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

Abstract

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< or =r< or =0.243).

CONCLUSIONS:

Simvastatin reduced serological markers of inflammation and plaque stability, independent of lipoprotein changes.

• Authors: Kwang Kon Koh, Ji Won Son, Jeong Yeal Ahn, Dong Kyu Jin, Hyung Sik Kim, Yu Mi Choi, Dae Sung Kim, Euy-Myoung Jeong, Gi Soo Park, In Suck Choi, Eak Kyun Shin
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 9 Pg. e19-23 (Sep 01 2002) ISSN: 1524-4636 [Electronic] United States
• PMID: 12231575 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• C-Reactive Protein
• Simvastatin
• Matrix Metalloproteinases

Topics

• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Coronary Artery Disease (diet therapy, drug therapy, enzymology, metabolism)
• Diet
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypercholesterolemia (diet therapy, drug therapy, enzymology, metabolism)
• Inflammation (blood, diet therapy, drug therapy)
• Lipids (blood)
• Male
• Matrix Metalloproteinases (metabolism, physiology)
• Middle Aged
• Nitric Oxide (metabolism, physiology)
• Prospective Studies
• Simvastatin (pharmacology, therapeutic use)
• Single-Blind Method
• Tumor Necrosis Factor-alpha (metabolism)
• Vasomotor System (drug effects, metabolism, physiology)