Clinical implications of longitudinally assessed uric acid in heart failure.

Background and aims: Numerous studies have evaluated the association between baseline uric acid (UA) and heart failure (HF) outcomes. The impact of longitudinal UA on HF survival remains unknown. We aim to investigate the association between different parameterizations of longitudinal UA measurements and survival outcomes in HF patients.

Methods and results: We retrospectively included patients hospitalized for HF with multiple repeated UA measurements. Joint models were fitted to assess the longitudinal association between UA and outcomes of all-cause and cardiovascular (CV) death. The study included 1596 patients (mean age 54 years, 26.9 % women) with 7875 UA measurements. During a median follow-up of 34.7 months, 330 all-cause deaths occurred, among them 280 of CV causes. After adjusting for clinically relevant covariates, every doubling of UA at any time led to a 5.14-fold increase of all-cause death risk (95 % confidence interval [CI] 3.79-8.29) and a 4.56-fold increase of CV death risk (95 % CI 2.96-8.29) for men; for women, the corresponding hazard ratios were 4.47 for all-cause death (95 % CI 3.02-7.40) and 4.93 for CV death (95 % CI 2.78-8.58). The increase in slope and area under the UA trajectory were additionally associated with a higher risk of all-cause and CV death in both genders. All the associations remained consistent after adjusting for repeatedly measured renal function and across the ejection fraction phenotypes.

Conclusion: The longitudinally measured UA and its derived parameterizations are strong prognostic factors in hospitalized HF patients, independent of clinically relevant confounders and repeatedly assessed renal function.