Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F 2 -Isoprostane Formation in Hypercholesterolemic Subjects: No Further Effect of Vitamin E

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-11, Vol.106 (20), p.2543-2549
• Main Authors: De Caterina, Raffaele, Cipollone, Francesco, Filardo, Francesca Paola, Zimarino, Marco, Bernini, Walter, Lazzerini, Guido, Bucciarelli, Tonino, Falco, Angela, Marchesani, Paola, Muraro, Raffaella, Mezzetti, Andrea, Ciabattoni, Giovanni
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000038500.43292.D7

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. Methods and 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 2α (8-iso-PGF 2α ) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF 2α 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 2α with vitamin E levels but a much stronger relationship with LDL cholesterol ( R 2 =0.162; P