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).