title: The effect of simvastatin on asymmetric dimethylarginine and flow-mediated vasodilation after optimizing the LDL level: a randomized, placebo-controlled study.
abstract: Research of statin influence on asymmetric dimethylarginine (ADMA) and flow-mediated vasodilatation (FMD) reveals controversial results. The aim of this study was to investigate the effects of moderate (40mg) and high (80mg) simvastatin doses on the levels of ADMA, total homocysteine (tHcy) and %FMD in patients with newly diagnosed severe hypercholesterolemia, after optimizing the LDL level. The study included 650 patients with severe hypercholesterolemia (total cholesterol≥7.5mmol/l; LDL≥4.9mmol/l). The treatment groups were administered 80mg simvastatin over a period of one month. The results indicated a reduction in ADMA and tHcy levels and an increase in %FMD in the treatment groups, compared with the control groups (receiving placebo or 40mg simvastatin). There was a statistically significant correlation between the %FMD changes and the baseline levels of Apo-B, ADMA and tHcy, as well as between the %ADMA changes and %LDL, % apolipoprotein-B and %tHcy-changes in patients on 80mg Simvastatin. A statistical linear regression analysis (in the treatment group) indicated that the baseline ADMA level is the most important statistically significant predictor related to %FMD-changes. A linear regression analysis additionally documented that % apolipoprotein-B-changes is a predictor of %ADMA-changes. In conclusion, in cases with optimized LDL-target levels (patients on 80mg Simvastatin), the baseline level of ADMA appears to be a major modulator of %FMD-changes.
authors: Clinic of Cardiology, University of Medicine, Plovdiv, Bulgaria. kitov@vip.bg
authors: Lyudmila G
authors: LG
authors: Vladimirova-Kitova
authors: Tanya I
authors: TI
authors: Deneva-Koycheva
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C487735:dimethylarginine; D006710:Homocysteine; D001120:Arginine; D019821:Simvastatin