title: Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration.
abstract: BACKGROUND
  Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1) and monocyte chemoattractant protein 1 (sMCP-1) are associated with increased risk for future coronary events. However, the effect of statins on these inflammatory markers has hardly been studied. We analyzed whether treatment with the different doses of atorvastatin affects sICAM-1 and sMCP-1 plasma levels in subjects at high cardiovascular risk.
  
  
  METHODS
  Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration was a 12-week, prospective, multicenter, open-label trial that enrolled a total of 2117 subjects with coronary heart disease (CHD), CHD equivalent (defined as diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects with low-density-lipoprotein cholesterol between 100 and 220 mg/dL (2.6-5.7 mmol/L) and triglycerides <600 mg/dL (6.8 mmol/L) were assigned to atorvastatin (10-80 mg/d) based on low-density-lipoprotein cholesterol at screening. The Atorvastatin on Inflammatory Markers study included statin-free patients (N = 1078).
  
  
  RESULTS
  At baseline, 52%, 14%, 12%, and 22% of subjects were assigned to doses of 10, 20, 40, and 80 mg, respectively. Levels of sICAM-1 [geometric mean (95% confidence interval); 283.8 (278.1-289.6) vs 131.9 (127.2-136.6) ng/mL, P < .0001] and sMCP-1 [164.1 (159.9-168.2) vs 131.1 (123.1-139.6 pg/mL, P < .0001] were increased in subjects at high cardiovascular risk compared to healthy subjects (n = 130). In the whole population, sICAM-1 and sMCP-1 levels were reduced by atorvastatin [% change (95% confidence interval); -2.2 (-3.8 to -0.6); -4.1 (-6.1 to -2); P = .006 and P = .0002, respectively]. All doses of atorvastatin diminished sICAM-1 and sMCP-1 levels in the highest quartile.
  
  
  CONCLUSIONS
  Short treatment with atorvastatin reduced sICAM-1 and sMCP-1 plasma levels showing anti-inflammatory effects in subjects at high cardiovascular risk.
authors: Vascular Research Laboratory, Fundación Jimenéz Díaz, Autonoma University, Madrid, Spain.
authors: Luis Miguel
authors: LM
authors: Blanco-Colio
authors: Jose Luis
authors: JL
authors: Martín-Ventura
authors: Eduardo
authors: E
authors: de Teresa
authors: Csaba
authors: C
authors: Farsang
authors: Allan
authors: A
authors: Gaw
authors: GianFranco
authors: G
authors: Gensini
authors: Lawrence A
authors: LA
authors: Leiter
authors: Anatoly
authors: A
authors: Langer
authors: Pierre
authors: P
authors: Martineau
authors: Jesús
authors: J
authors: Egido
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D048909:Diabetes Complications / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol; D000069059:Atorvastatin