Abstract Body (Do not enter title and authors here): Background: Considering the high prevalence and comparable five-year mortality rates of heart failure with preserved ejection fraction (HFpEF) to heart failure with reduced ejection fraction (HFrEF), and the inconsistent results regarding prognostic biomarkers for HFpEF, we aim to systematically review studies evaluating the prognostic role of common kidney function markers in HFpEF.
Methods: Following PRISMA guidelines, a systematic search was performed in online databases from inception to March 2024. Studies that primarily assessed the association of blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), estimated glomerular filtration rate (eGFR), and cystatin-C with HFpEF outcomes were included. A random-effects meta-analysis was conducted to pool the hazard ratios (HRs) and their 95% confidence intervals (CIs) for a 1-unit increase in markers or higher levels versus lower levels for the incidence of adverse events, including all-cause mortality, HF readmission, cardiac mortality, and composite outcomes.
Results: Out of 2491 reviewed studies, 80 were included. A significant correlation between BUN levels and HFpEF outcomes, mainly HF readmission and all-cause mortality, was found. The meta-analysis showed that a 1-unit increase in BUN was linked to a higher hazard of these events (HR 1.02, 95% CI 1.01 to 1.03, P = 0.0003). A 1-unit increase in UA resulted in a higher incidence of adverse events (HR 1.13, 95% CI 1.05 to 1.21, P = 0.0005). Higher serum Cr levels were linked to increased all-cause mortality, with a 1-unit increase in Cr leading to a higher incidence of adverse events (HR 1.17, 95% CI 1.06 to 1.29, P = 0.0017). Higher eGFR values were associated with lower mortality and hospitalization (HR 0.99, 95% CI 0.98 to 0.99, P < 0.0001). The predictive value of cystatin-C was also demonstrated, with its increased levels correlating with higher mortality and readmission, showing a higher hazard ratio (compared to others) of 1.43 (95% CI 1.21 to 1.75, P < 0.0001). It appears that among continuous variables, cystatin-C works better to predict adverse outcomes in HFpEF (figure).
Conclusion: Renal function biomarkers play a significant role in predicting HFpEF outcomes, aiding in better risk assessment and patient management.