Vascular effects of diet and statin in hypercholesterolemic patients.

Abstract

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)-alpha, 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-alpha, 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-alpha 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.

• Authors: Kwang Kon Koh, Ji Won Son, Jeong Yeal Ahn, Dong Kyu Jin, Hyung Sik Kim, Yu Mi Choi, Tae Hoon Ahn, Dae Sung Kim, Eak Kyun Shin
• Journal: International journal of cardiology (Int J Cardiol) Vol. 95 Issue 2-3 Pg. 185-91 (Jun 2004) ISSN: 0167-5273 [Print] Netherlands
• PMID: 15193818 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Cell Adhesion Molecules
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• C-Reactive Protein
• Simvastatin

Topics

• Biomarkers
• C-Reactive Protein (drug effects, metabolism)
• Cell Adhesion Molecules (drug effects)
• Coronary Disease (therapy)
• Endothelium, Vascular (drug effects)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypercholesterolemia (diet therapy, drug therapy)
• Inflammation (physiopathology)
• Male
• Middle Aged
• Oxidative Stress (drug effects)
• Simvastatin (pharmacology, therapeutic use)
• Statistics, Nonparametric