Cardiovascular antioxidant therapy: a review of supplements, pharmacotherapies, and mechanisms.

Oxidant stress plays an important role in the pathogenesis of atherosclerosis. In the late 1980s, biological studies demonstrated that oxygen-free radicals oxidize low-density lipoprotein-cholesterol, resulting in the creation of foam cells and inciting the cascade of biological events that ultimately result in the formation of atherosclerosis. In vitro studies showed the ability of antioxidant vitamins to scavenge free radicals and block the oxidation of low-density lipoprotein. This data was supported in vivo by early observational studies suggesting the benefit of antioxidants, particularly vitamin E, in the prevention of coronary artery disease. On the basis of these studies, the use of antioxidant supplements by the general population increased substantially and became a multibillion dollar industry. Despite strong biological evidence and promising observational data, more rigorous scientific evaluation did not support a causational relationship between vitamin supplements and lowering coronary artery disease risk. Several prospective, double-blind, placebo-controlled trials showed no benefit and possibly harmful effects. Therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, which are known to have benefit in preventing and treating atherosclerosis by reducing blood pressure and cholesterol, also have a "pleiotropic" effect in reducing the formation of reactive oxygen species (ROS). Advances in molecular biology and the study of ROS led to a better understanding of the mechanisms that govern their production and role in atherogenesis. This progress identified unforeseen pathways by which these drugs favorably alter the balance in ROS production, and have raised possibilities for future targeted therapies in the prevention of atherosclerosis.