European Heart Journal Advance Access published online on December 6, 2007
European Heart Journal, doi:10.1093/eurheartj/ehm565
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Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E
1 IV Divisione di Clinica Medica, Department of Experimental Medicine and Pathology, University of Rome ‘La Sapienza’, Viale del Policlinico 155, Rome 00161, Italy
2 Fondazione Livio Patrizi Research Laboratories, Rome, Italy
3 Department of Internal Medicine, University of Rome ‘Tor Vergata’, Rome, Italy
Received 18 May 2007; revised 2 November 2007; accepted 12 November 2007.
* Corresponding author. Tel: +39 064461933, Fax: +39 0649970893, E-mail: francesco.violi{at}uniroma1.it
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.
Key Words: Statins • Oxidative stress • Vitamin E • Hypercholesterolaemia
These authors equally contributed to the Study
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