Soluble Fas: a novel predictor of atherosclerosis in dialysis patients.
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).


CONCLUSIONS
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.
Division of Nephrology, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Canada.
Stéphan
S
Troyanov
Marie-Josée
MJ
Hébert
Mélanie
M
Masse
Normand
N
Vigneault
Isabelle
I
Sirois
François
F
Madore
D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D012307:Risk Factors; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D019014:fas Receptor