Vascular effects of diet and statin in hypercholesterolemic patients

Objective: We investigated whether statin improves nitric oxide (NO) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes, compared with American Heart Association Step I Diet (Diet). Methods: We administered diet+placebo and diet+simvastatin 20 mg daily during 14 weeks with randomized order to 31 and 32 patients with coronary artery disease, respectively, with a randomized design. Results: Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia and lowered plasma levels of tumor necrosis factor (TNF)-α, intercellular adhesion molecule type-1 (ICAM-1), serum levels of CRP, and fibrinogen (P<0.001, P<0.001, P=0.035, P<0.001 and P=0.014, respectively). Compared with diet alone, simvastatin lowered but statistically insignificant plasma levels of nitrate and malondialdehyde (MDA) (P=0.164 and P=0.150, respectively). Further, we observed that patients with the highest pretreatment TNF-α, ICAM-1, and CRP levels showed the greatest extent of reductions on simvastatin. There were significant inverse correlation between low-density lipoprotein (LDL) cholesterol or the ratio of LDL to HDL cholesterol levels and flow-mediated dilation percent (r=−0.342, P=0.009 and r=−0.356, P=0.006, respectively). Of interest, there were significant inverse correlations between flow-mediated dilation percent and TNF-α levels (r=−0.329, P=0.010). However, no significant correlations between lipoprotein levels and levels of inflammation markers were determined. Despite the significant changes of lipoproteins, diet alone did not decrease the markers of inflammation. Conclusions: Compared with diet alone, simvastatin significantly reduced markers of inflammation more. These effects were independent of lipoprotein changes.