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

摘要

Background: Interleukin‐18 (IL‐18), a novel proinflammatory marker, and matrix metalloproteinaolemia. 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.