Intensive Treatment With Atorvastatin Reduces Inflammation in Mononuclear Cells and Human Atherosclerotic Lesions in One Month

Abstract

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-kappaB activation and MCP-1 and COX-2 mRNA expression. Carotid atherosclerotic plaques demonstrated a significant reduction in macrophage infiltration, activated NF-kappaB, and COX-2 and MCP-1 expression. CONCLUSIONS: Intensive treatment with atorvastatin decreases inflammatory activity of PBMCs and carotid atherosclerotic plaques in 1 month. These data strongly suggest that the antiinflammatory effect of high doses of statins in humans can be seen very early.