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

Abstract

Background and purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.