Endothelial Dysfunction, Vascular Damage and Clinical Events
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- Virdis, A., Ghiadoni, L., Salvetti, G. et al. High Blood Press Cardiovasc Prev (2004) 11: 15. doi:10.2165/00151642-200411010-00004
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Impaired endothelial function due to reduced nitric oxide availability secondary to an augmented production of oxidative stress has been associated with an increased risk of cardiovascular events in patients with coronary artery disease. Therefore, improvement of endothelial function through antioxidant therapy might be an important therapeutic approach for the prevention of cardiovascular morbidity and mortality. Available evidence indicates that acute high-dose ascorbic acid (vitamin C) improves endothelial function in high-risk patients. In contrast, results from clinical trials on the effect of long-term antioxidant therapy are contradictory. This discrepancy could be due to different experimental designs, vascular areas, diseases, range of doses and concomitant drugs utilised. The possibility that antioxidant vitamins can reduce cardiovascular damage and prevent cardiovascular events has been investigated in several studies. While observational studies suggested an inverse relationship between antioxidant vitamin intake and progression of atherosclerotic lesions, controlled clinical studies showed no effect of antioxidant vitamins on post-percutaneous transluminal coronary angioplasty stenting restenosis, coronary and carotid atherosclerotic lesions. Controlled studies evaluating the effect of antioxidant vitamins, in particular tocopherol (vitamin E), on cardiovascular events showed no beneficial effect in six of eight trials, although data concerning both the presence or absence of benefit in particular patients and the type of cardiovascular events were discordant. Overall, while these data indicated that at this time antioxidant vitamins are not to be recommended for the prevention of cardiovascular events, they did not contradict the hypothesis that antioxidant therapy should still be considered an important tool for prevention-regression of atherosclerosis and prevention of cardiovascular events. However, this potential benefit needs to be confirmed by future controlled clinical studies using new antioxidant substances with optimal pharmacokinetics and pharmacodynamics, in order to achieve high bioavailability and a documented dose-dependent antioxidant effect.