Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects.
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.
Vlachopoulos
Charalambos
C
Peripheral Vessels and Hypertension Units, First Department of Cardiology, Athens Medical School, Hippokration Hospital, Vas. Sofias avenue 114, Athens 11528, Greece. cvlachop@otenet.gr
Aznaouridis
Konstantinos
K
Dagre
Anna
A
Vasiliadou
Carmen
C
Masoura
Constantina
C
Stefanadi
Elli
E
Skoumas
John
J
Pitsavos
Christos
C
Stefanadis
Christodoulos
C
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
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D022562:Salmonella Vaccines; D000069059:Atorvastatin