Comparative effects of diet and statin on NO bioactivity and matrix metalloproteinases in hypercholesterolemic patients with coronary artery disease

Objective-We investigated the effects of statin compared with the American Heart Association (AHA) Step I Diet on lipoproteins, vasomotor function, tumor necrosis factor (TNF)-alpha, and serological markers of plaque stability. Furthermore, we investigated the mechanism of regulation suggested by experimental studies. Methods and Results-For 14 weeks, we administered AHA diet+placebo and AHA diet+simvastatin (20 mg daily) to 31 and 32 randomly selected patients with coronary artery disease, respectively. Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia from 3.37 +/- 2.28% to 5.89 +/- 2.35% (P<0.001) and lowered plasma levels of C-reactive protein from 0.48 to 0.10 mg/dL (P<0.001), TNF-alpha from 3.38 to 2.79 pg/mL (P<0.001), total matrix metalloproteinase (MMP)-9 from 36 to 28 ng/mL (P=0.006), and tissue inhibitor of matrix metalloproteinase-1 from 80 +/- 30 to 74 +/- 23 ng/mL (P=0.041), and simvastatin lowered to a greater extent MMP-9 activity (from 71 to 52 ng/mL, P=0.006) and MMP-9 activity/tissue inhibitor of matrix metalloproteinase-1 ratios (P=0.018), although this difference did not reach statistical significance. There were significant correlations between the degree of changes in TNF-alpha and the degree of changes in MMP-9 activity (r=0.424, P=0.016). However, no significant correlations between lipoprotein levels or flow-mediated dilation percentages and levels of plaque stability markers were determined (-0.208 <= r <= 0.243). Conclusions-Simvastatin reduced serological markers of inflammation and plaque stability, independent of lipoprotein changes.