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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:e19.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Comparative Effects of Diet and Statin on NO Bioactivity and Matrix Metalloproteinases in Hypercholesterolemic Patients With Coronary Artery Disease

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

From the Departments of Cardiology (K.K.K., J.W.S., D.K.J., G.S.P., I.S.C., E.K.S.), Clinical Pathology (J.Y.A.), Radiology (H.S.K.), Nutrition (Y.M.C.), and Preventive Medicine (Biostatistics) (D.S.K.), Gachon Medical School, Incheon, Korea, and the Department of Genetic Engineering (E.-M.J.), Sungkyunkwan University, Suwon, Korea.

Correspondence to Kwang Kon Koh, MD, FACC, HAHA, Professor of Medicine, Director, Vascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea 405-760. E-mail kwangk{at}ghil.com

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)-, 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- 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- 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 (-0.208r0.243).

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

Key Words: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors • endothelial function • nitric oxide • plaque stability • atherosclerosis

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