title: Increased soluble Fas plasma levels in subjects at high cardiovascular risk: Atorvastatin on Inflammatory Markers (AIM) study, a substudy of ACTFAST.
abstract: OBJECTIVE
  Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment.
  
  
  RESULTS
  ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk > 20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides < or = 600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL.
  
  
  CONCLUSIONS
  sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.
authors.affiliation: Vascular Research Laboratory, Fundación Jiménez Díaz, Autonoma University, Avenida Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Blanco-Colio
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martín-Ventura
authors.forename: Eduardo
authors.initials: E
authors.lastname: de Teresa
authors.forename: Csaba
authors.initials: C
authors.lastname: Farsang
authors.forename: Allan
authors.initials: A
authors.lastname: Gaw
authors.forename: GianFranco
authors.initials: G
authors.lastname: Gensini
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.forename: Anatoly
authors.initials: A
authors.lastname: Langer
authors.forename: Pierre
authors.initials: P
authors.lastname: Martineau
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Hérnandez
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D003920:Diabetes Mellitus / Q000097:blood; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000097:blood* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors; D019014:fas Receptor / Q000097:blood* / Q000235:genetics
chemical_list: D000924:Anticholesteremic Agents; C491901:FAS protein, human; D053222:Fas Ligand Protein; D006538:Heptanoic Acids; D011758:Pyrroles; D019014:fas Receptor; D002097:C-Reactive Protein; D000069059:Atorvastatin