Abstract 986: Vitamin E Reduces Cardiovascular Disease in Individuals With Diabetes Mellitus and the Haptoglobin 2–2 Genotype
Background. Individuals with both Diabetes Mellitus (DM) and the Haptoglobin (Hp) 2–2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2–2 protein is impaired we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2–2 DM individuals.
Methods. We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long term implications in a real-world population from Kaiser Permanente.
Results. Meta-analysis of the three trials demonstrated a significant overall reduction in the composite endpoint in Hp 2–2 DM individuals with vitamin E (odds ratio 0.58 (95% CI 0.40 – 0.86) p=0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite endpoint. In these trials, Hp typing of 31 DM individuals and treating with vitamin E those with the Hp 2–2 prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2–2 DM individuals in the Kaiser population would increase their life expectancy by approximately three years.
Conclusions. A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2–2 with vitamin E appears to be highly clinically effective.