title: ApoE isoforms, treatment of diabetes and the risk of coronary heart disease.
abstract: OBJECTIVE
  To analyze the risk of coronary heart disease in patients with type 2 diabetes mellitus (T2DM) receiving standard medical treatment.
  
  
  METHODS
  We performed a retrospective chart analysis of 269 middle-aged patients (age 45-64 years, mean age, 53.9 ± 5.5 years) with T2DM and without atherosclerotic cardiovascular events who underwent typing to determine their apolipoprotein E (apoE) isoforms. The apoE isoforms were determined using isoelectric focusing, followed by immunoblotting. We retrospectively evaluated the charts of the 269 patients, recorded between their first visit to the hospital (the study's start point, between 1987 and 1992) and the occurrence of an atherosclerotic cardiovascular event (the study's endpoint) or January 2004, whichever came first. The age-adjusted mean values and the prevalences of covariates were calculated to compare the laboratory data among the apoE phenotypes. To investigate the association of risk factors with the incidence of coronary heart disease during the follow-up period, monovariate and multivariate Cox regression models were used.
  
  
  RESULTS
  At enrollment, the mean serum low density lipoprotein (LDL) cholesterol levels were lowest (2.92 ± 0.89 mmol/L) among the subjects with apoE2 (apoE2/2 or apoE2/3) and highest (3.52 ± 0.77 mmol/L) among the subjects with apoE4 (apoE3/4 or apoE4/4). No significant differences in mean age or the percentage of smokers were observed among the three groups. Furthermore, no significant differences were observed in the systolic and diastolic blood pressures, body mass index, HbA1c level or serum triglyceride levels among the three groups. There were 47 cases of coronary heart disease over 3285 person-years of follow-up. An age-adjusted multivariate Cox proportional model identified diabetic retinopathy (hazard ratio, 2.38, 95% CI: 1.28-4.43, P = 0.006), a high systolic blood pressure (hazard ratio, 1.04, 95% CI: 1.02-1.06, P < 0.001) and high HbA1c values (hazard ratio, 1.19, 95% CI: 1.02-1.38, P = 0.0029), but not the LDL cholesterol value at enrollment (hazard ratio, 1.01, 95% CI: 0.97-1.05, P = 0.77) nor the specific apoE isoform, as significant predictors of coronary heart disease.
  
  
  CONCLUSIONS
  Under standard medical treatment of diabetes, including the control of LDL cholesterol levels, the apoE4 isoform was not associated with coronary heart disease among T2DM patients.
authors.affiliation: Hideki Ehara, Hiroji Kitazato, Shoji Kawazu, Yasuo Akanuma, the Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Nihonbashi-bakurocho, Chuo-ku, Tokyo 103-0002, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ehara
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Yamamoto-Honda
authors.forename: Hiroji
authors.initials: H
authors.lastname: Kitazato
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawazu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Akanuma
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Noda