Background: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme for uric acid (UA) production and plays an important role in generating reactive oxygen species (ROS). Overproduction of ROS is reported to contribute to the pathophysiology of atrial fibrillation (AF), however, the prognostic impact of plasma XOR activity in patients with heart failure (HF) with AF is undetermined.
Methods: We measured plasma XOR activity in 475 HF patients, including those with sinus rhythm (HF-SR, n = 211), and those with AF (HF-AF, n = 264). The type of AF included paroxysmal (n = 128) and persistent (n = 136) AF. All patients were prospectively followed up for a median period of 804 days.
Results: HF-AF patients had significantly higher plasma XOR activity and serum UA levels compared with HF-SR patients. Both plasma XOR activity and serum UA levels were higher in patients with persistent AF than in those with SR and with paroxysmal AF. Multivariate linear regression analysis showed that persistent AF was independently associated with increased XOR activity. During the follow-up period, there were 79 major adverse cardiovascular events (MACEs). HF-AF patients with MACEs had higher plasma XOR activity compared with those without MACEs, while there were no significant differences in serum UA levels. Multivariate Cox proportional analysis showed that high XOR activity was an independent risk factor for MACEs after adjustment for confounding factors. Kaplan-Meier analysis revealed that the high XOR activity group had a higher risk of MACEs than the low XOR activity group. The prediction model was significantly improved by the addition of XOR activity to the basic predictors.
Conclusions: HF-AF patients had significantly higher plasma XOR activity compared with HF-SR patients. Plasma XOR activity proved to be a reliable indicator for MACEs in HF-AF patients.
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