title: Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects.
abstract: OBJECTIVE
  Recent studies suggest an association between acute inflammation and deterioration of arterial function. The effect of acute inflammation on endothelial function and the role of treatment with statins have not been investigated in subjects with dyslipidaemia.
  
  
  RESULTS
  In this randomized, placebo-controlled, double-blind study, we generated a transient systemic inflammation by Salmonella typhi vaccination in 50 volunteers with mild hypercholesterolaemia after 4 days of treatment with atorvastatin 40 mg or placebo once daily. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery and circulating levels of endothelial and inflammatory markers were measured before and 8 h after the vaccine. Vaccination produced a decline on FMD at 8 h (absolute decrease of 2.55%, P = 0.001), indicating an unfavourable effect on endothelial function. In contrast, in atorvastatin-treated subjects, FMD was preserved after vaccination (decrease of 0.15%, P = 0.005 vs. placebo). The vaccination-induced decline in plasma level of nitric oxide metabolites (by 6.0 micromol/L, P = 0.007) and antioxidant capacity (by 20.6 micromol/L, P = 0.001) in the placebo group were completely abolished by atorvastatin (P = 0.038 and P = 0.005, respectively, vs. placebo). In contrast, atorvastatin had no significant effect on cytokine levels.
  
  
  CONCLUSIONS
  Acute inflammation is aetiologically associated with the deterioration of vasomotor and systemic endothelial function in hypercholesterolaemic patients. Atorvastatin effectively abrogates these deleterious effects.
authors.affiliation: Peripheral Vessels and Hypertension Units, First Department of Cardiology, Athens Medical School, Hippokration Hospital, Vas. Sofias avenue 114, Athens 11528, Greece. cvlachop@otenet.gr
authors.forename: Charalambos
authors.initials: C
authors.lastname: Vlachopoulos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Aznaouridis
authors.forename: Anna
authors.initials: A
authors.lastname: Dagre
authors.forename: Carmen
authors.initials: C
authors.lastname: Vasiliadou
authors.forename: Constantina
authors.initials: C
authors.lastname: Masoura
authors.forename: Elli
authors.initials: E
authors.lastname: Stefanadi
authors.forename: John
authors.initials: J
authors.lastname: Skoumas
authors.forename: Christos
authors.initials: C
authors.lastname: Pitsavos
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D001916:Brachial Artery; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011758:Pyrroles / Q000627:therapeutic use*; D022562:Salmonella Vaccines / Q000494:pharmacology; D012485:Salmonella typhi; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy*; D014652:Vascular Diseases / Q000188:drug therapy*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D022562:Salmonella Vaccines; D000069059:Atorvastatin