Leveraging dynamic serum uric acid trajectories for risk stratification in hospitalized HFpEF patients

Single-timepoint SUA measurement provides limited prognostic insight in acute heart failure with preserved ejection fraction (HFpEF). This study assessed whether dynamic in-hospital SUA trajectories (using admission and pre-discharge measurements) are more strongly associated with long-term outcomes than static single-timepoint measures.

The cohort consisted of 4,164 acute HFpEF patients, drawn from the China Heart Failure Center Registry. The primary outcome was a major adverse cardiovascular events (MACE). SUA at admission and pre-discharge was analyzed as continuous using Cox regression. Patients were categorized to four dynamic trajectory groups according to admission and pre-discharge SUA (cut-off 7 mg/dL): persistently normal (N-N), escalating (N-H), de-escalating (H-N), and persistently elevated (H-H). The optimal prognostic SUA cut-off was determined by ROC analysis.

Over a median of 25.2 months, 900 patients (21.6%) experienced the primary outcome. Multivariable Cox regression showed that pre-discharge SUA (HR 1.23, 95% CI 1.18-1.29, p < 0.001), but not admission SUA (HR 1.04, 95% CI 0.98-1.10, p = 0.17) was independently associated with MACE. Relative to the N-N group, dynamic trajectory analysis revealed significantly increased risk for the N-H group (adjusted HR 1.56, 95% CI 1.02-2.40, p = 0.041) and the H-H group (adjusted HR 1.61, 95% CI 1.10-2.34, p = 0.014), whereas the H-N group did not show a significant difference. The AUC of pre-discharge SUA for discriminating MACE risk was 0.70, with 84.3% sensitivity and 45.9% specificity at the 5.6 mg/dL threshold derived from ROC analysis. Subgroup and sensitivity analyses confirmed the robustness of these associations (all p for interaction >0.05 for most subgroups; results unchanged after excluding urate-lowering therapy or using multiple imputation).

In hospitalized HFpEF patients, dynamic SUA trajectories are more strongly associated with MACE than single measurements. Identifying high-risk patterns prior to discharge may inform risk stratification and generate the hypothesis that nutritional or other modulatory strategies targeting SUA trajectories could be tested in future prospective studies to determine whether they improve outcomes.