Insights into oxidative stress and atherosclerosis.

Compelling evidence points to oxidative stress as an important trigger in the complex chain of events leading to atherosclerosis. Randomized clinical trials have not provided definitive evidence of the beneficial effect of antioxidant vitamins. Problems associated with the use of vitamins include their potential pro-oxidant effects and the decreased absorption of natural gamma-tocopherol caused by alpha-tocopherol supplements. Probucol and amlodipine are more powerful lipophilic antioxidants than vitamin E. They also do not appear to have significant pro-oxidant properties. Probucol has been shown to prevent coronary restenosis after balloon angioplasty in clinical trials. Its high density lipoprotein-lowering effect, however, prevents it from being protective against progression of coronary atherosclerosis. Slowing or reversing the atherosclerotic process with an antioxidant likely requires the use of a powerful lipophilic antioxidant that has neutral or positive effects on serum lipids when given alone or in combination with a lipid-lowering agent.