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Hyperuricemia and mortality in heart failure: Is it time to change the route?

Published:January 21, 2020DOI:https://doi.org/10.1016/j.ejim.2020.01.005
      The prevalence of heart failure (HF) is increasing worldwide and in particular in the industrialized countries [
      • Yancy C.W
      • et al.
      ACC/AHA/HFSA focused update of the 2013 accf/aha guideline for the management of heart failure: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart failure society of america.
      ,
      • Ponikowski P
      • et al.
      ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (ESC)Developed with the special contribution of the heart failure association (HFA) of the esc.
      . This is associated with a parallel increase in the rate of hyperuricemia and gout [
      • Zhu Y.
      • Pandya B.J.
      • Choi H.K.
      Prevalence of gout and hyperuricemia in the us general population: the national health and nutrition examination survey 2007-2008.
      ,
      • Yamanaka H.
      Japanese society of, G. & nucleic acid, M. japanese guideline for the management of hyperuricemia and gout: second edition.
      that occurs with a high rate of hypertension, chronic kidney disease, atrial fibrillation, metabolic syndrome, diabetes, dyslipidemia, and obesity [
      • Borghi C.
      • Agabiti-Rosei E.
      • Bardin T.
      • et al.
      Serum uric acid and the risk of cardiovascular and renal disease.
      ], leading to an overall increase in urate mediated cardiovascular risk. The close correlation between uric acid and HF is based on a complex pathophysiological mechanism that, probably, does not reflect a direct effect of elevated uric acid on left ventricular function, but rather involves the extensive activation of the enzyme xanthine-oxidase (XO) that is responsible for urate production and increased levels of oxidative stress [
      • Borghi C.
      • Desideri G.
      Urate-Lowering drugs and prevention of cardiovascular disease: the emerging role of xanthine oxidase inhibition.
      ]. In HF patients, serum uric acid is probably representative of XO levels or activity that can play an important role in the pathophysiologic process leading to heart failure through inflammatory damage and loss of vascular endothelial function. In practical terms, the overexpression of XO and related oxidative stress could be a potential mechanism for the identification of those HF patients where hyperuricemia can be associated with a poor clinical prognosis. The main problem is how to identify these patients across the heterogeneous population of patients with HF where the clinical diagnosis and the severity of the disease can be a major confounder due to the extensive interaction between HF severity, renal function and diuretic use.

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