# Uric Acid Variability Is Associated with Poor Prognosis in Heart Failure

**Authors:** Viana Copeland, Shir Elimeleh, Assi Milwidsky, Noam Makmal, Ranel Loutati, Boris Fishman, Yishay Wasserstrum, Moti Zwilling, Elad Maor, Ehud Grossman

PMC · DOI: 10.3390/jcm15062330 · Journal of Clinical Medicine · 2026-03-18

## TL;DR

Fluctuating uric acid levels in heart failure patients are linked to worse outcomes, suggesting that tracking these changes could help predict and manage the disease better.

## Contribution

This study demonstrates that uric acid variability, not just its average level, is independently associated with mortality and hospitalization in heart failure patients.

## Key findings

- Low uric acid variability was associated with reduced mortality and hospitalization risks in heart failure patients.
- High uric acid variability was linked to increased mortality and hospitalization risks, even after adjusting for other factors.
- The association between uric acid variability and outcomes remained consistent across different heart failure subgroups.

## 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.

## Linked entities

- **Chemicals:** uric acid (PubChem CID 1175)
- **Diseases:** heart failure (MONDO:0005252)

## Full-text entities

- **Diseases:** HF (MESH:D006333), died (MESH:D003643)
- **Chemicals:** UA (MESH:D014527)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026695/full.md

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Source: https://tomesphere.com/paper/PMC13026695