Association of Cystatin C- and Creatinine-Based eGFR With Adverse Outcomes in Heart Failure With Preserved Ejection Fraction
Kidney Medicine, 2026
Roehm B., Zhang X., Yang J., Haley J., Grodin J., Hedayati S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Patient Stratification | Serum |  Olink Target 96 |
Abstract
Rationale and Objective
Cystatin C- vs. creatinine-based measures of estimated glomerular filtration rate (eGFR) are more predictive of worse outcomes in people with heart failure with reduced ejection fraction (HFrEF). It is unknown if cystatin C-based measures may also yield more accurate prognoses in heart failure with preserved ejection fraction (HFpEF).
Study Design
Longitudinal analysis of people with HFpEF
Setting & Participants
214 participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial with available serum at baseline and 12 months in the National Heart, Lung, and Blood Institute’s Biologic Specimen and Data Repository Information Coordinating Center.
Exposures
Baseline, time-varying, or change over 12 months in eGFRcr, eGFRcys, and eGFRcr-cys
Outcomes
Composite of aborted cardiac arrest, heart failure hospitalization, or CV death.
Analytical Approach
Fine-Gray and joint models.
Results
Median follow-up was (IQR) 3.09 (2.07, 4.44) years. All 3 baseline eGFR measures were independently associated with the risk of the composite endpoint, after adjustment for race, diabetes mellitus, and BMI: HR (95% CI) per 5ml/min/1.73m2 lower eGFR: eGFRcr, 1.16 (1.04-1.28); eGFRcys, 1.20 (1.08-1.34); eGFRcr-cys, 1.19 (1.08-1.32). After adjusting for NT-proBNP and age, no baseline eGFR measure was statistically significantly associated with the composite endpoint. Only a relative decline in eGFRcr-cys from baseline to 12 months was associated with the composite endpoint in fully-adjusted models: eGFRcr-cys, HR 1.31 (1.02-1.67); per 10% eGFR decrease). Lower eGFR at any timepoint, using all 3 measures, was associated with the composite endpoint in fully-adjusted models.
Limitations
small number of events, possible survival bias
Conclusions
A decline in eGFRcr-cys from baseline to 12 months is associated with adverse cardiovascular outcomes in people with HFrEF. Measures of eGFR that incorporate only cystatin C may not be of greater prognostic value in people with HFpEF than measures that also incorporate serum creatinine.