Highlights
- •Heart failure with atrial fibrillation (HF-AF) had higher plasma xanthine oxidoreductase (XOR) activity than HF with sinus rhythm (HF-SR).
- •Persistent AF was independently associated with increased XOR activity.
- •High plasma XOR activity was an independent risk factor for major adverse cardiovascular events in HF-AF.
- •The prediction model was improved by the addition of plasma XOR activity.
Abstract
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 04, 2023
Accepted:
February 7,
2023
Received in revised form:
February 2,
2023
Received:
November 20,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
