Uric acid as a predictor of all-cause mortality in heart failure: a meta-analysis

Serum uric acid (SUA) is a product of xanthine oxidase (XO). Apoptosis and tissue hypoxia lead to increased purine catabolism, which, in turn, increases XO activity and subsequently SUA levels. The purpose of this study was to perform a meta-analysis to evaluate the evidence supporting SUA as a predictor of all-cause mortality in patients with heart failure (HF) and to determine the SUA cut-off for the increase in risk. A search of the MEDLINE database (1966 to March 2009) supplemented by manual searches of bibliographies of key relevant articles was performed. The authors selected all cohort studies in which SUA was measured and mortality was reported in patients with HF. The pooled relative risk (RR) with the corresponding 95% confidence interval (CI) for all-cause mortality using the fixed-effects method was calculated. The effects of SUA on all-cause mortality at different SUA cut-offs using meta-regression was evaluated. The search strategy yielded 358 studies, of which only 6 met our eligibility criteria. The studies, however, comprised 1456 evaluable patients with HF, with a median ejection fraction of 32% (range, 26%-40%). The RR of all-cause mortality was 2.13 (95% CI, 1.78-2.55) for SUA>6.5 mg/dL compared with <6.5 mg/dL SUA level. There was a linear association (P<.01) between SUA and mortality after 7 mg/dL. Uric acid is an important prognostic marker for all-cause mortality in HF. SUA levels >7 mg/dL are associated with higher all-cause mortality.