{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:57:55Z","timestamp":1793163475183,"version":"4.5.0"},"reference-count":26,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,11,1]]},"abstract":"<jats:p>OBJECTIVES\u2014Experimental 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.<\/jats:p>\n                  <jats:p>RESEARCH DESIGN AND METHODS\u2014The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized clinical trial with a 2 \u00d7 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.<\/jats:p>\n                  <jats:p>RESULTS\u2014There 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\u20131.21; P = 0.70), on each component of the composite primary outcome, and on all predefined secondary outcomes.<\/jats:p>\n                  <jats:p>CONCLUSIONS\u2014The 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.<\/jats:p>","DOI":"10.2337\/diacare.25.11.1919","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T17:51:27Z","timestamp":1173117087000},"page":"1919-1927","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":297,"title":["Effects of Vitamin E on Cardiovascular and Microvascular Outcomes in High-Risk Patients With Diabetes"],"prefix":"10.2337","volume":"25","author":[{"given":"Eva","family":"Lonn","sequence":"first","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byrcon","family":"Hoogwerf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice","family":"Pogue","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Dagenais","sequence":"additional","affiliation":[{"name":"the Quebec Heart Institute, Laval University, Ste-Foy, Quebe\u0301c, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F.E.","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Schwabing General Hospital, Ludwig Maximilians University, Munchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hertzel C.","family":"Gerstein","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the Heart Outcomes Prevention Evaluation (HOPE) Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031216344690000_R1","doi-asserted-by":"crossref","unstructured":"Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witzum JL: Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. 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