title: Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2-isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E.
abstract: BACKGROUND
  Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown.
  
  
  RESULTS
  We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63+/-11 years) to either simvastatin, to achieve >20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients' compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF(2alpha) was significantly reduced by simvastatin, from 361+/-148 pg/mg creatinine (mean+/-SD) at baseline to 239+/-124 pg/mg creatinine after 1 month. The addition of vitamin E did not reduce such levels any further (256+/-125 after 1 month). Linear regression analysis showed a weak inverse relationship of 8-iso-PGF(2alpha) with vitamin E levels but a much stronger relationship with LDL cholesterol (R(2)=0.162; P<0.001).
  
  
  CONCLUSIONS
  In hypercholesterolemic patients, LDL cholesterol is a major correlate of oxidative stress. Concomitant with LDL cholesterol reduction, simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation, which is a major determinant of vitamin E bioactivity.
authors.affiliation: Chair of Cardiology, G. d'Annunzio University, Chieti, Italy. rdecater@unich.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipollone
authors.forename: Francesca Paola
authors.initials: FP
authors.lastname: Filardo
authors.forename: Marco
authors.initials: M
authors.lastname: Zimarino
authors.forename: Walter
authors.initials: W
authors.lastname: Bernini
authors.forename: Guido
authors.initials: G
authors.lastname: Lazzerini
authors.forename: Tonino
authors.initials: T
authors.lastname: Bucciarelli
authors.forename: Angela
authors.initials: A
authors.lastname: Falco
authors.forename: Paola
authors.initials: P
authors.lastname: Marchesani
authors.forename: Raffaella
authors.initials: R
authors.lastname: Muraro
authors.forename: Andrea
authors.initials: A
authors.lastname: Mezzetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D018592:Cross-Over Studies; D015237:Dinoprost / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D028441:F2-Isoprostanes / Q000652:urine*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010349:Patient Compliance; D019821:Simvastatin / Q000627:therapeutic use*; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008078:Cholesterol, LDL; D028441:F2-Isoprostanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D002784:Cholesterol; D019821:Simvastatin; D015237:Dinoprost