Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaernic subjects

Aims Recent studies suggest an association between acute inflammation and deterioration of arterial function. The effect of acute inflammation on endotheliat function and the rote of treatment with statins have not been investigated in subjects with dystipidaemia. Methods and results In this randomized, placebo-controlled, double-blind study, we generated a transient systemic inflammation by Salmonella typhi vaccination in 50 volunteers with mild hypercholesterotaemia 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 endotheliat 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 mu mol/L, P = 0.007) and antioxidant capacity (by 20.6 mu mol/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. Conclusion Acute inflammation is aetiologically associated with the deterioration of vasomotor and systemic endotheliat function in hypercholesterolaemic patients. Atorvastatin effectively abrogates these deleterious effects.