Xanthine Oxidoreductase Plays a Key Role in Cardio-Hepatic Vicious Cycle in Patients With Heart Failure

Background: Cardio-hepatic interaction forms a vicious cycle which worsens each other, finally leading to poor clinical outcome in patients with chronic heart failure (CHF). Xanthine oxidoreductase (XOR), which is a rate-limiting enzyme of purine degradation abundantly expressed in the liver, is reported to be associated with cardiac events in patients with CHF. We hypothesized that XOR activity is associated with liver dysfunction and plays a key role in the development of cardio-hepatic interaction in patients with CHF. Methods and Results: We enrolled consecutive 440 CHF patients and measured XOR activity and liver enzymes. There were 158 cardiac events during the median follow-up period of 1034 days. XOR activity was significantly related to levels of aspartate aminotransferase and alanine aminotransferase (r = 0.551, P6lt; 0.0001 and r = 0.612, P < .0001, respectively). Multivariate logistic analysis demonstrated that alanine aminotransferase level was related to high XOR activity. All patients were divided into four groups based on the XOR activity and liver dysfunction. Multivariate Cox proportional hazard analysis demonstrated that comorbid of high XOR activity and liver dysfunction was associated with cardiovascular events. Kaplan-Mayer analysis showed that patients with high XOR activity and liver dysfunction had the greatest risk in patients with CHF. Conclusion: XOR activity was significantly associated with liver dysfunction. The comorbid condition was related to cardiac events, suggesting the importance of XOR activity in cardio-hepatic interaction.