Syndecan-1 in Acute Decompensated Heart Failure　– Association With Renal Function and Mortality –

Abstract

Background: Heart failure (HF) is a leading cause of hospitalization throughout the world, and the mortality rate remains elevated. HF is frequently complicated by acute kidney injury (AKI), worsening the patient's prognosis. There have been no studies evaluating the role that endothelial glycocalyx damage plays in HF patients and its association with AKI and mortality. Methods and Results:We measured several endothelial biomarkers in 201 consecutive patients with acute decompensated HF (ADHF) during emergency department (ED) admission. In-hospital mortality, AKI development and 6-month mortality rates were assessed. ADHF patients with worsening renal function had higher levels of syndecan-1 but not those patients with stable chronic kidney disease. Syndecan-1 levels during ED admission were predictive for AKI during the hospital stay (AUC 0.741, P<0.001) and had an even better discriminatory capacity in more severe AKI (AUC 0.812, P<0.001). Additionally, after adjusting for several confounding factors, including biomarkers of endothelial function and endothelial cell activation, syndecan-1 remained associated with in-hospital mortality rates. On a Cox multivariate analysis regression, syndecan-1 was associated with 6-month mortality rates. Conclusions:The concentration of syndecan-1, a marker of glycocalyx damage measured during ED admission, is valuable in assessing the risk of developing AKI and in-hospital mortality. Its association with mortality is strong after 6-month follow-up. mellitus, arterial hypertension, chronic pulmonary obstructive disease and drug prescription history. During the hospital stay, patients were evaluated daily and the laboratory data were collected. The length of hospital stay (LOS) and in-hospital mortality rates were recorded. After being discharged from the hospital, patients were followed up for 6 months to assess late mortality rates. The Institutional Ethical Committee approved all the procedures in this study.

The glycocalyx and its significance in human medicine

“…The authors suggested that TNF-a-induced MMP9-mediated shedding of syndecan-4 is likely to contribute to EC GCX disruption observed in diabetes and inflammatory states. Neves et al [63] evaluated the relationship between plasma syndecan-1 levels and renal dysfunction or mortality in patients with acute decompensated heart failure. They determined that plasma syndecan-1 levels predicted increased risk of developing acute kidney injury, in-hospital death and mortality during the 6-month follow-up, suggesting that plasma syndecan-1 may be a useful biomarker.…”

Endothelial Glycocalyx as Biomarker for Cardiovascular Diseases: Mechanistic and Clinical Implications

“…Neves et al studied 201 patients with acute decompensated heart failure [46]. The ratio of patients with sdc1 >125 ng/ml and <125 ng/ml was about 1:3, and the risk of 6 month-mortality was 22.4% and 8.5%, respectively.…”

“…The ratio of patients with sdc1 >125 ng/ml and <125 ng/ml was about 1:3, and the risk of 6 month-mortality was 22.4% and 8.5%, respectively. Higher serum soluble sdc1 was also associated with more frequent renal dysfunction during hospitalization [46]. …”

“…both studied 567 patients with acute heart failure, by measuring sdc1 following stabilization and prior to discharge [47, 48]. The ratio of patients with sdc1 >27.7 ng/mL and sdc1 < 27.6 ng/mL was about 1:4, suggesting a rapid decrease of serum soluble sdc1 levels when compared to the previous study [46]. Through univariable analysis, doubling of sdc1 significantly increased the risk of mortality (HR=1.2) in patients with preserved ejection fraction.…”

Endovascular shedding markers in patients with heart failure with reduced ejection fraction

“…Various conditions can lead to disruption of this endothelial barrier such as ischemia and hypoxia, oxidative stress and inflammation, hyperglycemia, volume and salt overload . It has already been demonstrated that a dysfunctional glycocalyx is involved in the process of atherosclerosis, endothelial dysfunction, tissue edema, renal dysfunction, and related to increased cardiovascular events in different patient populations . Therefore, there is growing interest to further study glycocalyx integrity.…”