Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix metalloproteinase in hyperlipidemia.

Abstract

OBJECTIVE:

Because the lipoprotein effects of statin and fibric acid derivatives therapies differ, we studied the effects of these therapies in patients with hyperlipidemia on lipoproteins, vasomotor function, and plaque stability.

METHODS:

We administered simvastatin, 20 mg daily, to 27 patients with hypercholesterolemia and coronary artery disease, or fenofibrate, 200 mg daily, to 27 patients with pure hypertriglyceridemia during 8 weeks.

RESULTS:

As expected, simvastatin significantly lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) more, and fenofibrate decreased triglyceride and increased high-density lipoprotein cholesterol (HDL-C) more than either therapy. Simvastatin and fenofibrate significantly improved the percent flow-mediated dilator response to hyperemia by 183+/-41% and by 30+/-7%, respectively (each P<0.001); however, simvastatin significantly improved more (P<0.001). Simvastatin and fenofibrate significantly lowered plasma levels of tumor necrosis factor alpha (TNF-alpha) by 13+/-4% and by 10+/-4%, respectively (P=0.009 and P=0.006, respectively) with a similar degree (P=0.614). Simvastatin significantly reduced plasma levels of total MMP-9 and TIMP-1 more (P=0.005 and P=0.036, respectively), compared with fenofibrate showing no reduction. There were significant correlations between the degree of changes in TNF-alpha and the degree of changes in MMP-9 activity (r=0.376, P=0.053).

CONCLUSIONS:

Simvastatin and fenofibrate demonstrated antiatherosclerotic effects via different mechanisms.

• Authors: Kwang Kon Koh, Jeong Yeal Ahn, Dong Kyu Jin, Seung Hwan Han, Hyung Sik Kim, In Suck Choi, Tae Hoon Ahn, Eak Kyun Shin, Euy-Myoung Jeong
• Journal: International journal of cardiology (Int J Cardiol) Vol. 97 Issue 2 Pg. 239-44 (Nov 2004) ISSN: 0167-5273 [Print] Netherlands
• PMID: 15458690 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Hypolipidemic Agents
• Lipids
• Nitrates
• Tissue Inhibitor of Metalloproteinase-1
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Simvastatin
• Matrix Metalloproteinases
• Fenofibrate

Topics

• Brachial Artery (drug effects)
• Coronary Artery Disease (blood, complications)
• Female
• Fenofibrate (pharmacology)
• Humans
• Hyperlipidemias (blood, complications)
• Hypolipidemic Agents (pharmacology)
• Lipids (blood)
• Male
• Matrix Metalloproteinases (blood, drug effects)
• Middle Aged
• Nitrates (blood)
• Nitric Oxide (metabolism)
• Simvastatin (pharmacology)
• Tissue Inhibitor of Metalloproteinase-1 (blood, drug effects)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)
• Vasodilation (drug effects)