Effects of fluvastatin, an HMG-CoA reductase inhibitor, on serum levels of interleukin-18 and matrix metalloproteinase-9 in patients with hypercholesterolemia

Background: Interleukin-18 (IL-18), a novel proinflammatory marker, and matrix metalloproteinase-9 (MMP-9) represent the indices of plaque stability. It is unknown whether hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which provide anti-inflammatory and endothelium protection effects, have the property of stabilizing plaque in patients with hypercholesterolemia. Hypothesis: The study was designed to investigate the influence of statin therapy in circulating IL-18, MMP-9, and endothelial function. Methods: We investigated the effects of a 12-week therapy with fluvastatin on IL-18, MMP-9, and endothelial function in patients with hypercholesterolemia. Results: Compared with placebo, fluvastatin significantly improved flow-mediated vasodilatation to hyperemia, a hallmark of endothelial function [from 3.8% (-3.9 ∼ 15.2) to 5.9% (-0.3 ∼ 13.2), p = 0.001], and attenuated plasma levels of high sensitivity C-reactive protein (hsCRP) [from 1.3 (0.3 ∼ 7.7) to 1.1 mg/l (0.2 ∼ 3.5), p = 0.018], IL-18 [from 247.6 (145.4 ∼ 378.4) to 196.4 pg/dl (90.7 ∼ 380.2), p < 0.001], total MMP-9 (from 58 ± 46.3 to 39.4 ± 22.4 ng/dl, p = 0.023), and MMP-9 activity [from 6.4(3.6 ∼ 27) to 5.6 ng/dl (3.1 ∼ 13.7)]. However, no significant correlation was found between the degree of changes in lipid profile and flow-mediated dilatation (FMD) and plasma concentration of IL-18 and MMP-9. Conclusions: Fluvastatin reduced plasma concentrations of IL-18 and MMP-9, and improved endothelial function in patients with hypercholesterolemia independent of its lipid-lowering effect.