Assessing the Risk of Recurrent Gout Using Serum Urate Level

More than 12 million adults in the United States are affected by gout. There are associations between episodes of acute gout and severe pain, and reductions in quality of life, as well as a transient increase in major cardiovascular and venous thrombotic events. Accumulation of monosodium urate crystallization in the joints, often due to chronic hyperuricemia, is the primary cause of acute gout. 

According to Natalie McCormick, PhD, and colleagues, there are few data available on the associations between serum urate levels and the risk of recurrent gout among patients with a history of gout. The researchers conducted a retrospective study of patients with a history of gout treated in the primary care setting to identify the associations between baseline serum urate levels and subsequent episodes of acute gout, including acute gout requiring hospitalization. Results were reported in JAMA. 

The study cohort included patients in the United Kingdom with a history of gout between 2006 and 2010 who were followed up through Primary Care Linked Data medical record linkage through 2017 and through the Hospital Episode Statistics database until 2020. The study exposure was serum urate level at baseline. The primary outcome of interest was the rate of recurrent acute gout, assessed by hospitalization, outpatient, and prescription records, and adjusted rate ratios using negative binomial regressions. 

Based on population studies for incident gout risk among individuals without gout at baseline, serum urate levels were categorized as: (1) <6.0 mg/dL; (2) 6.0 to 6.9 mg/dL; (3) 7.0 to 7.9 mg/dL; (4) 8.0 to 8.9 mg/dL; (5) 9.0 to 9.0 mg/dL; and (6) ≥10.0 mg/dL. A serum urate level <6.0 mg/dL served as the reference group. 

Following exclusion of patients with missing covariate values for body mass index (BMI) and estimated glomerular filtration rate (n=21), the final study cohort included 3613 individuals from the UK database who had a history of gout and underwent measurement of serum urate between April 28, 2007, and September 29, 2019. Of the 3613 study participants, 86% (n=3104) were men and the mean age was 60 years. At baseline, the mean serum urate level was 6.87 mg/dL. 

There were associations between higher serum urate categories and male sex, higher BMI, greater alcohol consumption, smoking, greater intake of red meat, and the presence of chronic kidney disease (CKD). There were also associations between lower serum urate categories and older age and use of urate-lowering therapy. 

Follow-up continued for a mean of 8.3 years. During follow-up, there were 1773 new episodes of gout treated in the primary care setting or requiring hospitalization. Of the 3613 study participants, 72% had zero acute gout episodes, 16% had one acute gout episode, 6% had two acute gout episodes, and 5% had at least three acute gout episodes. Overall, 95% (n=1679/1773) of acute gout episodes occurred in patients with baseline serum urate ≥6 mg/dL and 98% (n=1731/1773) in those with baseline serum urate ≥5 mg/dL. 

There were associations between serum urate levels and recurrent gout in a graded manner. Following adjustment of rate ratios (RRs) for age, sex, and race, the rates of acute gout flares per 1000 person-years were 10.6 for those with baseline urate levels <6 mg/dL (adjusted RR, 1.0), 40.1 for levels of 6.0 to 6.9 mg/dL (adjusted RR, 3.37; 95% CI, 2.60-4.39), 82.0 for levels of 7.0 to 7.9 mg/dL (adjusted RR, 6.93; 95% CI, 5.43-8.84), 101.3 for levels of 8.0 to 8.9 mg/dL (adjusted RR, 8.67; 95% CI, 6.74-11.14), 125.3 for levels of 9.0 to 9.9 mg/dL (adjusted RR, 10.81; 95% CI, 8.02-14.56), and 132.8 for levels ≥10 mg/dL (adjusted RR, 11.42; 95% CI, 7.72-16.90); P for trend <.001. 

Following further adjustment for BMI; smoking status; consumption of alcohol, coffee, red meat, fish, and poultry; use of diuretic and urate-lowering therapy; and diabetes, cardiovascular disease, hypertension, and CKD, the corresponding RRs were 1.00, 3.16, 6.20, 7.77, 9.80, and 11.26 (95% CI, 7.47-16.97), respectively; P for trend <.001. There was an association between each increase in serum urate of 1 mg/dL and a 61% increase in recurrent flare rate (RR, 1.61; 95% CI, 1.54-1.68). In the fully adjusted model, the corresponding RR was 1.58 (95% CI, 1.50-1.66) per mg/dL. 

The RRs of flares were 1.00, 3.37, 6.93, 8.67, 10.81, and 11.42, respectively, over 10 years. Associations between baseline serum urate level and flare rate were similar among subsets defined by sex, race, presence of CKD, diuretic use, and urate-lowering therapy. 

There were 64 documented hospitalizations with gout as the primary discharge diagnosis. Of those, 62 (97%; 95% CI, 93%-100%) occurred in individuals with baseline serum urate ≥6 mg/dL and all 64 (100%; 95% CI, 94%-100%) occurred in those with baseline serum urate ≥5 mg/dL. The rates of hospitalization for gout (and RRs adjusted for age, sex, and race) per 1000 person-years were 0.18 for serum urate ≤6.0 mg/dL (adjusted RR, 1.0), 0.97 for serum urate 6.0 to 6.9 mg/dL (adjusted RR, 4.70; 95% CI, 0.98-22.53), 1.8 for serum urate 7.0 to 7.9 (adjusted RR, 8.94; 95% CI, 2.03-39.39), 2.2 for serum urate 8.0 to 8.9 mg/dL (adjusted RR, 10.37; 95% CI, 2.31-46.62), 6.7 for serum urate 9.0 to 9.9 (adjusted RR, 33.92; 95% CI, 7.50-153.36), and 9.7 for serum urate ≥10 mg/dL (adjusted RR, 45.29; 95% CI, 9.01-227.70). 

The researchers cited some limitations to the study findings, including the inability to measure acute gout flares that were not treated by medical personnel, the relatively small size of some of the subgroups, and the study design that may have led to confounding. 

In conclusion, the researchers said, “In this retrospective study of patients with history of gout, serum urate levels at baseline were associated with the risk of subsequent gout flares and with rates of hospitalization for recurrent gout. These findings support using a baseline serum urate [value] to assess risk of recurrent gout over nearly 10 years of follow-up.” 

Source: JAMA