The most recent European League Against Rheumatism (EULAR) recommendations for gout advise against maintaining serum urate (SU) < 3 mg/dL for prolonged periods. While several Asian cohort studies reported higher mortality in individuals with extremely low SU, non‐Asian data are scarce, and the relationship between hypouricemia, cardiovascular risk, and mortality remains unclear.
We calculated multivariable hazard ratios (HR) compared to a referent SU level of 5‐6 mg/dL for SU categories <4, 4‐5, 6‐7, 7‐8, and >8 mg/dL in men and <3, 3‐4, 4‐5, 6‐7, >7 mg/dL in women. Among women, there was no higher mortality risk at SU <3 mg/dL (HR 1.09, 95% confidence interval [CI] 0.92 to 1.28). Among men, there was a 28% higher mortality risk at SU<4 mg/dL (HR 1.28, 95% CI 1.13 to 1.45), with nearly three‐times higher mortality from diabetes (HR 2.89, 95% CI 1.59 to 5.23), but no increase in mortality from any other specific cause.
In conclusion, no long‐term excess mortality risk was found among US women with SU as low as <3 mg/dL, which is incompatible with causality between hypouricemia and premature mortality in women. We found excess all‐cause and diabetes‐related mortality among hypouricemic US men, which may, in part, be attributable to the uricosuric effect of hyperglycemia in fatal uncontrolled diabetes.