Journal Article

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

Hao, Benchuan, Lyu, Lyu, Xu, Juan, Yang, Qiang, Wei, Yun, Liu, Hongbin

2026

Overview

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. Methods and cohort: HF patients with normal to mild renal insufficiency (n = 637), divided into HFpEF, HFmrEF, and HFrEF. Statistical Method: Cox regression models, Kaplan‐Meier Curves, C‐index, IDI, and NRI. Findings: Over a follow‐up of 9.4 years, significant associations of elevated CysC levels with increased risks of all‐cause mortality and HF rehospitalization across all patients were found. Including CysC in the MAGGIC risk score‐based model provided additional prognostic value for patients with normal to mild renal insufficiency. In subgroup analysis, comparable results were observed in HFmrEF and HFrEF patients. However, CysC showed less prognostic impact on all‐cause mortality in HFpEF patients (HR = 1.48, 95% CI: 0.98−2.23). Conclusions: CysC is an independent risk factor for adverse outcomes in HF patients across the EF spectrum with normal to moderate renal insufficiency. Integrating CysC into the MAGGIC risk score‐based model enhances its prognostic capability for predicting adverse outcomes in the general HF population, although its prognostic effect on all‐cause mortality is limited in HFpEF patients. Summary Our research is the first to demonstrate a significant correlation between Cystatin C levels and long‐term outcomes across all hospitalized heart failure patient types with normal to mildly impaired renal function, backed by an extensive follow‐up period. It is also the first to reveal the incremental prognostic benefit of adding Cystatin C to the MAGGIC risk score‐based model for all HF patient groups. Cystatin C proves to be a valuable biomarker for predicting the risk of adverse outcomes in heart failure patients with normal to mildly impaired renal function and coronary heart disease, based on a median follow‐up period of 9.4 years. However, in patients with heart failure with preserved ejection fraction, Cystatin C showed a reduced predictive value for all‐cause mortality. Incorporating Cystatin C into the MAGGIC risk score‐based model enhances its prognostic value for predicting adverse outcomes.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: ACE inhibitors / Aged / Angioplasty / Biomarkers - blood / Blood pressure / Body mass index / Cardiac arrhythmia / Cardiology / Cardiovascular disease / Cause of Death - trends / Chronic obstructive pulmonary disease / Clinical / Coronary vessels / cystatin C / Cystatin C - blood / Diabetes / Ejection fraction / Enzymes / Female / Follow-Up Studies / Glomerular Filtration Rate / Heart attacks / Heart Failure - blood / Heart Failure - complications / Heart Failure - diagnosis / Heart Failure - mortality / Heart Failure - physiopathology / heart failure with mid‐range ejection fraction / heart failure with preserved ejection fraction / heart failure with reduced ejection fraction / Heart rate / Heart surgery / Hemoglobin / Hospitals / Humans / Hypertension / Kidney diseases / Lipoproteins / Male / Middle Aged / Patient Readmission / Peptides / Predictive Value of Tests / Prognosis / Pulmonary arteries / Renal Insufficiency - blood / Renal Insufficiency - physiopathology / Retrospective Studies / Risk Assessment / Risk Factors / Stroke Volume - physiology / the Meta‐Analysis Global Group in Chronic Heart Failure Risk Score / Time Factors / Triglycerides / Variables / Veins & arteries / Ventricular Function, Left - physiology