Dynamic Urinary Albumin/Creatinine Ratio Patterns Predict Adverse Outcomes in HFpEF: TOPCAT Cohort Analysis

Abstract

Background

Urinary albumin-to-creatinine ratio (uACR) is a recognized cardiovascular risk marker, but its dynamic changes in heart failure with preserved ejection fraction (HFpEF) remain underexplored. We aimed to identify distinct uACR trajectory patterns and their associations with clinical outcomes in HFpEF patients.

Methods

We analyzed 746 HFpEF patients with ≥ 3 uACR measurements from the TOPCAT trial. Latent Class Trajectory Modeling identified uACR patterns. The primary outcome was cardiovascular death, aborted cardiac arrest, or heart failure hospitalization. Cox proportional hazards models assessed associations between trajectories and outcomes.

Results

Three uACR trajectory patterns emerged: stable (70.5%), decreasing (16.5%), and fluctuating high (13.0%). The primary endpoint occurred in 15.02%, 25.20%, and 36.08% of patients, respectively (p < 0.001). In adjusted models, the fluctuating high group showed increased risk for the composite endpoint (HR 1.91, 95% CI 1.25–2.91) and heart failure hospitalization (HR 1.91, 95% CI 1.19–3.06), while the decreasing group showed an association with myocardial infarction based on few events (HR 3.00, 95% CI 1.33–6.76). Adding trajectory information produced a modest improvement in risk prediction (C-index 0.758 to 0.765; AUC 0.786 to 0.792 at 4 years and 0.832 to 0.845 at 6 years, p = 0.0149).

Conclusion

This study first identified distinct uACR trajectory patterns in HFpEF patients. The fluctuating high trajectory was associated with increased cardiovascular risk and heart failure hospitalization, while the association between the decreasing trajectory and myocardial infarction was exploratory and requires validation.