Intensive treatment with atorvastatin reduces inflammation in mononuclear cells and human atherosclerotic lesions in one month

Background and Purpose - To investigate the effect of short-term high-dose atorvastatin on blood and plaque inflammation in patients with carotid stenosis. Methods - Twenty patients undergoing carotid endarterectomy without previous statin treatment were randomized to receive either atorvastatin 80 mg/d (n = 11) or no statins (n = 9) for 1 month. We studied inflammatory mediators in plasma (enzyme-linked immunosorbent assay), peripheral blood mononuclear cells (PBMCs; quantitative RT-PCR and EMSA) and plaques (immunohistochemistry and Southwestern histochemistry). Results -Atorvastatin significantly decreased total and low-density lipoprotein cholesterol and prostaglandin E₂ plasma levels. PBMCs from treated patients showed impaired NF-κB, activation and MCP-1 and COX-2 mRNA expression. Carotid atherosclerotic plaques demonstrated a significant reduction in macrophage infiltration, activated NF-κB, and COX-2 and MCP-1 expression. Conclusions - Intensive treatment with atorvastatin decreases inflammatory activity of PBMCs and carotid atherosclerotic plaques in I month. These data strongly suggest that the antiinflammatory effect of high doses of statins in humans can be seen very early.