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The Fibrosis Marker Syndecan-1 and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction
Study Questions:
What is the role of syndecan-1 (a mediator of cell-matrix interactions) in heart failure (HF)?
Methods:
The study investigators measured plasma syndecan-1 levels in 567 chronic HF patients. The primary endpoint was a composite of all-cause mortality and re-hospitalization for HF at 18 months.
Results:
The mean age of the study cohort was 71.0 ± 11.0 years, 38% were women, mean left ventricular ejection fraction (LVEF) was 32.5 ± 14.0%, and median syndecan-1 levels were 20.1 ng/ml (interquartile range, 13.9-27.7 ng/ml). Higher syndecan-1 levels occurred in HF patients who were more often male, and had higher NT-proBNP levels and worse renal function. Using multivariable regression analyses, the study investigators found a correlation between syndecan-1 levels and markers of fibrosis and remodeling, but no correlation with markers of inflammation. Using interaction analysis, they found an interaction between LVEF and syndecan-1 (p = increased risk of the primary outcome in diastolic HF patients [hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; p = 0.017), but not in systolic HF patients (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; p = 0.729). When added to a prediction model with established risk factors, syndecan-1 enhanced risk classification in diastolic HF.
Conclusions:
The authors concluded that in HF, syndecan-1 levels correlate with fibrosis biomarkers, suggesting a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in diastolic HF, but not in systolic HF patients.
Perspective:
This is an important study because it suggests that syndecan-1 may play a central role in the pathogenesis of HF. Its importance is probably due to the fact that it plays an important part in the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases. This study should prompt prospective clinical trials to better determine its role in the remodeling accompanying HF.
Keywords: Syndecan-1, Heart Failure, Diastolic, Matrix Metalloproteinases, Peptide Fragments, Stroke Volume, Natriuretic Peptide, Brain
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