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Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction

Tromp, Jasper
van der Pol, Atze
Klip, IJsbrand
de Boer, Rudolf
Jaarsma, Tiny
van Gilst, Wiek
Voors, Adriaan
van Veldhuisen, Dirk
van der Meer, Peter
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Abstract
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 (HF). Methods and Results: We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0±11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5±14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9–27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide 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 left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14–3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71–1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions: In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
Keywords
Date
2014
Type
Journal article
Journal
Circulation: Heart Failure
Book
Volume
7
Issue
3
Page Range
457-462
Article Number
ACU Department
Faculty of Health Sciences
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Source URL
Event URL
Open Access Status
Open access
License
File Access
Controlled
Notes