What question did this study set out to answer?

The study aims to evaluate the predictive value of cystatin C for adverse outcomes in heart failure patients with normal to mild renal dysfunction across different ejection fractions.

April 22, 2026Open Access

Prognostic Value of Cystatin C Across Ejection Fraction Spectrum in Heart Failure With Normal to Mild Renal Dysfunction Original Investigation

Key Points

The study aims to evaluate the predictive value of cystatin C for adverse outcomes in heart failure patients with normal to mild renal dysfunction across different ejection fractions.
Single-center cohort study with 637 heart failure patients categorized by ejection fraction.
Used Cox regression models to assess relationships between cystatin C levels and risks of mortality and rehospitalization.
Evaluated the prognostic value of cystatin C using C-index, IDI, and NRI.
With 9.4 years of follow-up, 271 patients died and 330 were rehospitalized for heart failure.
Elevated cystatin C levels significantly increased risks of all-cause mortality (HR = 1.99) and rehospitalization (HR = 1.95).
Cystatin C demonstrated less prognostic impact on mortality in preserved ejection fraction patients compared to reduced and mid-range ejection fraction groups.

Abstract

ABSTRACT Background Cystatin C (CysC)'s predictive utility for long‐term adverse outcomes in heart failure (HF) patients with normal to mild renal insufficiency remains unclear. This study investigates the relationship between CysC and adverse outcomes in HF patients across the whole ejection fraction (EF) spectrum with normal to mild renal insufficiency. Methods In this single‐center cohort study, 637 HF patients with normal to mild renal insufficiency were categorized into reduced EF (HFrEF), mid‐range EF (HFmrEF), and preserved EF (HFpEF) groups. Associations between natural log unit (CysC) and risks of all‐cause mortality and HF rehospitalization were examined using Cox regression models. C‐index, IDI, and NRI assessed the incremental prognostic value. Results Over a follow‐up of 9.4 years, 271 patients died, and 330 were rehospitalized for HF. Multivariate Cox regression analysis indicated significant associations between elevated CysC levels and increased risks of all‐cause mortality (HR = 1.99, 95% CI: 1.57–2.54) and HF rehospitalization (HR = 1.95, 95% CI: 1.57–2.42) across all patients. HR's for all‐cause mortality observed for HFmrEF (HR 4.73, 95% CI: 2.08−10.74) and HFrEF (HR 15.11, 95% CI: 6.24−36.60) were higher compared to those for HFpEF patients (HR = 1.48, 95% CI 0.98−2.23), and CysC showed less prognostic impact on all‐cause mortality in HFpEF patients. Including CysC in the MAGGIC risk score‐based model provided additional prognostic value for all subjects, even with N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels added. Conclusions CysC is an independent risk factor for adverse outcomes in HF patients across EF spectrum with normal to mild renal insufficiency. Integrating CysC into the MAGGIC risk score‐based model enhances its prognostic capability for predicting adverse outcomes in the general HF population. Its prognostic effect on all‐cause mortality is limited in HFpEF patients.

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