Association of plasma xanthine oxidoreductase activity with severity and clinical outcome in patients with chronic heart failure

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• 作者：Yoichiro Otaki^a ; Tetsu Watanabe^a ; ^{tewatana@med.id.yamagata-u.ac.jp} ; Daisuke Kinoshita^a ; Miyuki Yokoyama^a ; Tetsuya Takahashi^a ; Taku Toshima^a ; Takayuki Sugai^a ; Takayo Murase^b ; Takashi Nakamura^c ; Satoshi Nishiyama^a ; Hiroki Takahashi^a ; Takanori Arimoto^a ; Tetsuro Shishido^a ; Takuya Miyamoto^a ; Isao Kubota^a
• 关键词：Xanthine oxidoreductase ; Uric acid ; Heart failure ; Cardiac prognosis
• 刊名：International Journal of Cardiology
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：228
• 期：Complete
• 页码：151-157
• 全文大小：789 K
• 卷排序：228

文摘

Oxidative stress due to purine degradation is associated with the development of chronic heart failure (CHF). Xanthine oxidoreductase (XOR) is a rate-limiting enzyme of purine degradation that plays a key role in uric acid (UA) production with a resultant increase in reactive oxygen species. However, the relationship between plasma XOR activity and CHF severity and clinical outcome remains unclear.Methods and resultsWe measured XOR activity in 440 patients with CHF and 44 control subjects. Abnormally high and low XOR activities were identified based on the results for 95% of the control subjects (high and low XOR activities ≥ 120 and < 33 pmol/100 μL/h, respectively). The prevalence rates of high and low XOR activities increased with advancing New York Heart Association functional class. There were 158 cardiac events during a median follow-up period of 1034 days. Multivariate Cox proportional hazard regression analysis showed that both high and low XOR activities were significantly associated with cardiac events in patients with CHF after adjustment for confounding risk factors including serum UA and loop diuretic use. Kaplan–Meier analysis revealed that the cardiac event rate was significantly higher in patients with either high or low XOR activity. The net reclassification index was significantly improved by adding XOR activity to the basic risk factors.ConclusionsWe provide the first evidence of an association of plasma XOR activity with CHF severity and clinical outcome. Plasma XOR activity could be used to identify high-risk CHF patients and could be a therapeutic target for XOR inhibitors.