Gender differences in the impact of plasma xanthine oxidoreductase activity on coronary artery spasm

Background It has been reported that decreased nitric oxide bioavailability due to increased reactive oxygen species (ROS) is one of the most important causes of coronary artery spasm (CAS). Xanthine oxidoreductase (XOR) is the rate-limiting enzyme for uric acid (UA) production and plays a pivotal role in generating ROS. It was reported that the gender differences exist in the impact of serum UA levels on cardiovascular risks. We previously demonstrated that increased plasma XOR activity is significantly associated with the incidence of CAS. However, the gender differences in the impact of plasma XOR activity on CAS remain unclear. Purpose The aim of this study was to examine the gender differences in the clinical impact of plasma XOR activity on CAS. Methods We investigated plasma XOR activity in 132 patients suspected for CAS (male, n=78; female, n=54), and underwent intracoronary acetylcholine provocation test. XOR activity assay was performed using stable isotope-labeled substrate and liquid chromatography-triple quadrupole mass spectrometry. Provoked CAS was defined as total or subtotal occlusion (≥90%) with accompanying symptoms of chest pain and/or ischemic ST-segment changes on the electrocardiogram. We excluded the patients who had significant coronary artery stenosis (≥50%) and/or were taking XOR inhibitors. Results Plasma XOR activity was significantly lower in female compared with male patients (30.3 pmol/h/mL, interquartile range (IQR) 22.8–42.7 vs. 51.7 pmol/h/mL, IQR 34.7–101.8; P Conclusions Plasma XOR activity was an independent predictor for the incidence of CAS in both genders. The impact of plasma XOR activity on CAS was stronger in female patients than in male patients. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2