Elevated serum urate concentration and duration of exposure predict gout risk
medwireNews: Elevated serum urate levels are a strong, concentration-dependent predictor for incident gout, but duration of hyperuricemia and other factors also play a role, indicates a combined analysis of four cohorts.
Data on 18,889 gout-free participants of the ARIC, CARDIA, and the Original and Offspring cohorts of the Framingham Heart Study gave an overall cumulative incidence of gout of 0.6% by 3 years, 1.1% by 5 years, 2.4% by 10 years, and 3.2% by 15 years.
At each timepoint the cumulative incidence varied according to baseline serum urate concentrations, the researchers report. By 5 years, rates ranged from 0.33% for individuals with serum urate levels below 6 mg/dL to 26.0% for those with levels of 10 mg/dL or above.
By 10 years the corresponding rates were 0.79% to 40.0%, and, by 15 years, a respective 1.1% to 49.0%.
Nicola Dalbeth (University of Auckland, New Zealand) and colleagues believe their estimates “may guide discussions with individuals with hyperuricaemia about their risk of developing gout over time.”
Based on the 5-year data, the researchers calculated that the incidence of gout was 9.8 per 1000 person–years for patients with baseline urate levels of 7 mg/dL or above, increasing to 20.0, 34.0, and 53.0 per 1000 person–years for those with levels of 8, 9, and 10 mg/dL or above.
But the researchers point out that as only about half of the individuals with serum urate levels of 10 mg/dL or above developed clinically evident gout over 15 years, there is “a role for additional factors in the pathogenesis of gout.”
They suggest in the Annals of the Rheumatic Diseases that such factors could be “inhibitors or promoters of crystal formation in the presence of elevated tissue urate concentrations and/or genetic and environmental factors that influence the inflammatory response to deposited crystals.”
Cox proportional hazards analysis showed that baseline serum urate level was an independent risk factor for gout, with a hazard ratio of 64.0 for individuals with levels of 10 mg/dL or above compared with those with levels below 6 mg/dL.
But in addition to elevated serum urate level, male sex, older age, and non-White ethnicity also significantly predicted an increased risk for gout.
The researchers comment on the sex difference, finding that women had a lower risk for gout at all timepoints compared with men, but this difference reduced over time.
“The duration of exposure to elevated urate concentrations may be different in women,” they suggest, “as serum urate concentrations are generally lower before the menopause.”
They add: “Together with the increased risk with older age, these sex findings suggest that the duration of exposure to hyperuricaemia contributes to the development of gout.”
There was also a small percentage of individuals who despite having baseline serum urate levels below 6 mg/dL subsequently developed gout, an occurrence they suggest may be “due to local tissue factors that influence urate solubility, crystal nucleation or crystal growth.”
By Lucy Piper
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