Uric Acid Variability Is Associated with Poor Prognosis in Heart Failure

Abstract

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.