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Emerging role for antioxidant therapy in protection against diabetic cardiac complications: experimental and clinical evidence for utilization of classic and new antioxidants.

Hill MF - Curr Cardiol Rev (2008)

Bottom Line: Diabetes mellitus (DM) markedly potentiates the risk of cardiovascular morbidity and mortality among individuals with diabetes as compared to the non-diabetic population.The excess mortality and poor prognosis of these patients results primarily from the development of recurrent MI and heart failure (HF).In this review, we provide the emergence of experimental and clinical evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of DM.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

ABSTRACT
Diabetes mellitus (DM) markedly potentiates the risk of cardiovascular morbidity and mortality among individuals with diabetes as compared to the non-diabetic population. After myocardial infarction (MI), DM patients have a higher incidence of death than do non-diabetics. The excess mortality and poor prognosis of these patients results primarily from the development of recurrent MI and heart failure (HF). Although several lines of evidence support a role for increased oxidative stress in a range of cardiovascular diseases, clinical trials examining the therapeutic efficacy of antioxidants have yielded conflicting results. The reasons for these incongruous results is multifactorial. An underlying theme has been lack of patient inclusion based on elevated indices of oxidative stress which could have diluted the population susceptible to benefit in the clinical trials. Laboratory evidence has accumulated indicating that oxidative stress is dramatically accentuated in cardiac abnormalities inherent in DM. In this review, we provide the emergence of experimental and clinical evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of DM. Specifically, focus will be directed on preclinical animal studies and human clinical trials that have tested the effect of antioxidant supplements on MI and HF events in the presence of DM.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier plot of the composite end point in Hp 2-2 DM individuals allocated to vitamin E or placebo. Events are CV death, myocardial infarction, or stroke. There were 726 Hp 2-2 individuals allocated to vitamin E and 708 Hp 2-2 individuals allocated to placebo. As a reflection of the 18-month window during which participants entered the study (time 0 being the day of Hp typing) and the early termination of the study not all participants were in the study for the same duration. This is reflected in the abscissa where the number of individuals in the study (the number at risk) for a given duration is provided. There were a total of 16 patients (2.2%) who had events in the vitamin E group and 33 patients who had events in the placebo group (4.7%). There was a significant decrease in the composite end point in the vitamin E group compared with the placebo group (HR 0.47 [95% CI 0.27 to 0.82], P=0.01 by log-rank). Reprinted from Ref. 104 (Copyright 2008), with permission from the American Heart Association, Inc. and Lippincott Williams & Wilkins.
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Figure 2: Kaplan-Meier plot of the composite end point in Hp 2-2 DM individuals allocated to vitamin E or placebo. Events are CV death, myocardial infarction, or stroke. There were 726 Hp 2-2 individuals allocated to vitamin E and 708 Hp 2-2 individuals allocated to placebo. As a reflection of the 18-month window during which participants entered the study (time 0 being the day of Hp typing) and the early termination of the study not all participants were in the study for the same duration. This is reflected in the abscissa where the number of individuals in the study (the number at risk) for a given duration is provided. There were a total of 16 patients (2.2%) who had events in the vitamin E group and 33 patients who had events in the placebo group (4.7%). There was a significant decrease in the composite end point in the vitamin E group compared with the placebo group (HR 0.47 [95% CI 0.27 to 0.82], P=0.01 by log-rank). Reprinted from Ref. 104 (Copyright 2008), with permission from the American Heart Association, Inc. and Lippincott Williams & Wilkins.

Mentions: The marked increase in lipid peroxidation products of arachidonic acid in the myocardium of DM Hp 2 mice occurring after myocardial ischemia-reperfusion [95] prompted Levy and colleagues to investigate whether antioxidant therapy with vitamin E might have reduced cardiovascular events in Hp 2-2 DM patients that participated in the HOPE (Heart Outcomes Prevention Evaluation) trial (23). Hp genotype was assessed in stored blood samples from HOPE. Analysis of this HOPE cohort showed that vitamin E treatment significantly reduced MI and cardiovascular death by 43% and 55%, respectively, in these Hp 2-2 DM individuals [103]. However, due to the retrospective nature of this analysis, Levy and colleagues sought to test the validity of these findings in Hp 2-2 DM patients in a prospective, double-blind, placebo controlled clinical trial of vitamin E [104]. 1434 DM patients with the Hp 2-2 genotype were randomized to vitamin E (400 U/day) or placebo [104]. At the first interim analysis, 18 months after initiating the study, cardiovascular events were found to be significantly reduced in the cohort of Hp 2-2 DM patients receiving vitamin E compared with placebo (Fig. 2), which led to an early termination of the study [104]. The reduction in cardiovascular events in the vitamin E-treated group of patients was in large part attributable to a significant reduction in the incidence of non-fatal MI [104]. These results suggest that this subgroup of DM patients, in particular, may derive cardiovascular benefit from treatment with the antioxidant vitamin E and in addition, provide further affirmation of the ability of vitamin E to reduce MI in the diabetic population.


