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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:168.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Increased Soluble Fas Plasma Levels in Subjects at High Cardiovascular Risk

Atorvastatin on Inflammatory Markers (AIM) Study, a Substudy of ACTFAST

Luis M. Blanco-Colio; Jose L. Martín-Ventura; Eduardo de Teresa; Csaba Farsang; Allan Gaw; GianFranco Gensini; Lawrence A. Leiter; Anatoly Langer; Pierre Martineau; Gonzalo Hérnandez; Jesús Egido on behalf of the ACTFAST investigators

From the Vascular Research Lab (L.M.B.-C., J.L.M.-V.), Fundación Jimenéz Díaz, Autonoma University, Madrid, Spain; University of Malaga & V. de la Victoria Hospital (E.d.T.), Malaga, Spain; 1^st Department Med. Semmelweis University (C.F.), Budapest, Hungary; University of Glasgow (A.G.), Glasgow, UK; University of Florence, Careggi Hospital (G.G.), Firenze, Italy; University of Toronto & St-Michael’s Hospital (L.A.L., A.L.), Toronto, ON, Canada; Canadian Heart Research Centre (A.L.), Toronto, ON, Canada; Medical Division, Pfizer Canada (P.M.), Kirkland, QC, Canada; and R&D Department, Medical Division, Pfizer Spain (G.H.), Madrid, Spain.

Correspondence to Professor Jesús Egido, MD, PhD, Vascular Research Laboratory, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain. E-mail jegido{at}fjd.es

Objectives— 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.

Methods and 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 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.

1078 statin-free subjects with coronary heart disease (CHD), CHD-equivalent, or a 10-year CHD risk>20% were assigned to atorvastatin (10 to 80 mg/day) based on LDL-C at screening. At baseline, sFas concentrations are increased whereas sFasL are decreased compared with healthy subjects. Atorvastatin reduces sFas supporting the antiinflammatory effects in high-cardiovascular risk patients.

Key Words: inflammation • atorvastatin • soluble Fas • C-reactive protein • statins

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