Failure to Lower Serum Urate in Gout Linked with Mortality

(Foot with gout. ©joloeiShutterstock.com)

Failure to achieve a target serum urate level of below 6 mg/dL among patients with gout is an independent predictor of total and cardiovascular-related mortality, say researchers writing in RMD Open: Rheumatic & Musculoskeletal Diseases this month.

A large body of evidence suggests that gout, the most common inflammatory arthritis in men and one of the most common causes of arthritis in elderly women, is a major determinant of total and cardiovascular mortality. This risk increases with the severity of the gout. High baseline serum urate levels plus tophi are associated with elevated mortality, suggesting a link between greater total body urate load and cardiovascular disease. However, the effects on mortality of the internationally recommended treat-to-target approach, with patients advised to achieve a serum urate level below 6 mg/dL (0.36 mmol/L), have not been established.

In this prospective cohort study, which recruited 1193 patients from 1992 to 2017, researchers aimed to determine the impact of achieving serum urate level below 6 mg/dL on overall and cardiovascular mortality in patients with gout.

Exposure was defined as the average serum urate level recorded during the first year of follow-up, dichotomized as ≤ or >6 mg/dL. Of the participants, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean serum urate level of 9.1 mg/dL at baseline, and a mean follow-up 48 months; and 158 died.

The risks of overall and cardiovascular mortality were significantly elevated for patients who failed to achieve target serum urate concentrations of 6 mg/dL.

“These risks were substantial with over twofold higher mortality compared with similar patients with gout who met target serum urate levels and were not accounted for by demographic or clinical factors,” wrote the authors, led by Fernando Pérez Ruiz, M.D., Ph.D., of Hospital Universitario Cruces in Barakaldo, Spain.

Crude mortality rates were significantly higher for a serum urate level of ≥6 mg/dL, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for a serum urate level of <6 mg/dL, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, cardiovascular risk factors, previous cardiovascular events, observation period and baseline serum urate concentration, a serum urate level of ≥6 mg/dL was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and cardiovascular mortality (HR=2.05, 95% CI 1.21 to 3.45).

“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. This positive benefit also extended to lower rates of cardiovascular death, although the level of significance was less likely related to the smaller event rate,” the authors wrote.

Gouty erosions as detected on X-ray were independently predictive of mortality, but gouty tophi detected from clinical examination were not, which, according to the authors, may suggest that erosive radiological changes indicate greater severity of inflammation and urate burden than tophi alone. Meanwhile, serum urate levels in the follow-up period, beyond baseline levels, continued to exert a significant predictive impact on future mortality, representing the continued risk of long-standing hyperuricemia.

“Achieving and maintaining a serum uric acid target below normal levels (<0.36 mmol/L or 6 mg/dL) in the first year reduces the risk of dying substantially.”

“Lower uric acid level targets should be recommended for hyperuricemic patients with gout. This information may help increase adherence to treatment if well explained to patients,” the authors wrote.

REFERENCE

Fernando Pérez Ruiz, Pascal Richette, Austin G Stack, 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.” RMD Open. October 13, 2019. doi: 10.1136/rmdopen-2019-001015