Comparative effects of statin and fibrate on nitric oxide bioactivity and matrix metalloproteinase in hyperlipidemia.
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.
Cardiology, Gachon Medical School, Incheon, South Korea. kwangk@ghil.com
Kwang Kon
KK
Koh
Jeong Yeal
JY
Ahn
Dong Kyu
DK
Jin
Seung Hwan
SH
Han
Hyung Sik
HS
Kim
In Suck
IS
Choi
Tae Hoon
TH
Ahn
Eak Kyun
EK
Shin
Euy-Myoung
EM
Jeong
D001916:Brachial Artery / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D000960:Hypolipidemic Agents; D008055:Lipids; D009566:Nitrates; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019821:Simvastatin; D020782:Matrix Metalloproteinases; D011345:Fenofibrate