Uric Acid Variability Is Associated with Poor Prognosis in Heart Failure

Aims: Elevated uric acid (UA) levels correlate with worse heart failure (HF) outcomes, but past studies used single UA measurements. The effect of intra-individual UA fluctuations, beyond mean levels, is unclear. This study assesses the relationship between serum UA variability and adverse clinical outcomes in HF patients. Methods: We analyzed 18,115 HF patients from the SHEBAHEART registry (2009-2025) with at least three UA measurements within three years of diagnosis. UA variability was quantified as the mean deviation (MD) from each patient's average UA level and divided into quartiles: Q1 (≤-0.69 mg/dL), Q2-Q3 (>-0.69 and <1.53 mg/dL, reference), and Q4 (≥1.53 mg/dL). All-cause mortality was the primary outcome and HF hospitalization was secondary. Cox regression, propensity score matching, and subgroup analyses were used. Results: Over a median follow-up of 4.3 years (IQR 1.6-7.7), 36% of patients were hospitalized for HF and 65.5% died. UA variability showed a graded association with outcomes. Low variability (Q1) was linked to reduced mortality (HR 0.79, 95% CI 0.75-0.83) and HF hospitalization (HR 0.84, 95% CI 0.79-0.90), while high variability (Q4) increased mortality (HR 1.58, 95% CI 1.51-1.69) and hospitalization risk (HR 1.17, 95% CI 1.10-1.25) (all p < 0.001). These associations remained after propensity score matching and across HF subgroups. Conclusions: UA variability is a robust, independent predictor of mortality and HF hospitalization. Serial UA monitoring may enhance risk stratification in HF management.