Abstract 3692: Tight Diabetic Glycemic Control Reduces the Risk of Cardiovascular Disease Only in Individuals with the Hp 2–2 Genotype

Abstract

Background. The Haptoglobin (Hp) gene is polymorphic in man with two classes of alleles denoted 1 and 2. Several cross sectional and retrospective analysis have suggested that the Hp genotype may be a major determinant of susceptibility to diabetic CVD. We sought to examine this relationship in a prospective population based study. Methods. We recruited over 3000 individuals 55 years of age or older with DM from 47 primary health care clinics of the Clalit Health Plan in Northern Israel and obtained a Hp genotype on all of these individuals. The prevalence of CVD at baseline was 25%. Patients were followed for two years, for the primary composite outcome of the study which was incident non-fatal myocardial infarction, stroke and CV death. Results. We found that the Hp 2–2 genotype was associated with a highly significant increase in the incidence of myocardial infarction, stroke and CV death. Moreover, after stratification of patients by baseline HbA1c to those above and below 7.0, representing inadequate or adequate glycemic control as currently recommended by the AHA and ADA, only in Hp 2–2 individuals was poor glycemic control found to be associated with an increased risk of major cardiovascular events. Conclusions. Optimal utilization of health care resources for risk factor modification should be focused on DM individuals with the Hp 2–2 genotype. Benefit from tight glycemic control only in a subset of the DM cohort defined by the Hp 2–2 genotype may explain the inability to show a benefit from tight glycemic control on reducing cardiovascular events in the entire DM cohort in multiple prior clinical studies.