The Fibrosis Marker Syndecan-1 and Outcome in Heart Failure Patients with Reduced and Preserved Ejection Fraction
Background—Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure.
Methods and Results—We analyzed plasma syndecan-1 levels in 567 chronic heart failure patients. Primary endpoint was a composite of all-cause mortality and re-hospitalization for heart failure at 18 months. Mean age was 71.0±11.0 years, 38% was female, and mean LVEF was 32.5±14.0%. Median syndecan-1 levels were 20.1 ng/mL (IQR 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often male, had higher NT-proBNP levels and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling, but no correlation with inflammation markers. Interaction analysis revealed an interaction between LVEF and syndecan-1 (p=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in HFpEF patients (hazard ratio 2.10, 95%confidence interval 1.14-3.86; p=0.017) but not in HFrEF patients (hazard ratio 0.95, 95%confidence interval 0.71-1.27; p=0.729). Finally, syndecan-1 enhanced risk classification in HFpEF patients when added to a prediction model with established risk factors.
Conclusions—In patients with heart failure, syndecan-1 levels correlate with fibrosis biomarkers pointing towards a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in HFpEF, but not in HFrEF patients.
- Received September 19, 2013.
- Accepted March 11, 2014.