title: Vascular effects of diet and statin in hypercholesterolemic patients.
abstract: OBJECTIVE
  We investigated whether statin improves nitric oxide (NO) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes, compared with American Heart Association Step I Diet (Diet).
  
  
  METHODS
  We administered diet+placebo and diet+simvastatin 20 mg daily during 14 weeks with randomized order to 31 and 32 patients with coronary artery disease, respectively, with a randomized design.
  
  
  RESULTS
  Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia and lowered plasma levels of tumor necrosis factor (TNF)-alpha, intercellular adhesion molecule type-1 (ICAM-1), serum levels of CRP, and fibrinogen (P<0.001, P<0.001, P=0.035, P<0.001 and P=0.014, respectively). Compared with diet alone, simvastatin lowered but statistically insignificant plasma levels of nitrate and malondialdehyde (MDA) (P=0.164 and P=0.150, respectively). Further, we observed that patients with the highest pretreatment TNF-alpha, ICAM-1, and CRP levels showed the greatest extent of reductions on simvastatin. There were significant inverse correlation between low-density lipoprotein (LDL) cholesterol or the ratio of LDL to HDL cholesterol levels and flow-mediated dilation percent (r=-0.342, P=0.009 and r=-0.356, P=0.006, respectively). Of interest, there were significant inverse correlations between flow-mediated dilation percent and TNF-alpha levels (r=-0.329, P=0.010). However, no significant correlations between lipoprotein levels and levels of inflammation markers were determined. Despite the significant changes of lipoproteins, diet alone did not decrease the markers of inflammation.
  
  
  CONCLUSIONS
  Compared with diet alone, simvastatin significantly reduced markers of inflammation more. These effects were independent of lipoprotein changes.
authors.affiliation: Vascular Medicine and Atherosclerosis Unit, Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, South Korea. kwank@ghil.com
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Koh
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Son
authors.forename: Jeong Yeal
authors.initials: JY
authors.lastname: Ahn
authors.forename: Dong Kyu
authors.initials: DK
authors.lastname: Jin
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Ahn
authors.forename: Dae Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Eak Kyun
authors.initials: EK
authors.lastname: Shin
mesh_terms: D015415:Biomarkers; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects; D003327:Coronary Disease / Q000628:therapy; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000188:drug therapy*; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D019821:Simvastatin