Serum Urate Strong, Imperfect Predictor of Subsequent Gout

Janis C. Kelly

March 14, 2018

Although baseline serum urate concentration was a strong, concentration-dependent predictor of incident gout, less than half of patients with high levels developed clinically evident gout within 15 years, according to a large report.

Nicola Dalbeth, MBChB, MD, from the University of Auckland, New Zealand, and colleagues report their findings in an article published online February 28 in Arthritis and Rheumatic Diseases.

Women with high serum uric acid (SUA) levels had a lower cumulative incidence of gout than men with similar SUA levels at 3 years of follow-up, but were at similar risk at 10 and 15 years.

The researchers analyzed individual participant data from four publicly available cohorts: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, and both the original and offspring cohorts of the Framingham Heart Study.

All patients were gout-free at baseline. Mean follow-up was 11.2 years, and there were 212,363 total patient-years of follow-up. The researchers defined gout using recognized classification criteria, physician diagnosis, patient self-report of disease, or self-report of physician diagnosis. They calculated cumulative gout incidence at 3 years, 5 years, 10 years, and 15 years after the baseline visit.

The 15-year cumulative incidence of gout ranged from 1.1% for participants with baseline SUA lower than 6 mg/dL to 49% for those with baseline SUA of 10 mg/dL or higher.

The researchers calculated hazard ratios (HRs) using Cox proportional hazard analysis, which showed that cohort, male sex, older age, nonwhite ethnicity, and baseline SUA were independent predictors for incident gout.

Compared with baseline SUA lower than 6 mg/dL, patients with baseline SUA from 6.0 to 6.9 mg/dL were nearly three times as likely to develop gout (adjusted HR [aHR], 2.7), and those with baseline SUA from 7.0 to 7.9 mg/dL were more than six times as likely (aHR, 6.6).

Participants with baseline SUA from 8.0 to 8.9 mg/dL were at 15 times higher risk (aHR, 15), those with baseline SUA from 9.0 to 9.9 mg/dL were at 30 times higher risk (aHR, 30), and those with baseline SUA 10 mg/dL or higher were more than 60 times as likely to develop gout (aHR, 64).

Regarding the influence of sex differences, the authors write, "While women had lower risk of incident gout compared with men for early time points, the risk according to serum urate level became similar between men and women with longer periods of observation. The duration of exposure to elevated urate concentrations may be different in women, as serum urate concentrations are generally lower before the menopause."

They note that both the increased risk associated with older age and the sex differences support the role of duration of exposure to hyperuricemia as a major factor in the development of gout.

The finding that even at the highest levels of baseline SUA, only 49% of subjects went on to develop clinically evident gout within 15 years highlights some major unknowns in gout pathogenesis.

"Our data indicate that the absolute risk of incident gout in those with modestly elevated serum urate concentrations is low, and even those with very high serum urate concentrations do not invariably develop gout, even over a prolonged period of follow-up," the authors explain.

"These observations imply a role for additional factors in the pathogenesis of gout; such factors would include 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."

The study was supported by the Health Research Council of New Zealand. Dalbeth reports receiving consulting fees, grants, or speaker fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea, Pfizer, Amgen, and Kowa outside of the submitted work. Other authors report receiving consulting fees from AstraZeneca, Pfizer, Horizon, and Ardea outside of the submitted work.

Ann Rheum Dis. Published online February 20, 2018. Abstract

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