Tromp, J., van der Pol, A., Klip, I., de Boer, R., Jaarsma, T., van Gilst, W., Voors, A., van Veldhuisen, D. & van der Meer, P. (2014). Fibrosis marker syndecan-1 and outcome in patients with heart failure with reduced and preserved ejection fraction. Circulation: Heart Failure,7(3), 457-462. Retrieved from https://doi.org/10.1161/CIRCHEARTFAILURE.113.000846
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.
Mary MacKillop Institute for Health Research
Open Access Journal Article