Serum urate during follow-up of gout is not associated to mortality in the lowest stratum

 

Ana M. Herrero-Beites (1)0, Nerea Perez-Herrero (2), Fernando Perez-Ruiz (3)

 

Affiliation(s):

Gorliz Hospital (1), Deusto Medicine School (2), And Cruces University Hospital (3)

 

 

Background: late EULAR recommendations suggested to avoid serum urate (sUr) < 3 mg/dl in the long-term during treatment due to a possible association with mortality. The case is that hypouricemia is associated in real life to health states associated to high risk of mortality (cancer, severe diabetes, liver failure, severe neurologic diseases) and genetic disorders not associated to mortality (xanthinuria, familial hypouricemia types 1 &2).

Objective: analyze whether mortality is associated to different serum urate strata (including sUr < 3 mg/dl) during urate-lowering treatment, adjusted by other disease variables and comorbid conditions associated to mortality.

Method: analysis of a nested cohort of gout patients, prospectively recruited. General variables (age, gender), disease variables (time from onset, number of flares, number of joints involved, tophi, previous and prescribed urate lowering therapy, sUr at baseline and during follow-up, and comorbidity variables (Kaiser comorbidity strata, hypertension, hyperlipidemia, diabetes, CKD, vascular event) were available for analysis.

Variables plausibly associated (p<0.200) were selected using univariant Kaplan-Meier survival analysis, and then included in multivariate Cox proportional hazard survival analysis.

Results: sUr during follow-up was available for 1,618 patients with a follow-up of at least 3 months (range 3-228). sUr was considered as the lowest ever registered during follow-up. Age, female gender, tophi, number of flares, polyarticular distribution, previous ULT prescription, diabetes, previous vascular event, CKD 3-5, and sUr strata were associated in univariant survival analysis (Table 1).

Multivariate Cox survival analysis showed that age, female gender, higher comorbidity, tophi, baseline sUr, and the two highest sUr strata during follow-up were independently associated with mortality. (Table 2). 

The two lower sUr strata (<3 vs. 3-6 mg/dl) did not show differences in mortality, whereas the two higher (6-9 vs. > 9 mg/dl) were different from the two lower and also between them.

Conclusions: this analysis shows that serum urate levels during follow-up are associated to mortality. Higher uricemia strata, especially over 9 mg/dl, show higher mortality rates. Nevertheless, no difference is observed for patients with sUr < 3 mg/l compared to all other also on therapeutic target (3-6 mg/dl).