title: Upregulation of the immune system in primary hypercholesterolaemia: effect of atorvastatin therapy.
abstract: OBJECTIVE
  High levels of plasma high sensitivity C-reactive protein (CRP), sensitive to therapy with statins, have been described in hypercholesterolaemia. In vitro evidence shows that CRP activates the complement system, which, in turn, leads to an increased expression of ICAM-1. Our objectives were to verify whether primary hypercholesterolaemia (PHC) is associated with an upregulation of the inflammatory/immune response, and whether this is sensitive to atorvastatin.
  
  
  RESULTS
  We examined the levels of sICAM-1, C3, C4 complement fractions in 48 patients with PHC, with (CAD group) or without (No-CAD group) coronary artery disease (CAD) in comparison with a group of 48 healthy controls. The two patient groups were studied before and after atorvastatin therapy. Both hypercholesterolaemic groups showed higher mean values of sICAM-1, C3 and C4 (P < 0.0001) when compared with the controls. The two groups of patients responded differently to atorvastatin therapy. After 3 months, the C3 levels normalized in both groups of patients (P < 0.02 compared with basal values); C4 was greatly reduced only in the CAD group (P < 0.01). After 12 months of therapy, in CAD group C3 mean levels were still significantly lower than baseline values (P < 0.01); a further decrease in the C4 values (P < 0.05 with respect to levels after 3 months of therapy) and also a substantial reduction in sICAM-1 values (P < 0.001 with respect to basal values) were observed.
  
  
  CONCLUSIONS
  High plasma values of C3 and C4 in PHC cluster with high values of sICAM-1, distinguish subjects with CAD and could be used to monitor the anti-inflammatory effect of statin therapy in these patients.
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy. tizisamp@ifc.cnr.it
authors.forename: T
authors.initials: T
authors.lastname: Sampietro
authors.forename: F
authors.initials: F
authors.lastname: Bigazzi
authors.forename: G
authors.initials: G
authors.lastname: Rossi
authors.forename: B
authors.initials: B
authors.lastname: Dal Pino
authors.forename: M R
authors.initials: MR
authors.lastname: Puntoni
authors.forename: F
authors.initials: F
authors.lastname: Sbrana
authors.forename: E
authors.initials: E
authors.lastname: Chella
authors.forename: A
authors.initials: A
authors.lastname: Bionda
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000276:immunology; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; D000069059:Atorvastatin