LAUSR

Elevated serum uric acid levels have been progressively emerged as a powerful and independent risk factor for many cardiovascular diseases, including hypertension [1, 2], coronary artery disease [3, 4], stroke [5, 6] and congestive heart failure [7–9]. It has been also reported strong, positive and independent correlations between high-serum levels of uric acid and metabolic abnormalities, including hypercholesterolemia, atherogenic dyslipidaemia, obesity, metabolic syndrome, and diabetes [10, 11]. Additionally, high serum uric acid levels are able to predict progression from end-stage renal and heart failure and they have been related to worsen prognosis and increased risk of cardiovascular death in many observational studies [12]. On the other hand, several reports have demonstrated that reducing levels of serum uric acid levels with xanthine oxidase inhibitors was associated with better prognosis and improved event-free survival rate in different cardiovascular settings, including hypertension [13, 14], coronary artery disease [15, 16], and even congestive heart failure. On the basis of these consideration, high-serum levels of uric acid should never be neglected or ignored, independently by the clinical context or the clinical condition in which they are observed [17]. From a pathophysiological point of view, increased xanthine oxidase activity is able to produce high-serum levels of uric acid and abnormal concentration of reactive oxygen species (ROS) at both cardiac and circulating levels [18]. Increased ROS concentration may be responsible for peripheral vasoconstriction, abnormal excitation–contraction coupling, myocardial impairment, and development of left ventricular remodelling, and dysfunction. These maladaptive responses to oxidative stress can be frequently observed in the pathogenesis of congestive heart failure, and have been related to worsen prognosis and progression towards the end-stage of the disease. Thus, pharmacological interventions aimed at reducing high serum levels of uric acid should be paralleled by improved prognosis and better quality of life in patients with different degrees of congestive heart failure. Available evidence, however, reporting contrasting reports. In the Efficacy and Safety Study of Oxypurinol Added to Standard Therapy in Patients With New York Heart Association Class III–IV Congestive Heart Failure (OPT-CHF) study, about 400 patients with New York Heart Association (NYHA) functional class III–IV heart failure due to systolic dysfunction on optimal medical therapy, were randomized to receive oxypurinol (600 mg daily) or matching placebo [19]. After 24 weeks of treatment, no significant differences were observed in the incidence of the composite endpoint, including heart failure morbidity, mortality, and quality of life, although post hoc analyses seem to suggest that some beneficial effects may be observed in those patients with baseline high levels of uric acid in a manner correlating with the degree of serum uric acid reduction [19]. In the La Plata Study, about 60 patients with NYHA functional class II to III heart failure, were randomized to receive oxypurinol (600 mg daily) or matching placebo. After 1 month of treatment, left ventricular ejection fraction was significantly higher, although only in those patients with reduced left ventricular performance at baseline, without relevant differences in walking capacity. In the Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) study, about 250 patients with NYHA class III–IV heart failure and reduced left ventricular ejection fraction (less than 40%) were randomized to receive allopurinol (300 mg daily) or matching placebo [20]. After 24 weeks of treatment, there Commentary on the manuscript entitled Effects of allopurinol and febuxostat on cardiovascular mortality in elderly heart failure patients.