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


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.
Koh
Kwang Kon
KK
Department of Cardiology, Gachon Medical School, Incheon, Korea. kwangk@ghil.com
Son
Ji Won
JW
Ahn
Jeong Yeal
JY
Jin
Dong Kyu
DK
Kim
Hyung Sik
HS
Choi
Yu Mi
YM
Kim
Dae Sung
DS
Jeong
Euy-Myoung
EM
Park
Gi Soo
GS
Choi
In Suck
IS
Shin
Eak Kyun
EK
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000178:diet therapy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D004032:Diet; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D011446:Prospective Studies; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin; D020782:Matrix Metalloproteinases