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      Impact of plasma xanthine oxidoreductase activity in patients with heart failure with preserved ejection fraction

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          Abstract

          Aims

          Reactive oxygen species are reportedly involved in the mechanism underlying heart failure with preserved ejection fraction (HFpEF); however, the disease pathophysiology remains poorly understood. Xanthine oxidoreductase (XOR), the rate‐limiting enzyme of purine metabolism, plays an important role in uric acid production and generates reactive oxygen species. However, the impact of plasma XOR activity on the clinical outcomes of patients with HFpEF remains unclear. The aim of this study was to investigate whether plasma XOR activity is associated with major adverse cardiovascular events (MACEs) in patients with HFpEF.

          Methods and results

          The plasma XOR activity was measured in 257 patients with HFpEF, who were then divided into three groups according to the activity levels: low XOR group (<33 pmol/h/mL, n = 45), normal XOR group (33–120 pmol/h/mL, n = 160), and high XOR group (>120 pmol/h/mL, n = 52). During the median follow‐up period of 809 days, there were 74 MACEs. Kaplan–Meier analysis revealed that the high XOR group was at the highest risk for MACEs. Multivariate analysis by Cox's proportional hazard regression approach showed that high XOR activity was significantly associated with MACEs, after adjustment for confounding factors. The patients were also divided into four groups according to the absence/presence of high XOR activity and/or hyperuricaemia. According to the multivariate Cox regression analysis, high XOR activity was associated with MACEs, regardless of the hyperuricaemia status.

          Conclusions

          Elevated plasma XOR activity is significantly associated with adverse clinical outcomes in patients with HFpEF.

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          Most cited references 25

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          Outcome of heart failure with preserved ejection fraction in a population-based study.

          The importance of heart failure with preserved ejection fraction is increasingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduced ejection fraction. From April 1, 1999, through March 31, 2001, we studied 2802 patients admitted to 103 hospitals in the province of Ontario, Canada, with a discharge diagnosis of heart failure whose ejection fraction had also been assessed. The patients were categorized in three groups: those with an ejection fraction of less than 40 percent (heart failure with reduced ejection fraction), those with an ejection fraction of 40 to 50 percent (heart failure with borderline ejection fraction), and those with an ejection fraction of more than 50 percent (heart failure with preserved ejection fraction). Two groups were studied in detail: those with an ejection fraction of less than 40 percent and those with an ejection fraction of more than 50 percent. The main outcome measures were death within one year and readmission to the hospital for heart failure. Thirty-one percent of the patients had an ejection fraction of more than 50 percent. Patients with heart failure with preserved ejection fraction were more likely to be older and female and to have a history of hypertension and atrial fibrillation. The presenting history and clinical examination findings were similar for the two groups. The unadjusted mortality rates for patients with an ejection fraction of more than 50 percent were not significantly different from those for patients with an ejection fraction of less than 40 percent at 30 days (5 percent vs. 7 percent, P=0.08) and at 1 year (22 percent vs. 26 percent, P=0.07); the adjusted one-year mortality rates were also not significantly different in the two groups (hazard ratio, 1.13; 95 percent confidence interval, 0.94 to 1.36; P=0.18). The rates of readmission for heart failure and of in-hospital complications did not differ between the two groups. Among patients presenting with new-onset heart failure, a substantial proportion had an ejection fraction of more than 50 percent. The survival of patients with heart failure with preserved ejection fraction was similar to that of patients with reduced ejection fraction. Copyright 2006 Massachusetts Medical Society.
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            Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes.

            Heart failure with preserved ejection fraction (EF) is a common syndrome, but trends in treatments and outcomes are lacking. We analyzed data from 275 hospitals in Get With the Guidelines-Heart Failure from January 2005 to October 2010. Patients were stratified by EF as reduced EF (EF <40% [HF-reduced EF]), borderline EF (40%≤EF<50% [HF-borderline EF]), or preserved (EF ≥50% [HF-preserved EF]). Using multivariable models, we examined trends in therapies and outcomes. Among 110 621 patients, 50% (55 083) had HF-reduced EF, 14% (15 184) had HF-borderline EF, and 36% (40 354) had HF-preserved EF. From 2005 to 2010, the proportion of hospitalizations for HF-preserved EF increased from 33% to 39% (P<0.0001). In multivariable analyses, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers at discharge decreased in all EF groups, and β-blocker use increased. Patients with HF-preserved EF less frequently achieved blood pressure control (adjusted odds ratio, 0.44 versus HF-reduced EF; P<0.001) and were more likely discharged to skilled nursing (adjusted odds ratio, 1.16 versus HF-reduced EF; P<0.001). In-hospital mortality for HF-preserved EF decreased from 3.32% in 2005 to 2.35% in 2010 (adjusted odds ratio, 0.89 per year; P=0.01) but was stable for patients with HF-reduced EF (3.03%-2.83%; adjusted odds ratio, 0.93 per year; P=0.10). Hospitalization for HF-preserved EF is increasing relative to HF-reduced EF. Although in-hospital mortality for patients with HF-preserved EF declined over the study period, an important opportunity remains for identifying evidence-based therapies in patients with HF-preserved EF.
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              Heart Failure with Preserved Ejection Fraction.

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                Author and article information

                Contributors
                tewatana@med.id.yamagata-u.ac.jp
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                20 May 2020
                August 2020
                : 7
                : 4 ( doiID: 10.1002/ehf2.v7.4 )
                : 1735-1743
                Affiliations
                [ 1 ] Department of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine 2‐2‐2 Iida‐Nishi Yamagata 990‐9585 Japan
                [ 2 ] Mie Research Laboratories Sanwa Kagaku Kenkyusho Co., Ltd. Mie Japan
                Author notes
                [* ] Correspondence to: Tetsu Watanabe, Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2‐2‐2 Iida‐Nishi, Yamagata 990‐9585, Japan. Tel: +81‐23‐628‐5302; Fax: +81‐23‐628‐5305. Email: tewatana@ 123456med.id.yamagata-u.ac.jp

                Article
                EHF212734 ESCHF-20-00079
                10.1002/ehf2.12734
                7373896
                32432414
                © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                Page count
                Figures: 3, Tables: 4, Pages: 9, Words: 3242
                Product
                Funding
                Funded by: Sanwa Kagaku Kenkyusho Co., Ltd.
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                August 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:22.07.2020

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