Abstract 10487: Vitamin E Supplementation is Associated With Increased Cardiovascular Disease and Mortality in Individuals With the Hp 2-1 Genotype and Diabetes
Introduction: Several large clinical trials and meta-analysis have demonstrated that vitamin E supplementation does not provide any measure of cardiovascular protection and may actually increase mortality. We have previously presented data from the HOPE and ICARE studies that a subgroup of individuals with Diabetes Mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype (about 36% of all DM individuals) have an overall reduction of 40% in the incidence of major cardiovascular events and a 20% decline in mortality with vitamin E supplementation. Taken together-a failure to show benefit from vitamin E overall in individuals with or without DM and a dramatic benefit from vitamin E in one-third of the DM population-these data would suggest that vitamin E is harmful to some part of the non Hp 2-2 DM cohort. Demonstration of such a divergent effect between the Hp genotype and vitamin E on CVD events would provide a compelling argument for the application of a pharmogenomic paradigm in which all DM individuals would be Hp typed and then only those with the Hp 2-2 genotype treated with vitamin E.
Hypothesis: We proposed that vitamin E may increase CVD and mortality in a subgroup of non Hp 2-2 diabetic individuals, specifically those with the Hp 1-1 or Hp 2-1 genotypes.
Methods: The ICARE study did not involve a group of non Hp 2-2 DM individuals in which to test this hypothesis. We therefore Hp typed an additional cohort, WHS, in which to test this hypothesis along side of HOPE. Hp type was assessed by gel electrophoresis.
Results: While vitamin E supplementation was associated with a reduction in CVD events and total mortality in Hp 2-2 DM individuals in HOPE, ICARE and WHS, it appeared to be associated with an increase in CVD events in HOPE and CVD events and total mortality in WHS in Hp 2-1 DM individuals (50% of all DM individuals). In HOPE and WHS vitamin E was associated with an 11% and 35% increase respectively in CVD events in Hp 2-1 DM individuals. Stroke was significantly increased 4.5 fold in Hp 2-1 DM individuals with vitamin E. Moreover, in WHS vitamin E supplementation was associated with a nearly 40% increase in total mortality in Hp 2-1 DM individuals.
Conclusions: The benefit or harm of vitamin E supplementation in individuals with DM appears to be dependent on the Hp genotype.
- © 2010 by American Heart Association, Inc.