Uric acid in chronic heart failure: a marker of chronic inflammation

Leyva, Francisco

doi:10.1053/euhj.1998.1188

Cited by 258 publications

(189 citation statements)

References 61 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…23 In CHF, UA levels relate to the degree of inflammatory activation. 24 In this context, it was shown in a mouse model that UA infusion causes increased endotoxin-stimulated production of tumor necrosis factor-␣. 12 Tumor necrosis factor-␣, in turn, can contribute to vascular damage.…”

Section: Onoomentioning

confidence: 99%

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

et al. 2002

View full text Add to dashboard Cite

Background-In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. Methods and Results-In 10 CHF patients with normal serum uric acid (UA) levels (315Ϯ42 mol/L) and 9 patients with elevated UA (535Ϯ54 mol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 g/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (PϽ0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558Ϯ21 mol/L, range 455 to 743 mol/L), treatment reduced UA by Ͼ120 mol/L in all patients (mean reduction 217Ϯ15 mol/L, PϽ0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (ϩ24%, Pϭ0.027) and legs (ϩ23%, Pϭ0.029). Flow-dependent flow improved by 58% in arms (Pϭ0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (PϽ0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (rϭ0.63, PϽ0.05). Conclusions-In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.

show abstract

Section: Onoomentioning

confidence: 99%

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

et al. 2002

View full text Add to dashboard Cite

show abstract

“…In CHF, hyperuricemia (independent of kidney function and diuretic dose) is a marker of impaired oxidative metabolism and hyperinsulinemia, 4 -6 inflammatory cytokine activation, 7 and impaired vascular function. 8,9 The relationship of UA to kidney function and diuretic dose may additionally increase the value of UA as prognostic marker.…”

Section: See P 1951mentioning

confidence: 99%

Uric Acid and Survival in Chronic Heart Failure

et al. 2003

View full text Add to dashboard Cite

Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results-For the derivation study, 112 patients with CHF (age 59Ϯ12 years, peak oxygen consumption [V O 2 ] 17Ϯ7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (nϭ182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (nϭ120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 mol/L (9.50 mg/dL) (independently of age, peak V O 2 , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; PϽ0.0001). In the validation study, UA Ն565 mol/L predicted mortality (hazard ratio, 7.14; PϽ0.0001). In 16 patients (from both studies) with UA Ն565 mol/L, left ventricular ejection fraction Յ25% and peak V O 2 Յ14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, PϽ0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions-High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.

show abstract

“…3,8 Recent studies have demonstrated that an elevated serum uric acid level is also associated with circulating levels of systemic inflammatory mediators in a variety of conditions, including congestive heart failure. 9 Although uric acid has been generally considered inert, there is evidence that soluble uric acid can induce VSMC proliferation in vitro. 10 Recent studies have shown that uric acid-induced VSMC proliferation is mediated by the activation or induction of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPK), cyclooxygenase-2 (COX-2), and platelet-derived growth factor (PDGF).…”

mentioning

confidence: 99%

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

et al. 2003

View full text Add to dashboard Cite

Abstract-Previous studies have reported that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation in vitro. We hypothesized that uric acid may also have direct proinflammatory effects on VSMCs. Crystal-and endotoxin-free uric acid was found to increase VSMC monocyte chemoattractant protein-1 (MCP-1) expression in a time-and dose-dependent manner, peaking at 24 hours. Increased mRNA and protein expression occurred as early as 3 hours after uric acid incubation and was partially dependent on posttranscriptional modification of MCP-1 mRNA. In addition, uric acid activated the transcription factors nuclear factor-B and activator protein-1, as well as the MAPK signaling molecules ERK p44/42 and p38, and increased cyclooxygenase-2 (COX-2) mRNA expression. Inhibition of p38 (with SB 203580), ERK 44/42 (with UO126 or PD 98059), or COX-2 (with NS398) each significantly suppressed uric acid-induced MCP-1 expression at 24 hours, implicating these pathways in the response to uric acid. The ability of both N-acetyl-cysteine and diphenyleneionium (antioxidants) to inhibit uric acid-induced MCP-1 production suggested involvement of intracellular redox pathways. Uric acid regulates critical proinflammatory pathways in VSMCs, suggesting it may have a role in the vascular changes associated with hypertension and vascular disease.

show abstract

Uric acid in chronic heart failure: a marker of chronic inflammation

Cited by 258 publications

References 61 publications

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart Failure

Uric Acid and Survival in Chronic Heart Failure

Uric Acid Stimulates Monocyte Chemoattractant Protein-1 Production in Vascular Smooth Muscle Cells Via Mitogen-Activated Protein Kinase and Cyclooxygenase-2

Contact Info

Product

Resources

About