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Does reduction in cardiac transplant oxidative stress using vitamin C and E reduce the progression of transplant-associated atherosclerosis? - Vitamin C and E and Transplant Atherosclerosis
Description:
Does reduction in cardiac transplant oxidative stress using vitamin C and E reduce the progression of transplant-associated atherosclerosis?
Study Design
Study Design:
Drug/Procedures Used:
A placebo controlled trial randomised 40 patients 0-2 years post-transplant to twice daily vitamin C 500mg plus vitamin E 400 IU or placebos. All patients received 40mg of pravastatin, steroids, cyclosporin, and azathioprine. Exclusion criteria included a coronary lesion >50% at time of initial study, and a creatinine > about 2mg/dl. Endpoints at 1 year included changes in coronary arteries as measured by quantitative coronary arteriography, IVUS (intimal index determined as intimal area divided by vessel area in defined sites), and vasoreactivity to acetylcholine and Ntg.
Principal Findings:
The average age of recipients was 51 and donors 32 years. 27 of the 40 pts entered the study at 3-8 weeks, 11 at 1 year and 2 at 2 years. More patients in the antioxidant group were IgG CMV positive. There was no difference at entry or follow-up in lipids. There was a highly significant increase in serum vitamin E and C in those assigned the vitamins. After 1 year the IVUS intimal index increased by 8% in the placebo group but did not change in the treatment group (0.8%), p = 0.008. Treatment was also associated with a reduction in maximal IMT vs an increase with placebo, and less increase in plaque area. There were no differences in vessel or lumen area, which decreased in both groups (negative remodeling). Coronary endothelial function remained stable in both groups.
Interpretation:
Supplemental antioxidant vitamin C and E retarded the early progression of transplant associated coronary atherosclerosis. The reduction in plaque growth attributed to the antioxidants was independent of endothelial function, which may have been stabilized by the pravastatin. Transplant atherosclerosis is concentric and fibroproliferative and the results should not be extended to lipid rich atheromatous disease. This small trial provides evidence for clinicians to consider antioxidant supplements to prevent transplant atherosclerosis. It is important to note they used the combination of vitamin E and C, which eliminates the pro-oxidant potential of isolated tocopherols. Further studies in larger numbers of patients are needed.
References:
Fang JC, Kinlay S, Beltrame J, et al. Effect of vitamins C and E on Progression of Transplant-associated Arteriosclerosis: A Randomised Trial. Lancet 2002;359:1108-13.
Keywords: Immunoglobulin G, Cyclosporine, Reactive Oxygen Species, Coronary Artery Disease, Follow-Up Studies, Atherosclerosis, Vitamin E, Lipids, Oxidative Stress, Creatinine, Heart Transplantation, Tunica Intima, Coronary Angiography, Azathioprine, Dietary Supplements, Tocopherols, Pravastatin
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