Fluvastatin reduces oxidative stress, decreases serum monocyte chemotactic protein-1 level and improves endothelial function in patients with hypercholesterolemia.

Statins may have anti-inflammatory properties and exert endothelial protection independently of their lipid-lowering effect. However, data are scarce concerning the co-existence of these lipid-lowering-independent effects in humans.Forty three patients with hypercholesterolemia were randomly assigned in a 2:1 ratio to receive either fluvastatin 80 mg/day (n = 30) or placebo (n = 13) for 12 weeks. Plasma levels of monocyte chemotactic protein-1 (MCP-1), thiobarbituric acid reactive substances (TBARS)--an index of oxidative stress, and flow-mediated vasodilatation (FMD)--an index of endothelial function, were measured before and after statin therapy.Fluvastatin significantly reduced the serum level of total cholesterol (201.8 +/- 25.2 vs 271.6 +/- 24.7 mg/dL; p < 0.001), low-density lipoprotein cholesterol (129.4 +/- 5.1 vs 190.2 +/- 19 mg/dL; p < 0.001), MCP-1 (190.3 +/- 40 vs 217.6 +/- 61 pg/mL; p = 0.001), and TBARS (3.7 +/- 1.3 vs 5.2 +/- 1.4 nmol/mL; p < 0.001). FMD was significantly increased, from 3.7 +/- 2.5% to 5.9 +/- 2.9% (p < 0.001) in the fluvastatin group. The reduction of serum MCP-1 or TBARS level was not correlated with the improvement of either plasma cholesterol level or FMD. No significant changes of these markers were observed in the placebo group.Fluvastatin reduced oxidative stress and inflammatory marker levels, and improved endothelial function, in addition to its lipid-lowering effect. These observations provide a clinical rationale for the co-existence of complex and multiple vascular protective mechanisms of statins.