Abstract 1245: The Mortality Rate from Cardiovascular Disease is more than Five Times Higher in Individuals with Diabetes Mellitus who have the Hp 2–2 Genotype as Compared to Individuals with Diabetes Mellitus who do not have the Hp 2–2 Genotype
Objective: To determine if the Haptoglobin (Hp) genotype can predict the risk of death from cardiovascular disease in individuals with Diabetes Mellitus (DM) in a prospective community based longitudinal study. Background: The Hp gene is polymorphic in man with two classes of alleles denoted 1 and 2. Retrospective analysis of 5 longitudinal studies has demonstrated that the Hp genotype is a major determinant of the risk of incident CVD in DM individuals. Specifically, individuals with the Hp 2–2 genotype and DM were found to have a 2–5 fold increased risk of CVD as compared to Hp 1–1 or Hp 2–1 DM individuals.
Method: 2241 individuals with DM ≥55 years of age from 47 primary health care clinics were Hp genotyped and followed prospectively for three years for incident myocardial infarction, stroke and death (all cause and cardiovascular). All aspects of the medical care of individuals in the cohort were left to the discretion of the patient’s physician.
Results: The cohort consisted of 708 individuals with the Hp 2–2 genotype and 1533 individuals with the Hp 1–1 or 2–1 genotype. At baseline there were no significant differences between individuals with and without the Hp 2–2 genotype in their DM characteristics (HbA1c, duration) or in the prevalence of cardiovascular disease (25% in both groups). During the nearly 3 year period of follow up total mortality was increased in individuals with the Hp 2–2 genotype (2.5% vs 1.8%, HR 0.68, CI 0.35–1.25, p=0.2 by log rank). These differences in overall mortality were the result of a greater than 5 fold increase in CV death in Hp 2–2 individuals (1.1% vs 0.2%, HR 0.15, CI 0.038 – 0.44, p=0.001 by log rank). The incidence of non fatal MI was increased by over 50% in the Hp 2–2 group (3.9% vs. 2.5%, p=0.068). These differences were unaffected by adjustment for DM characteristics and conventional cardiovascular risk factors.
Conclusions. DM individuals with the Hp 2–2 genotype are at a dramatically increased risk of death due to cardiovascular disease. Pharmacogenomic treatment strategies targeted to this high risk population may provide considerable public health and economic benefit.