Plasma Xanthine Oxidoreductase Activity is Associated With Edothelial Dysfunction and Increased Arterial Stiffness in a General Japanese Population: the Iwate Tohoku Medical Megabank Project

An increase in xanthine oxidoreductase (XOR) activity is related to various diseases such as diabetes, hypertension and obesity has been reported. However, so far the association with XOR activity and pathogenesis of atherosclerosis in a general Japanese population are not known. The purpose of this study is to investigate the association between XOR activity and progression of atherosclerosis including pulse wave velocity (PWV) and flow mediated dilation (FMD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 810, male / female = 271 / 539, age = 67.6 ± 7.2). Plasma levels of XOR activity in males were marginally higher than in females (89.6 ± 187.0 vs. 64.8 ± 145.8 pmol / h/ mL, p = 0.06). Arterial stiffness by PWV after log10 transformation was significantly higher in quartiles III and IV of XOR compared to quartiles I in females (F =4.768, p < 0.01) (quartiles I vs. III, 3.187 ± 0.088 vs. 3.214 ± 0.081, p < 0.01; quartiles I vs. IV, 3.187 ± 0.088 vs. 3.213 ± 0.080, p < 0.05). Endothelial function as assessed by FMD was significantly lower in quartiles III and IV compared to quartiles I in females (F = 6.074, p < 0.001) (quartiles I vs. III, 6.02 ± 3.19 vs. 4.90 ± 2.66 %, p < 0.01; quartiles I vs. IV, 6.02 ± 3.19 vs. 5.04 ± 2.76 %, p < 0.01). XOR activity was related to progression of atherosclerosis (FMD, OR = 0.930, p = 0.06) and the high risk for CVD in females (Suita Score ≥ 41, OR = 1.92, 95% confidence interval (CI) = 1.04 - 3.54, p < 0.05). XOR activity was no significant association with progression of atherosclerosis and the high risk for CVD in males. The area under the curve (AUC) for XOR activity combined with Suita score was 0.66 (95% CI = 0.52 - 0.77, p < 0.05). In conclusion, XOR activity is associated with endothelial dysfunction and increased arterial stiffness suggesting that elevated XOR activity may relate to progression of atherosclerosis and indicate the CV risk.