Soluble Fas: a novel predictor of atherosclerosis in dialysis patients¹ ☆

Abstract 

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.

Keywords:  Cardiovascular disease (CVD), atherosclerosis, dialysis, apoptosis, soluble Fas (sFas), inflammation

• 1 Published in abstract form in J Am Soc Nephrol 12:416A, 2001.