Uric acid variability is associated with poor prognosis in heart failure

Introduction

Elevated UA levels correlate with worse HF outcomes, but past studies used single UA measurements. The effect of intra-individual UA fluctuations, beyond mean levels, is unclear.

Purpose

To assess the relationship between serum uric acid (UA) variability and adverse clinical outcomes in heart failure (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 and divided into quartiles: Q1 (≤0.69 mg/dL), Q2-Q3 (>0.69-<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 (PSM), and subgroup analyses were used to assess associations.

Results

Over a median follow-up of 4.3 years (IQR 1.6-7.7), 36% 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) (Figures 1 and 2). Consistent associations noted after PSM 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.

Figure 1: Adjusted Hazard Ratios for All-Cause Mortality by UA Variability Pre PSM- Adjusted Cox models comparing ≤Q1 vs Q2-Q3 and ≥Q4 vs Q2-Q3 UA variability evaluating mortality.

Figure 2: Cumulative HF Related Hospitalizations Based on UA Variability Pre PSM- Cumulative incidence functions for first HF-related hospitalization with death treated as a competing event, stratified by UA variability quartiles (Q1, Q2-Q3, Q4).All-Cause Mortality by UA VariabilityFor image description, please refer to the figure legend and surrounding text.HF Hospitalization by UA VariabilityFor image description, please refer to the figure legend and surrounding text.