Gout, hyperuricemia and cardiovascular risk

Concern about gout-related increase in risk of hypertension and cardiovascular diseases has been raising in recent years. A similar relationship has been postulated even for asymptomatic hyperuricemia. The aims of this review are to appraise the available evidence about: i) the relationship between hyperuricemia itself and/or gout and cardiovascular diseases; ii) the effect of decreasing serum acid uric level on the rate of cardiovascular events. To meet this purpose, we did an extensive analysis of literature, limiting the search to articles in English, indexed in Medline and published in the last 17 years. Most of the retrieved studies were conducted on surrogate outcomes, whereas randomized trials on clinically relevant outcomes are few and of questionable quality. Based on the available data, we may conclude that hyperuricemia itself is a probable, although weak, risk factor for hypertension and increases the risk of nephropathy in patients with type 2 diabetes mellitus. Moreover, symptomatic gout significantly increases the risk of cardiovascular events, particularly of myocardial infarction and mainly in young-adult and people without other risk factors. Regarding the effectiveness of urate-lowering drugs in the prevention of myocardial infarction, the strongest evidence supports their use in subjects affected by gout. A probable efficacy in controlling hypertension, especially in young subjects and women, as well as in preventing nephropathy in type 2 diabetic patients has also been reported. Interestingly, allopurinol administered at doses <= 300 mg/day seems to protect from myocardial infarction, hypertension, total and serious cardiovascular events; preliminary evidence suggests a protective effect of febuxostat on major adverse cardiovascular events in high-risk gouty patients.