title: Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy.
abstract: OBJECTIVE
  Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes. However, data from randomized clinical trials are limited. Therefore, we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes.
  
  
  METHODS
  The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized clinical trial with a 2 x 2 factorial design, which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events. Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor. The study was designed to recruit a large number of people with diabetes, and the analyses of the effects of vitamin E in this group were preplanned. Patients were randomly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years. The primary study outcome was the composite of myocardial infarction, stroke, or CV death. Secondary outcomes included total mortality, hospitalizations for heart failure, hospitalizations for unstable angina, revascularizations, and overt nephropathy.
  
  
  RESULTS
  There were 3,654 people with diabetes. Vitamin E had a neutral effect on the primary study outcome (relative risk = 1.03, 95% CI 0.88-1.21; P = 0.70), on each component of the composite primary outcome, and on all predefined secondary outcomes.
  
  
  CONCLUSIONS
  The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and/or additional coronary risk factor(s) has no effect on CV outcomes or nephropathy.
authors.affiliation: Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada. lonnem@mcmaster.ca
authors.forename: Eva
authors.initials: E
authors.lastname: Lonn
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Byrcon
authors.initials: B
authors.lastname: Hoogwerf
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.forename: Qilong
authors.initials: Q
authors.lastname: Yi
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Gilles
authors.initials: G
authors.lastname: Dagenais
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006331:Heart Diseases / Q000145:classification; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality; D010919:Placebos; D020521:Stroke / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D010919:Placebos; D014810:Vitamin E