Chronic hyperuricemia, uric acid deposit and cardiovascular risk

Abstract

Hyperuricemia is commonly associated with traditional risk factors such as dysglicemia, dyslipidemia, central obesity and abnormal blood pressure, i.e. the metabolic syndrome. Concordantly, recent studies have revived the controversy over the role of circulating uric acid, hyperuricemia, and gout as an independent prognostic factor for cardiovascular morbidity and mortality. In this regard, different studies also evaluated the possible role of xanthine inhibitors in inducing blood pressure reduction, increment in flow-mediated dilation, and improved cardiovascular prognosis in various patient settings. The vast majority of these studies have been conducted with either allopurinol or its active metabolite oxypurinol, i.e. two purine-like non-selective inhibitors of xanthine oxidase. More recently, the role of uric acid as a risk factor for cardiovascular disease and the possible protective role exerted by reduction of hyperuricemia to normal level have been evaluated by the use of febuxostat, a selective, non purine-like xanthine oxidase inhibitor. In this review, we will report current evidence on hyperuricemia in cardiovascular disease. The value of uric acid as a biomarker and as a potential therapeutic target for tailored old and novel "cardiometabolic" treatments will be also discussed.

Fig. (1)

Prevalence of hyperuricemia and gout in the US population in the last two available National Health and Nutrition Examination Surveys. Of note, mean uric acid levels were in the whole male and female populations = 6.14 mg/dl and 4.87 mg/dL, respectively, thus implying marked increments in both hyperuricemia and gout during the last decade (inset). Modified from ref .

Fig. (2)

Negative interaction between thrifty genes and environment leads to the progressive appearance of a constellation of risk factors, including hyperuricemia with and without urate deposits. Claudio Ferri, personal drawing.

Fig. (3)

In the FACT study febuxostat reduced serum uric acid levels more than allopurinol in gouty patients with elevated serum uric acid levels. Primary endpoint was the achievement of a serum uric acid level < 6 mg/dL in at least 3 monthly measurements. Modified from ref .

Fig. (4)

APEX trial: Patients with last 3 monthly serum urate levels <6.0 mg/dl in the intent-to-treat population. Treatment groups that were statistically significantly different for all patients were also statistically significantly different when the subset of patients with normal renal function was considered. * Ten patients received 100 mg and 258 subjects received 300 mg of allopurinol based on renal function. versus allopurinol in patients with impaired renal function; a = p < 0.05 versus allopurinol in all patients; b = p < 0.001 versus febuxostat 120 mg in all patients. c = p < 0.001 Modified from ref .