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Soluble Fas: a novel predictor of atherosclerosis in dialysis patients
Stéphan Troyanov1, Marie-Josée Hébert, Mélanie Masse
1Division of Nephrology, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Canada.
Insights
Elevated soluble Fas (sFas) levels predict cardiovascular disease (CVD) events in hemodialysis patients. This finding suggests sFas is an independent predictor of atherosclerosis in end-stage renal disease (ESRD).
Area of Science:
- Nephrology
- Cardiology
- Immunology
Background:
- Cardiovascular disease (CVD) is the primary cause of mortality in end-stage renal disease (ESRD) patients.
- The Fas/Fas-ligand (Fas-L) system and apoptosis dysregulation are implicated in atherosclerosis development.
- Previous studies suggest a link between soluble Fas (sFas) and CVD, but its predictive value for future events is unclear.
Purpose of the Study:
- To investigate the role of plasma soluble Fas (sFas) and soluble Fas-ligand (sFas-L) levels in predicting cardiovascular events.
- To determine if sFas and sFas-L are independent predictors of CVD in chronic hemodialysis patients.
Main Methods:
- Prospective cohort study of 107 chronic hemodialysis patients.
- Measurement of baseline plasma sFas and sFas-L levels.
- Follow-up for cardiovascular events over 27 months, analyzed using Cox proportional hazards models.
Main Results:
- A significant association was found between higher baseline sFas levels and increased risk of cardiovascular events (P = 0.03).
- sFas-L levels were not significantly associated with cardiovascular events.
- Increased sFas levels predicted CVD events independently of traditional risk factors and inflammation markers like C-reactive protein (CRP).
- Higher CRP levels were also associated with cardiovascular events (P = 0.04).
- Cardiovascular mortality was significantly higher in patients with the highest sFas tertile compared to the lowest (27.8% vs 8.6%; P = 0.04).
Conclusions:
- Elevated plasma sFas levels are a significant predictor of future cardiovascular disease in ESRD patients.
- sFas represents a novel and independent biomarker for active atherosclerotic disease in this population.
Background:
Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Disregulation of apoptosis within the vessel wall and upregulation of the Fas/Fas-ligand (Fas-L) system contribute to the development of atherosclerosis. Cross-sectional studies have suggested that elevated plasma levels of the soluble form of Fas (sFas) are associated with CVD. However, the role of sFas and sFas-L in predicting future cardiovascular events has yet to be defined.
Methods:
We evaluated the role of plasma sFas and sFas-L levels as predictors of CVD in a prospective cohort of 107 chronic hemodialysis patients.
Results:
During the study period (27 months), 53 patients (49.5%) presented with at least one cardiovascular end point. On univariate analysis, baseline sFas levels were significantly associated with the occurrence of cardiovascular end points, whereas sFas-L levels were not. Using Cox proportional hazards, increased sFas levels were associated with a significantly greater risk for cardiovascular end points (P = 0.03). This effect was independent of baseline CVD history, classic risk factors for atherosclerosis (diabetes, hypercholesterolemia, hypertension, and smoking), and markers of inflammation (C-reactive protein [CRP], soluble intercellular adhesion molecule-1). Increased CRP levels also were associated with cardiovascular end points (P = 0.04). In addition, increased cardiovascular mortality was found in patients in the highest sFas tertile compared with those in the lowest tertile (27.8% versus 8.6%; P = 0.04).
Conclusion:
Increased plasma sFas levels are predictive of future CVD. These results suggest that sFas is a novel and independent predictor of active atherosclerotic disease in patients with ESRD.