Emerging role for antioxidant therapy in protection against diabetic cardiac complications: experimental and clinical evidence for utilization of classic and new antioxidants.

Hill MF - Curr Cardiol Rev (2008)

Kaplan-Meier plot of the composite end point in Hp 2-2 DM individuals allocated to vitamin E or placebo. Events are CV death, myocardial infarction, or stroke. There were 726 Hp 2-2 individuals allocated to vitamin E and 708 Hp 2-2 individuals allocated to placebo. As a reflection of the 18-month window during which participants entered the study (time 0 being the day of Hp typing) and the early termination of the study not all participants were in the study for the same duration. This is reflected in the abscissa where the number of individuals in the study (the number at risk) for a given duration is provided. There were a total of 16 patients (2.2%) who had events in the vitamin E group and 33 patients who had events in the placebo group (4.7%). There was a significant decrease in the composite end point in the vitamin E group compared with the placebo group (HR 0.47 [95% CI 0.27 to 0.82], P=0.01 by log-rank). Reprinted from Ref. 104 (Copyright 2008), with permission from the American Heart Association, Inc. and Lippincott Williams & Wilkins.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2801857&req=5

Figure 2: Kaplan-Meier plot of the composite end point in Hp 2-2 DM individuals allocated to vitamin E or placebo. Events are CV death, myocardial infarction, or stroke. There were 726 Hp 2-2 individuals allocated to vitamin E and 708 Hp 2-2 individuals allocated to placebo. As a reflection of the 18-month window during which participants entered the study (time 0 being the day of Hp typing) and the early termination of the study not all participants were in the study for the same duration. This is reflected in the abscissa where the number of individuals in the study (the number at risk) for a given duration is provided. There were a total of 16 patients (2.2%) who had events in the vitamin E group and 33 patients who had events in the placebo group (4.7%). There was a significant decrease in the composite end point in the vitamin E group compared with the placebo group (HR 0.47 [95% CI 0.27 to 0.82], P=0.01 by log-rank). Reprinted from Ref. 104 (Copyright 2008), with permission from the American Heart Association, Inc. and Lippincott Williams & Wilkins.
Mentions: The marked increase in lipid peroxidation products of arachidonic acid in the myocardium of DM Hp 2 mice occurring after myocardial ischemia-reperfusion [95] prompted Levy and colleagues to investigate whether antioxidant therapy with vitamin E might have reduced cardiovascular events in Hp 2-2 DM patients that participated in the HOPE (Heart Outcomes Prevention Evaluation) trial (23). Hp genotype was assessed in stored blood samples from HOPE. Analysis of this HOPE cohort showed that vitamin E treatment significantly reduced MI and cardiovascular death by 43% and 55%, respectively, in these Hp 2-2 DM individuals [103]. However, due to the retrospective nature of this analysis, Levy and colleagues sought to test the validity of these findings in Hp 2-2 DM patients in a prospective, double-blind, placebo controlled clinical trial of vitamin E [104]. 1434 DM patients with the Hp 2-2 genotype were randomized to vitamin E (400 U/day) or placebo [104]. At the first interim analysis, 18 months after initiating the study, cardiovascular events were found to be significantly reduced in the cohort of Hp 2-2 DM patients receiving vitamin E compared with placebo (Fig. 2), which led to an early termination of the study [104]. The reduction in cardiovascular events in the vitamin E-treated group of patients was in large part attributable to a significant reduction in the incidence of non-fatal MI [104]. These results suggest that this subgroup of DM patients, in particular, may derive cardiovascular benefit from treatment with the antioxidant vitamin E and in addition, provide further affirmation of the ability of vitamin E to reduce MI in the diabetic population.

Bottom Line: Diabetes mellitus (DM) markedly potentiates the risk of cardiovascular morbidity and mortality among individuals with diabetes as compared to the non-diabetic population.The excess mortality and poor prognosis of these patients results primarily from the development of recurrent MI and heart failure (HF).In this review, we provide the emergence of experimental and clinical evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of DM.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

ABSTRACT
Diabetes mellitus (DM) markedly potentiates the risk of cardiovascular morbidity and mortality among individuals with diabetes as compared to the non-diabetic population. After myocardial infarction (MI), DM patients have a higher incidence of death than do non-diabetics. The excess mortality and poor prognosis of these patients results primarily from the development of recurrent MI and heart failure (HF). Although several lines of evidence support a role for increased oxidative stress in a range of cardiovascular diseases, clinical trials examining the therapeutic efficacy of antioxidants have yielded conflicting results. The reasons for these incongruous results is multifactorial. An underlying theme has been lack of patient inclusion based on elevated indices of oxidative stress which could have diluted the population susceptible to benefit in the clinical trials. Laboratory evidence has accumulated indicating that oxidative stress is dramatically accentuated in cardiac abnormalities inherent in DM. In this review, we provide the emergence of experimental and clinical evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of DM. Specifically, focus will be directed on preclinical animal studies and human clinical trials that have tested the effect of antioxidant supplements on MI and HF events in the presence of DM.

No MeSH data available.


Related in: MedlinePlus