Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E

Eur Heart J. 2008 Jan;29(1):54-62. doi: 10.1093/eurheartj/ehm565. Epub 2007 Dec 6.

Abstract

Aims: Statins inhibit oxidative stress, but the interplay between cholesterol lowering and antioxidant vitamins is still unclear. Aims of the study were to assess if statins inhibit oxidative stress independently from cholesterol lowering, to assess the behaviour of vitamin E simultaneously with the changes of oxidative stress, to determine in vitro if atorvastatin was able to directly influence platelet-mediated LDL oxidation and vitamin E consumption.

Methods and results: In 30 hypercholesterolaemic patients (HC) and 20 healthy subjects (HS), urinary isoprostanes and plasma vitamin E were determined. The HC were randomized to diet or diet plus atorvastatin 10 mg/day. Compared with HS, HC had higher isoprostanes and lower vitamin E levels. The statin-allocated group showed a reduction of isoprostanes after only 3 days (-18.8%, P < 0.01); after 30 days, a stronger reduction of isoprostanes was noted (-37.1%, P < 0.01) whereas an increase of vitamin E (+42%, P < 0.01) and a reduction of cholesterol (-24.9%, P < 0.01) were observed. The diet-allocated group showed a weak decrease of cholesterol after 30 days. In vitro study showed that atorvastatin dose-dependently inhibited platelet-mediated LDL oxidation and isoprostane formation with a mechanism involving NADPH-oxidase.

Conclusion: The study provides the first evidence that atorvastatin exerts an early antioxidant effect that could contribute to enhancing circulating vitamin E.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Cholesterol, LDL / drug effects
  • Cholesterol, LDL / pharmacology
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hypercholesterolemia / diet therapy
  • Hypercholesterolemia / drug therapy*
  • Isoprostanes / metabolism
  • Male
  • Middle Aged
  • NADPH Oxidases / drug effects
  • Oxidative Stress / drug effects*
  • Pyrroles / therapeutic use*
  • Superoxides / metabolism
  • Vitamin E / blood*

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Heptanoic Acids
  • Isoprostanes
  • Pyrroles
  • Superoxides
  • Vitamin E
  • Atorvastatin
  • NADPH Oxidases