Abstract 4195: High-Dose Atorvastatin Therapy Can Completely Reverse Monocyte Dysfunction in Hypercholesterolemic Patients with Coronary Artery Disease
Statins, a key component in the primary and secondary CAD prevention, reduce cardiovascular events even in normo- and hypocholesterolemic individuals. Intact monocyte function is crucial for collateral artery development. In the presence of hypercholesterolemia (HC), collateral formation is severely impaired. We could previously show that MCP-1-induced monocyte chemotaxis is significantly decreased in hypercholesterolemic CAD patients. Therefore, we investigated whether a therapy with atorvastatin 40 mg once a day could improve monocyte function in CAD patients with HC, and whether this influences MCP-1 plasma levels. Fifty CAD patients with HC as a single cardiovascular risk factor were randomized to receive either atorvastatin 40 mg or a placebo once daily for 4 weeks. Monocytes were isolated from peripheral blood. Their migratory responsiveness towards MCP-1 (10 ng/ml) was assessed in a micro-chemotaxis chamber before and at the end of the study. MCP-1 plasma levels were analyzed using ELISA. Before starting study medication, monocyte chemotaxis towards MCP-1 did not differ between the atorvastatin group and the placebo group (122% vs. 114%; p=NS). After 4 weeks, the migratory response of monocytes from atorvastatin-treated patients significantly improved, whereas the monocytes from placebo-treated patients showed a further decline in function (149% vs. 109%; p<0.001). A significant negative correlation existed between LDL-C levels and MCP-1-induced monocyte chemotaxis (p<0.001). With regard to MCP-1 plasma levels, there was no significant difference in CAD patients treated with or without atorvastatin (476 vs. 671 pg/ml; p=NS) for 4 weeks.Based on our data, a high-dose atorvastatin therapy can completely reverse the negative influence of HC on monocyte function, whereas monocyte chemotaxis further decreases in the absence of any lipid-lowering therapy. The migratory responsiveness of monocytes is closely associated with LDL-levels indicating that statin effects on monocytes are rather cholesterol-dependent than pleiotropic. High-dose statin therapy might be regarded as an important contribution to primary and secondary prevention in CAD by improving the patients’ ability to form functional coronary collaterals.