Introduction
Endothelial glycocalyx (eGC) contains proteoglycan polymers, such as syndecan-1, heparan
sulfate (HS), and hyaluronic acid (HA), which play an important role in protecting
endothelial cells from inflammatory cells and cytokines, as well as regulating intravascular
volume. Disruption of eGC has been shown to be associated with heart failure (HF),
but the prognostic role of serum syndecan-1, heparan sulfate, and hyaluronic acid
remain to be elucidated.
Hypothesis
Increased serum syndecan-1, HS, and HA may be associated with decreased survival in
patients with HF with reduced ejection fraction (HFrEF).
Methods
Healthy controls, HFrEF patients presented with acute decompensated HF (ADHF), and
chronic HF (CHF) were recruited from three separate ongoing cohorts at the Cleveland
Clinic. Whole blood was collected from each subject at the day of enrollment. Primary
endpoint is accumulated survival.
Results
51 healthy controls and 138 patients with HFrEF (66 ADHF patients and 72 CHF patients)
were prospectively enrolled. During the follow-up time of 557±363 days, 12 (18.2%)
ADHF and 9 (12.5%) CHF patients died. Serum syndecan was significantly elevated in
ADHF compared to patients with CHF and healthy controls (101.4±77.3 vs 53.5±65.6 and
35.7±54.2 ng/mL, respectively, p =0.001), as well as serum HS (9806±23943, 4075±4243, and 2182±1187 ng/mL, respectively,
p =0.011), and HA (75.9±76.2, 49.4±50.8, and 37.3±27.4 ng/mL, respectively, p = 0.001). In HF patients, serum elevated serum syndecan-1 and HS (above median, 43.56
and 3384.5 ng/mL, respectively) were associated with decreased accumulated survival
(log rank p = 0.007, and 0.016, respectively) (Figure). However, elevated serum HA was not associated
with survival (log rank p = 0.257). In multivariate cox regression analysis adjusting for gender, BMI, and
systolic blood pressure, only heparan sulfate was independently associate with all-cause
mortality (hazard ratio per doubling 1.315, 95% confidence interval 1.012-1.709, p = 0.040).
Conclusions
Serum eGC was substantially increased in patients with ADHF, and elevated serum syndecan-1
and HS were associated with decreased survival in patients with HFrEF.
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Copyright
© 2020 Published by Elsevier Inc.
