), HDL cholesterol (r=0.42, P<0.001), and triglycerides (r=-0.24, P=0.01). Stepwise multiple regression showed that serum urate was significantly associated with pulse wave velocity (beta=0.35, P<0.001), independently of other risk variables. For the ACh response the significant determinants were male gender (beta=-0.38, P<0.001) and HDL cholesterol (beta=0.23, P=0.018). We have shown for the first time that elevated serum urate is associated with increased arterial stiffness in stroke survivors, independently of other risk factors. A therapeutic intervention trial of lowering of serum urate is required to see whether this will impact positively on mortality and morbidity in patients with high-risk of strokes.