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

• Published in: International journal of cardiology Vol. 97; no. 2; pp. 239 - 244
• Main Authors: Koh, Kwang Kon, Ahn, Jeong Yeal, Jin, Dong Kyu, Han, Seung Hwan, Kim, Hyung Sik, Choi, In Suck, Ahn, Tae Hoon, Shin, Eak Kyun, Jeong, Euy-Myoung
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.11.2004; Elsevier Science
• Subjects: Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Brachial Artery - drug effects; Cardiology. Vascular system; Coronary Artery Disease - blood; Coronary Artery Disease - complications; Disorders of blood lipids. Hyperlipoproteinemia; Female; Fenofibrate - pharmacology; Fibrate; HMG-CoA reductase inhibitor; Humans; Hyperlipidemia; Hyperlipidemias - blood; Hyperlipidemias - complications; Hypolipidemic Agents - pharmacology; Lipids - blood; Male; Matrix Metalloproteinases - blood; Matrix Metalloproteinases - drug effects; Medical sciences; Metabolic diseases; Middle Aged; Nitrates - blood; Nitric oxide; Nitric Oxide - metabolism; Plaque stability; Simvastatin - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Inhibitor of Metalloproteinase-1 - drug effects; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Vasodilation - drug effects; Plaque stability; Fibrate; Hyperlipidemia; HMG-CoA reductase inhibitor; Nitric oxide; Atherosclerosis; Stability; Enzyme; Cardiovascular disease; Metabolic diseases; Lipids; Metalloendopeptidases; Statin derivative; Nitric oxide: Plaque stability; Vascular disease; Peptidases; Hydrolases; Hyperlipemia; Inhibitor; Oxidoreductases; Dyslipemia; Comparative study; Reductase
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2003.09.007

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-α) 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-α 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.