title: Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet.
abstract: BACKGROUND
  Results of clinical trials of statin therapy demonstrate that an improvement in incidence of cardiovascular end points and coronary stenosis can be achieved. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that affect endothelial function, such as inflammatory responses, formation of thrombi, and stabilization of plaque.
  
  
  OBJECTIVE
  To investigate levels of serologic markers, which may be useful surrogates for activity of vascular disease after administration of statin.
  
  
  METHODS
  We administered 20-40 mg simvastatin daily for 14 weeks to 13 patients established to have coronary artery disease who remained hypercholesterolemic during step-II diet therapy.
  
  
  RESULTS
  Administration of simvastatin significantly lowered lipoprotein levels and the low: high-density lipoprotein cholesterol level ratio and apolipoprotein B:A-I level ratio compared with pretreatment values (P < 0.01). Administration of simvastatin significantly lowered plasma levels of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-I [33+/-46 and 13+/-19%, respectively (P = 0.027 and 0.020, respectively)]. Furthermore, administration of simvastatin tended to lower plasma levels of plasminogen activator inhibitor type-1 and tumor necrosis factor-alpha [by 20+/-44 and 13+/-29%, respectively (P= 0.066 and 0.110, respectively)]. There were significant inverse correlations between pretreatment levels of MMP-9 and the degree of change in those levels after administration of simvastatin (r = -0.714, P= 0.005). However, there was no significant correlation between levels of lipoprotein and levels of MMP-9, monocyte chemoattractant protein-I, and plasminogen activator inhibitor type-1 during administration of simvastatin.
  
  
  CONCLUSIONS
  Our current data support the hypothesis that nonlipid mechanisms elicited by administration of simvastatin contribute to the decrease in incidence of cardiovascular events and explain the early clinical benefit observed in clinical trials, independent of changes in levels of lipoprotein.
authors: Department of Cardiology, Gachon Medical School, Inchon, South Korea. kwangk@ghil.com
authors: K K
authors: KK
authors: Koh
authors: J W
authors: JW
authors: Son
authors: J Y
authors: JY
authors: Ahn
authors: Y M
authors: YM
authors: Choi
authors: D K
authors: DK
authors: Jin
authors: G S
authors: GS
authors: Park
authors: I S
authors: IS
authors: Choi
authors: M S
authors: MS
authors: Sohn
authors: E K
authors: EK
authors: Shin
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood*; D003627:Data Interpretation, Statistical; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D018932:Chemokine CCL2; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D019821:Simvastatin; D020780:Matrix Metalloproteinase 9