Abstract
The authors investigated the time-dependent action of atorvastatin and simvastatin on oxidative stress and cytokine levels immediately after the start of treatment. These factors play a role in endothelial dysfunction. Hyperlipidemic patients (n=132) were assigned to treatment with 40 mg atorvastatin, 40 mg simvastatin, or placebo. Blood samples were taken before, 2 hours, 24 hours, 7 days, and 3 weeks after the administration of the statin or placebo to evaluate serum concentrations of total peroxides (TP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and soluble intercellular vascular adhesion molecule 1 (sICAM 1). In the atorvastatin group the TP changes were significantly different at 2 hours and 24 hours (p=0.005), whereas in the simvastatin group there was a gradual, more or less linear decline in TP until 7 days (p=0.006) and then a plateau. Simvastatin exhibited a faster statistically significant decrease over time in IL-6 and sICAM 1 levels (at 7 days, p=0.014 and p=0.001, respectively). TNF-a demonstrated a faster linear trend in the simvastatin group, but the significant effect appeared late (p=0.006). Both simvastatin and atorvastatin exerted early beneficial effects on oxidative stress, proinflammatory cytokines, and endothelial activation in hyperlipidemic subjects. These effects became significant 2 hours following the initiation of therapy.
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