SERUM URIC ACID, INDEPENDENTLY OF ARTERIAL HYPERTENSION, PREDICTS NON-FATAL INCIDENT CEREBROVASCULAR EVENTS IN AN ITALIAN LARGE COHORT OF MEN AND WOMEN. SEARCH FOR A CUT-OFF VALUE

Abstract

Objective: Searching for a prognostic cut-off value of serum uric acid (SUA) for ischaemic stroke in a large regional-based Italian cohort of men and women in the frame of the URRAH study (URic Acid Right for heArt Health). Design and method: The large database URRAH collects data from cohorts epidemiological laboratories including subjects with at least one measure of SUA and a follow-up of ∼20 years. Incident ischaemic stroke was defined in 23,475 subjects on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having morbid and fatal stroke as dependent variables, adjusted for arterial hypertension (AH), age, sex, diabetes, hematocrit, LDL-Cholesterol, smoking, chronic renal disease, and haemotocrit, were preliminarily used to search for a predictive role of SUA as a continuous variable and stroke. Two prognostic cut-off values (one for morbid and one for fatal stroke), identified by means of receiver operating curves (ROC) and able to discriminate between subjects doomed to develop the event, were then used as independent predictors in further multivariate Cox models adjusted for the confounders listed above. Results: In Cox analysis, SUA was a significant predictor of morbid stroke [odds ratio 1.499 (1.033–1.278), p < 0.01], but not for fatal stroke, independently of AH. ROC showed that >4.20 mg/dl (95%CI, 3.36–6.05, sensitivity 75.1, specificity 31.1, p < 0.003) was a significant univariate cut-off of SUA for morbid stroke, and >5.70 mg/dl (CI >4.40 to >6.77, sensitivity 42.67, specificity 71.15, p < 0.01) at univariate cut-off for fatal stroke. Nevertheless, only the first one was accepted as a predictor in multivariate Cox analyses adjusted for the confounders listed above (hazard ratio 1.464, CI 1.019–2.103, p = 0.038), while the second one was rejected (p = 0.2). Conclusions: In conclusion, after adjustment for AH, age, diabetes and renal disease, a prognostic cut-off value of SUA for morbid ischaemic stroke (>4.20 mg/dl) does exist while fatal ischaemic stroke cannot be predicted by SUA.