Failure to Achieve Serum Urate Target Increases Death Risk in Gout
CHICAGO — Patients with gout who fail to reach a serum urate target level of 6 mg/dL have a higher risk for death, according to Fernando Perez Ruiz, MD, PhD, of the BioCruces Health Research Institute in Spain.
“Some years ago, we published preliminary data from a cohort of 700 patients with gout, showing that severity of gout, namely tophaceous gout with showing subcutaneous sulfides, was associated with an increased risk for mortality independent of other known cardiovascular risk factors,” Perez Ruiz said, addressing attendees at the ACR/ARHP 2018 Annual Meeting. “At that time, the message was a negative one and not a positive one, saying that if you have severe gout, there is no effect of treatment on the outcome. We were discouraged by those results, but other investigators encouraged us to get more patients for a follow-up cohort, for a longer time, and have a look at what happened.”
For their new, follow-up cohort study, Perez Ruiz and colleagues aimed to determine whether lowering serum urate acid levels to less than 6 mg/dL would improve mortality risk among patients with gout. They recruited 1,193 patients treated at a gout clinic from 1992 to 2017, of whom 85% had an ultrasound- or microscope-confirmed diagnosis of gout. All included patients participated in at least one follow-up visit, during which serum uric acid levels were monitored. The average serum acid level until stabilization was used as the primary exposure, defined as less than 6 mg/dL vs. more than 6 mg/dL.
The researchers recorded patient mortality using medical records, reports from the patients’ families and local death registries. Variables and cofounders included age, sex, BMI, prior use of urate-lowering drugs, the number of affected joints at baseline, subcutaneous tophi, radiographic articular damage, number of annual flares prior to evaluation, previous cardiovascular disease diagnoses, the use of loop diuretics, alcohol intake, diabetes, hypertension, hyperlipidemia and impaired renal function.
According to the researchers, the mean serum uric acid level at baseline was 9.1 mg/dL. In addition, 16.3% of participants sustained serum uric acid levels of 6 mg/dL or more despite treatment. A total of 158 patients died during the study, representing an overall mortality rate of 13%. In addition, 24% of participants were lost to follow-up. Overall, the researchers calculated a crude mortality rate of 32.7 per 1,000 patient-years. This rate was significantly higher among patients with serum uric acid levels of more than 6 mg/dL, at 80.9 per 1,000 person-years.
After adjusting for age, sex, previous cardiovascular events and baseline serum uric acid concentration, a serum uric acid level of 6 mg/dL or higher was associated with increased risk for death (HR = 2.39; 95% CI, 1.64-3.5). Failure to reach this target was an independent predictor of mortality.
“These results are encouraging for both patients and clinicians,” Rubinstein said. “We should make every effort we can to reach that target. This kind of strategy is not new — we do it for diabetes, for hypertension and for hyperlipidemia, and for the first time, I think we can do it with gout.” – by Jason Laday
Perez Ruiz F. “Abstract 869. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.
Disclosure: Perez Ruiz reports speaking and advisory fees from Astra Zeneca, Grünenthal, Horizon and Menarini.