Hyperuricemic patients who fail to achieve guideline-recommended serum uric acid target levels of less than 6 mg/dL are at increased risk for all-cause and cardiovascular (CV) mortality, according to new study findings.

The study included 1193 prevalent gout patients (mean age 60 years; 92% male) attending a Spanish specialty clinic during 1992 to 2017. Patients received colchicine prophylaxis (0.5 to 1 mg/d) for 6 to 12 months or prednisone (2.5 mg twice per day) and urate-lowering therapy. For first-line treatment, 62.2% received allopurinol, 17.9% benzbromarone, and 8.7% febuxostat; 11.2% received no treatment.

A total of 158 patients died over a mean follow-up of 48.6 months, including 82 from CV causes. Crude mortality rates were significantly higher for patients with serum uric levels of 6 mg/dL or higher than for those with lower levels: 80.9 vs 25.7 per 1000 patient-years. Compared with levels below 6 mg/dL, levels of 6 mg/dL or higher were significantly associated with 2.3- and 2.0-fold increased risks for all-cause and CV mortality, respectively, after adjusting for age, sex, CV risk factors, previous CV events, and observation period.

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“The findings from this study add credence to the hypothesis that elevated UA concentrations above 6 mg/dL contribute substantially to mortality and to shortened life spans,” Fernando Pérez-Ruiz, MD, PhD, of Hospital Universitario Cruces in Spain, and colleagues wrote in RMD Open: Rheumatic & Musculoskeletal Diseases.

Patients with tophi, diabetes, or history of previous CV event had higher risks for CV mortality in multivariable analysis. In the cohort, 1 in 3 patients had tophi and the same proportion had a previous CV event, whereas 1 in 5 had diabetes. Gouty erosions detected on radiography, rather than tophi themselves, predicted mortality, the researchers explained.

International guidelines recommend targeting serum urate levels to less than 6 mg/dL to reduce the frequency of morbidity and gout flares in patients, who experienced 3-4 flares, on average, in the previous year. The new findings indicate a survival benefit.

Urate-lowering therapy and strategies that reduce serum uric levels to less 6 mg/dL are likely to confer a survival advantage beyond gout control, according to the investigators.

Citing a possible mechanism described in a previous report published in Annals of Rheumatic Diseases, Dr Pérez-Ruiz and his collaborators explained that hyperuricemia causes a shift in the interleukin-1β/interleukin-1Ra balance produced by peripheral blood mononuclear cells after exposure to monosodium urate (MSU) crystals and toll-like receptors-mediated stimuli. This process may reinforce an enhanced state of chronic inflammation.

“In our study, we confirm the beneficial impact of allopurinol and benzbromarone in reducing overall mortality, as each of these was associated with improved survival,” Dr Ruiz’s team stated. The impact of urate-lowering therapy on cardiovascular events remains controversial, according to the investigators.

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Pérez Ruiz F, Richette P, Stack AG, et al. Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality [published online October 18, 2019]. RMD Open: Rheum & Musc Dis. 2019;5:e001015. doi:10.1136/rmdopen-2019-001015