SERUM URIC ACID PREDICTS HEART FAILURE IN A LARGE ITALIAN COHORT. SEARCH FOR A CUT-OFF VALUE The URRAH (URic acid Right for heArt Health) study

Objective : to assess the prognostic cut-off values of serum uric acid (SUA) in
predicting fatal and morbid heart failure (HF) in a large Italian cohort in the frame of the
Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of
Hypertension.
Methods : The UR ic acid R ight for he A rt H ealth ( URRAH ) study is a
nationwide, multicentre, observational cohort study involving data on subjects aged 18
to 95 years, recruited on a community basis from all regions of Italy under the
patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ±
65 months. Incident HF was defined on the basis of ICD10 codes and double-checked
with general practitioners and hospital files. Multivariate Cox regression models having
fatal and morbid HF as dependent variables, adjusted for age, sex, systolic blood
pressure, diabetes, hematocrit, LDL-cholesterol, smoking and estimated GFR were
used to search for an association between SUA as a continuous variable and HF. By
means of receiver operating curves (ROC) two prognostic cut-off values (one for all HF
and one for fatal HF) were identified as able to discriminate between subjects doomed
to develop the event. These cut-off values were used as independent predictors to
divide subjects into those < cut-off and > cut-off in a multivariate Cox models, adjusted
for the confounders.
Results : A total of 21,386 subjects were included in the analysis. In Cox analysis,
SUA as a continuous variable was a significant predictor of all [hazard ratio, HR 1.29
(1.23–1.359), p < 0.0001] and fatal [HR 1.268 (1.121–1.35), p< 0.0001] incident HF.
Cut-off values of SUA able to discriminate all and fatal HF status were identified by
mean of ROC curves in the whole database: SUA > 5.34 mg/dL (CI 4.37 to 5.6,
sensitivity 52.32, specificity 63.96, p < 0.0001) was the univariate prognostic cut-off
value for all HF, while SUA > 4.89 mg/dl (CI 4.78 to 5.78, sensitivity 68.29, specificity
49.11, p < 0.0001) for fatal HF.
The cut-off for all HF and the cut-off value for fatal HF were accepted as independent
predictors in the Cox analysis model, the hazard ratios being 1.645 (1.284 - 2.109, p <
0.0001) for all HF and 1.645 (1.284 - 2.109, p < 0.0001) for fatal HF.
Conclusions : The results of the present study confirm that SUA is an independent risk
factor for all HF and fatal HF, after adjusting for potential confounding variables, and
demonstrate that a prognostic cut-off value can be identified for all HF (>5.34 mg/dl)
and for fatal HF (>4.89 mg/dl).