Heparan Sulfate and Its Associations with Biochemical and Echocardiographic Parameters in Patients with Chronic Heart Failure Stratified by Cystatin C-Based Estimated Glomerular Filtration Rate.

Abstract

Background: Endothelial glycocalyx degradation may contribute to vascular dysfunction, systemic inflammation, and renal impairment in chronic heart failure (CHF). Heparan sulfate, a major component of the endothelial glycocalyx, is released into the circulation following glycocalyx injury.

Objective: To evaluate circulating heparan sulfate concentrations in patients with clinically stable CHF stratified by cystatin C-based estimated glomerular filtration rate (eGFR) and to examine their associations with renal, inflammatory, neurohormonal, and echocardiographic parameters.

Methods: This cross-sectional observational study included 100 patients with New York Heart Association functional class II–III CHF and 32 age- and sex-matched controls. Patients with CHF were stratified into Group I (eGFR 60–89 mL/min/1.73 m²; n = 50) and Group II (eGFR ≥90 mL/min/1.73 m²; n = 50). Serum heparan sulfate, cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations were measured. Echocardiographic parameters were assessed using standard methods. Associations were evaluated using Spearman’s rank correlation analysis, and the discriminatory performance of heparan sulfate was assessed using receiver operating characteristic curve analysis.

Results: Serum heparan sulfate concentrations were significantly higher in Group I than in Group II (236.2 ± 5.5 vs. 176.7 ± 1.5 ng/mL; P < 0.001) and the control group (63.1 ± 2.8 ng/mL; P < 0.001). Compared with Group II, Group I had higher cystatin C concentrations (1.05 ± 0.02 vs. 0.76 ± 0.01 mg/L; P < 0.001), lower cystatin C-based eGFR (72.9 ± 1.3 vs. 101.8 ± 1.3 mL/min/1.73 m²; P < 0.001), higher NT-proBNP concentrations (1256.5 ± 14.64 vs. 1027.4 ± 15.44 pg/mL; P < 0.001), higher IL-6 concentrations (9.9 ± 0.3 vs. 8.3 ± 0.4 pg/mL; P < 0.01), and a higher E/e′ ratio (15.2 ± 0.25 vs. 10.5 ± 0.21; P < 0.001). In Group I, heparan sulfate correlated positively with cystatin C (rₛ = 0.68), IL-6 (rₛ = 0.53), TNF-α (rₛ = 0.49), NT-proBNP (rₛ = 0.62), and E/e′ (rₛ = 0.52), and inversely with eGFR (rₛ = −0.64) and left ventricular ejection fraction (rₛ = −0.48; all P < 0.001). Similar but weaker associations were observed in Group II. Receiver operating characteristic analysis yielded an area under the curve of 0.968 (95% confidence interval, 0.934–1.000; P < 0.001). A heparan sulfate cutoff of ≥191.0 ng/mL distinguished mildly reduced from preserved eGFR with 88.0% sensitivity and 94.0% specificity.

Conclusion: Circulating heparan sulfate concentrations were elevated in patients with clinically stable CHF and were highest among those with mildly reduced cystatin C-based eGFR. Higher heparan sulfate concentrations were associated with poorer renal filtration, greater systemic inflammatory and neurohormonal activity, lower left ventricular systolic function, and higher estimated left ventricular filling pressure. These findings support the potential value of heparan sulfate as an integrative research biomarker of endothelial glycocalyx injury within the cardiorenal continuum; however, its clinical utility requires validation in larger multicenter studies.

Keywords:

chronic heart failure, heparan sulfate, endothelial glycocalyx, estimated glomerular filtration rate, renal dysfunction, cardiorenal syndrome

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