Ken Watanabe 1 , Tetsuro Shishido 2 , Yoichiro Otaki 1 , Tetsu Watanabe 1 , Takayuki Sugai 1 , Taku Toshima 1 , Tetsuya Takahashi 1 , Miyuki Yokoyama 1 , Daisuke Kinoshita 1 , Takayo Murase 3 , Takashi Nakamura 4 , Masahiro Wanezaki 1 , Harutoshi Tamura 1 , Satoshi Nishiyama 1 , Hiroki Takahashi 1 , Takanori Arimoto 1 , So Yamauchi 1 , Tamon Yamanaka 1 , Takuya Miyamoto 1 , Isao Kubota 1 , Masafumi Watanabe 1
Increased reactive oxygen species (ROS) contributes to the development of endothelial dysfunction, which is involved in coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) plays a pivotal role in producing both uric acid and ROS. However, the association between plasma XOR activity and CAS has not been elucidated. The aim of this study was to investigate whether plasma XOR activity is associated with CAS. We measured XOR activity in 104 patients suspected for CAS, who presented without significant coronary artery stenosis and underwent intracoronary acetylcholine provocation tests. CAS was provoked in 44 patients and they had significantly higher XOR activity as compared with those without CAS. The patients were divided into three groups based on the XOR activity. The prevalence rate of CAS was increased with increasing XOR activity. A multivariate logistic regression analysis showed that the 3rd tertile group exhibited a higher incidence of CAS as compared with the 1st tertile group [odds ratio (OR) 6.9, P = 0.001) and the 2nd tertile group (OR 3.2, P = 0.033) after adjustment for conventional CAS risk factors, respectively. The C index was significantly improved by the addition of XOR activity to the baseline model based on CAS risk factors. Furthermore, the 3rd tertile group had the highest incidence of severe spasm defined as total obstruction, flow-limiting stenosis, diffuse spasm, multivessel spasm, and/or lethal arrhythmia. This is a first report to elucidate the association of plasma XOR activity with CAS. Increased plasma XOR activity is significantly associated with CAS.