The Effect of Xanthine Oxidase Inhibition Upon Ejection Fraction in Heart Failure Patients: La Plata Study

Cingolani, Horacio E.; Plastino, Juan Angel; Escudero, Eduardo Manuel; Mangal, Brian; Brown, Joanne; Pérez, Néstor Gustavo

doi:10.1016/j.cardfail.2006.05.005

Cited by 104 publications

(92 citation statements)

References 33 publications

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“…The mechanism underlying these associations remains uncertain; however, elevation of SUA may reflect increased xanthine oxidase activity leading to enhanced oxidative stress, which may play a role in the development of cardiac remodeling and dysfunction (16). Several studies have previously examined whether SUA-lowering therapy leads to clinical and functional improvement of heart failure; however, the results are not consistent (6,14,20,30).…”

Section: Discussionmentioning

confidence: 78%

Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction

Nogi

Fujita

Okamoto

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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N. Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction. Am J Physiol Heart Circ Physiol 309: H986 -H994, 2015. First published July 25, 2015 doi:10.1152/ajpheart.00402.2015.-Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, Ն6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P Ͻ 0.05) and 8.06 (P Ͻ 0.001), respectively, when compared with the first SUA quartile (Յ4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (Ն5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P Ͻ 0.05) when compared with the first SUA quartile (Յ4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men. ALONGSIDE THE AGING POPULATION, the prevalence of heart failure with preserved ejection fraction, or diastolic heart failure, is increasing, and this increase is more prominent in women than in men, who demonstrate striking disparity with regard to heart failure with reduced ejection fraction (2,3,25). This disparity might be explained by the fact that aging-associated concentric ventricular remodeling is greater in the female heart (35). In addition to sex difference, several clinical characteristics are known to be associated with heart failure with preserved ejection fraction including older age, hypertension, obesity, diabetes, and potassium concentration (23). The prognosis for diastolic heart failure may be as poor as that for systolic heart failure (11, 31), and most therapies that have been shown to be effective for systolic heart failure seem to be least effective for diastolic heart failure (11,15,26,32,42). Thus factors that are not only related to diastolic dysfunction risk but also potentially modifiable by lifestyle interventions or certain medication need to be identified for the better management of diastolic cardiac dysfunction, especially in wom...

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Section: Discussionmentioning

confidence: 78%

Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction

Nogi

Fujita

Okamoto

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…9 Gavin and Struthers 8 have shown that UA lowering with the XO inhibitor allopurinol resulted in reduced BNP levels in patients with systolic CHF. Cingolani et al 18 reported improved LVEF after therapy with oxypurinol, the active metabolite of allopurinol. From the OPT-CHF [Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure] trial, it has recently been reported that treatment with oxypurinol did not produce clinical improvements in unselected patients with CHF.…”

Section: Discussionmentioning

confidence: 99%

Uric Acid-Lowering Treatment With Benzbromarone in Patients With Heart Failure

Oginö

Kato

Furuse

et al. 2010

Circ: Heart Failure

173

110

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Background-Hyperuricemia is common in chronic heart failure (CHF), and it is a strong independent marker of prognosis. Upregulated xanthine oxidase (XO) activity and impaired renal excretion have been shown to account for increased serum uric acid (UA) levels in CHF. Therapeutic interventions with allopurinol to reduce UA levels by XO inhibition have been shown to be beneficial. Discussions are ongoing whether UA itself is actively involved or it is a mere marker of upregulated XO activity within CHF pathophysiology. Therefore, the aim of this study was to test the effect of lowering UA by uricosuric treatment without XO inhibition on hemodynamic and metabolic characteristics of CHF. Impaired renal excretion of UA was taken into account. Methods and Results-Serum UA (SUA), urinary UA (uUA) excretion, and renal clearance test for UA (Cl UA ) were measured in 82 patients with CHF. SUA was significantly increased compared with controls of similar age (control, 5.45Ϯ0.70 mg/dL; New York Heart Association I, 6.48Ϯ1.70 mg/dL; New York Heart Association II, 7.34Ϯ1.94 mg/dL; New York Heart Association III, 7.61Ϯ2.11 mg/dL; PϽ0.01). Patients with CHF showed lower uUA excretion and Cl UA . On multivariate analysis, insulin, brain natriuretic peptide (PϽ0.01), and creatinine levels (Pϭ0.05) showed independent correlation with SUA. The treatment effect of the uricosuric agent benzbromarone was tested in 14 patients with CHF with hyperuricemia in a double-blind, placebo-controlled, randomized crossover study design. Benzbromarone significantly decreased SUA (PϽ0.01). Brain natriuretic peptide, left ventricular ejection fraction, and dimensions in echocardiographic assessment did not change after benzbromarone therapy. In contrast, fasting insulin (placebo, 18.8Ϯ8.9 U/mL; benzbromarone, 11.0Ϯ6.2 U/mL; PϽ0.05), homeostasis model assessment of insulin resistance index (placebo, 5.4Ϯ2.6; benzbromarone, 3.0Ϯ1.7; PϽ0.05), and tumor necrosis factor-␣ (placebo, 2.59Ϯ0.63 pg/mL; benzbromarone, 2.14Ϯ0.51 pg/mL; PϽ0.05) improved after benzbromarone, and the changes in tumor necrosis factor-␣ levels were correlated with reduction of SUA (PϽ0.05). Conclusions-These results show that UA lowering without XO inhibition may not have an effect on hemodynamic impairment in CHF pathophysiology. To the extent that these data are correct, this finding suggests that upregulated XO activity rather than UA itself is actively involved in hemodynamic impairment in CHF. Clinical Trial Registration-clinical trials.gov. Identifier: NCT00422318.(Circ Heart Fail. 2010;3:73-81.)

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“…Not only transporters, but also transcriptional factors, signaling receptors, enzymes are involved in serum UA level. Table 1 shows association between life-style related diseases and UA metabolism [16][17][18][19][20][21][22][23][24] . Distinguishing cause and effect is difficult; some diseases raise SUA level, but UA affect disease onset or progression.…”

Section: Factors That Define Serum Uric Acid Levelsmentioning

confidence: 99%

“…These studies show that UA is an in- (especially exercise time until ST depression) when a high dose of 600 mg/d of allopurinol was administered to patients with chronic stable angina [76] . Allopurinol treatment also protects the heart from ischemic reperfusion [77] , and oxypurinol, an allopurinol derivative, improves the left ventricular ejection fraction (LVEF) in congestive heart failure patients with low LVEF [22] . Despite the numerous aforementioned studies, several studies have indicated that no association between UA and ischemic stroke [78] or heart disease [79] exists.…”

Section: Nephropathymentioning

confidence: 99%

Linking uric acid metabolism to diabetic complications

Kushiyama

Tanaka

Hara

et al. 2014

WJD

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Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/ XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.Kushiyama A, Tanaka K, Hara S, Kawazu S. Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6): 787-795 Available from:

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The Effect of Xanthine Oxidase Inhibition Upon Ejection Fraction in Heart Failure Patients: La Plata Study

Cited by 104 publications

References 33 publications

Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction

Serum uric acid is associated with cardiac diastolic dysfunction among women with preserved ejection fraction

Uric Acid-Lowering Treatment With Benzbromarone in Patients With Heart Failure

Linking uric acid metabolism to diabetic complications

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