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      Effects of Vitamins C and E on the Outcome after Acute Myocardial Infarction in Diabetics: A Retrospective, Hypothesis-Generating Analysis from the MIVIT Study

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          Background: There is significant evidence that reactive oxygen species play an important role in endothelial dysfunction, ischemia/reperfusion injury as well as in the pathogenesis of diabetes mellitus (DM). It is also known that vitamins C and E have substantial antioxidant properties. However, clinical evidence concerning this topic is insufficient so far. The aim of the present study was to determine if the administration of vitamins C and E influences the outcome in diabetic patients with acute myocardial infarction (AMI). Methods: Among 800 patients with AMI included in the MIVIT (Myocardial Infarction and Vitamins) study, 122 patients (15%) had confirmed DM. A retrospective analysis of the influence of vitamins C and E on 30-day cardiac mortality in patients with or without DM was performed. Results: There was a significant reduction in 30-day cardiac mortality in diabetic patients treated with antioxidant vitamins C and E [5 (8%) vs. 14 (22%); OR 0.32, 95% CI 0.11–0.93; p = 0.036]. Such an effect has not been observed in patients without DM [19 (6%) vs. 19 (6%); OR 0.97, 95% CI 0.51–1.85; p = 0.94]. Conclusion: The results suggest that early administration of antioxidant vitamins C and E in patients with AMI and concomitant DM reduces cardiac mortality.

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          Most cited references 7

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          Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.

           S Yusuf,  J Pogue,  P Bosch (2000)
          Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis. We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor. These patients were randomly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor (ramipril) or matching placebo for a mean of 4.5 years (the results of the comparison of ramipril and placebo are reported in a companion article). The primary outcome was a composite of myocardial infarction, stroke, and death from cardiovascular causes. The secondary outcomes included unstable angina, congestive heart failure, revascularization or amputation, death from any cause, complications of diabetes, and cancer. A total of 772 of the 4761 patients assigned to vitamin E (16.2 percent) and 739 of the 4780 assigned to placebo (15.5 percent) had a primary outcome event (relative risk, 1.05; 95 percent confidence interval, 0.95 to 1.16; P=0.33). There were no significant differences in the numbers of deaths from cardiovascular causes (342 of those assigned to vitamin E vs. 328 of those assigned to placebo; relative risk, 1.05; 95 percent confidence interval, 0.90 to 1.22), myocardial infarction (532 vs. 524; relative risk, 1.02; 95 percent confidence interval, 0.90 to 1.15), or stroke (209 vs. 180; relative risk, 1.17; 95 percent confidence interval, 0.95 to 1.42). There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause. There were no significant adverse effects of vitamin E. In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.
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            MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.

            It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. 20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of alpha-tocopherol, increased that of vitamin C by one-third, and quadrupled that of beta-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome.
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              Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial.

              Cardiac transplantation is associated with oxidant stress, which may contribute to the development of accelerated coronary arteriosclerosis. We postulated that treatment with antioxidant vitamins C and E would retard the progression of transplant-associated arteriosclerosis. In a double-blind prospective study, 40 patients (0-2 years after cardiac transplantation) were randomly assigned vitamin C 500 mg plus vitamin E 400 IU, each twice daily (n=19), or placebo (n=21) for 1 year. The primary endpoint was the change in average intimal index (plaque area divided by vessel area) measured by intravascular ultrasonography (IVUS). Coronary endothelium-dependent vasoreactivity was assessed with intracoronary acetylcholine infusions. IVUS, coronary vasoreactivity, and vitamin C and E plasma concentrations were assessed at baseline and at 1 year follow-up. All patients received pravastatin. Analyses were by intention to treat. Vitamin C and E concentrations increased in the vitamin group (vitamin C 43 [SD 21] to 103 [43] mmol/L; vitamin E 24 [14] to 65 [27] mmol/L) but did not change in the placebo group (vitamin C 45 [15] vs 43 [16] mmol/L; vitamin E 27 [14] vs 27 [9] mmol/L; p<0.0001 for difference between groups). During 1 year of treatment, the intimal index increased in the placebo group by 8% (SE 2) but did not change significantly in the treatment group (0.8% [1]; p=0.008). Coronary endothelial function remained stable in both groups. Supplementation with antioxidant vitamins C and E retards the early progression of transplant-associated coronary arteriosclerosis.

                Author and article information

                S. Karger AG
                January 2009
                12 August 2008
                : 112
                : 3
                : 219-223
                aPostgraduate Medical School, Department of Cardiology, Grochowski Hospital, and bMedical Research Center, Polish Academy of Sciences, Warsaw, Poland
                151239 Cardiology 2009;112:219–223
                © 2008 S. Karger AG, Basel

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                Figures: 1, Tables: 1, References: 14, Pages: 5
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