Abstract 5053: Discontinuation of Vitamin E Results in a Dramatic Increase in the Incidence of Myocardial Infarction and a Rapid Deterioration of HDL Function in Individuals with Diabetes Mellitus and the Hp 2–2 Genotype
To determine the relative incidence of myocardial infarction (MI) and the quality of HDL in individuals with DM and the Hp 2–2 genotype in whom vitamin E has been withdrawn
Background: Individuals with the Hp 2–2 genotype and DM representing approximately 50% of all individuals with DM have been shown to have a 2–5 fold increased incidence of CVD (MI and CVD death) as compared to individuals without the Hp 2–2 genotype. We have shown that this may be due to severe HDL dysfunction in Hp 2–2 DM individuals. We have recently demonstrated in ICARE, a prospective randomized trial comparing vitamin E to placebo in Hp 2–2 DM individuals, that in those individuals who received vitamin E the incidence of MI was dramatically decreased as compared to those individuals who received placebo (p=0.004 by log rank). We prospectively determined the incidence of MI in ICARE participants after vitamin E was discontinued. In a small cohort of Hp 2–2 DM individuals we assessed HDL function (stimulation of cholesterol efflux from macrophages) after treatment with vitamin E or placebo in a crossover design. In those individuals treated in ICARE with vitamin E the incidence of MI increased dramatically in the period after ICARE was terminated and vitamin E withdrawn (MI incidence of 0.4% on vitamin E vs. 1.8% off vitamin E, p=0.03). Furthermore, in the 15 month interval after ICARE was terminated the incidence of MI was not significantly different in those individuals who had received vitamin E vs. placebo (MI incidence of 1.8% in individuals who had received vitamin E vs. MI incidence of 1.7% in individuals who had received placebo, p=0.9). HDL function was significantly improved in Hp 2–2 individuals by vitamin E. However, only 2 months after vitamin E was withdrawn HDL function had deteriorated to its level of dysfunction prior to the initiation of vitamin E. Discontinuation of vitamin E is associated with an abrupt increase in the incidence of MI and a deterioration of HDL function in Hp 2–2 DM individuals. These studies support the pharmacogenomic application of the Hp genotype to determine whether an individual with DM should receive vitamin E.