title: Statin treatment is not associated with consistent alterations in inflammatory status of carotid atherosclerotic plaques: a retrospective study in 378 patients undergoing carotid endarterectomy.
abstract: OBJECTIVE
  Anti-inflammatory qualities are held partially responsible for the reduction of cardiovascular events after statin treatment. We examined the phenotype of carotid atherosclerotic plaques harvested during carotid endarterectomy in relation to the previous use of different statins prescribed in clinical practice.
  
  
  METHODS
  Three hundred and seventy-eight patients were included. Atherosclerotic plaques were harvested, immunohistochemically stained and semiquantitively examined for the presence of macrophages (CD68), smooth muscle cells, collagen and fat. Adjacent atherosclerotic plaques were used to study protease activity and interleukin levels. Patients' demographics were recorded and blood samples were stored.
  
  
  RESULTS
  Serum cholesterol, low-density lipoprotein, apolipoprotein B, and C-reactive protein levels were lower in patients treated with statins compared with patients without statin treatment. Atheromatous plaques were less prevalent in patients receiving statins compared with patients without statin therapy (29% versus 42%, P=0.04). An increase of CD68 positive cells was observed in patients receiving statins compared with nonstatin treatment (P=0.05). This effect was specifically related to atorvastatin treatment. In patients treated with atorvastatin, the increased amount of CD68 positive cells were not associated with increased protease activity. In contrast, a dose-dependent decrease in protease activity was shown in the atorvastatin group. Interleukin 6 expression was lower in plaques obtained from patients treated with statins (P=0.04).
  
  
  CONCLUSIONS
  Statin use may exert pleiotropic effects on plaque phenotype. However, not the presence of macrophages but activation with subsequent protease and cytokine release may be attenuated by statin use.
authors.affiliation: Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Bart A N
authors.initials: BA
authors.lastname: Verhoeven
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Johan A F
authors.initials: JA
authors.lastname: Koekkoek
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Jean Paul P M
authors.initials: JP
authors.lastname: de Vries
authors.forename: Jan H
authors.initials: JH
authors.lastname: Verheijen
authors.forename: Evelyn
authors.initials: E
authors.lastname: Velema
authors.forename: Els
authors.initials: E
authors.lastname: Busser
authors.forename: Arjan
authors.initials: A
authors.lastname: Schoneveld
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016207:Cytokines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D016894:Endarterectomy, Carotid; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D019821:Simvastatin / Q000627:therapeutic use; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000069059:Atorvastatin; D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010447:Peptide Hydrolases; D017035:Pravastatin; D011758:Pyrroles; D019821:Simvastatin; C067980:CD68 antigen, human; D000097382:CD68 Molecule