This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (38)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Neurology  • Stroke  • Cardiovascular System  • Women's Health  • Women's Health, Other  • Randomized Controlled Trial  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic  Social Bookmarking   What's this?

Results From the Women's Antioxidant Cardiovascular Study

Nancy R. Cook, ScD; Christine M. Albert, MD; J. Michael Gaziano, MD; Elaine Zaharris, BA; Jean MacFadyen, BA; Eleanor Danielson, MIA; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH

Arch Intern Med. 2007;167(15):1610-1618.

Background  Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD.

Methods  The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005.

Results  A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03).

Conclusion  There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.

Trial Registration  clinicaltrials.gov Identifier: NCT00000541

Author Affiliations: Divisions of Preventive Medicine (Drs Cook, Albert, Gaziano, Buring, and Manson and Mss Zaharris, MacFadyen, and Danielson), Cardiovascular Medicine (Drs Albert, Gaziano, and Buring), and Aging (Drs Gaziano and Buring), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard School of Public Health, Boston (Drs Cook, Buring, and Manson); Veterans Affairs Boston Healthcare System (Dr Gaziano); and Department of Ambulatory Care and Prevention, Harvard Medical School, Boston (Dr Buring).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Clinical Trials of Antioxidant Supplementation in the Prevention of Cardiovascular Events
Niki Katsiki and Christos Manes
Arch Intern Med. 2008;168(7):773.
EXTRACT | FULL TEXT  

Clinical Trials of Antioxidant Supplementation in the Prevention of Cardiovascular Events—Reply
Nancy R. Cook, Christine M. Albert, JoAnn E. Manson, and for the WACS Investigator Group
Arch Intern Med. 2008;168(7):773-774.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Use of Supplements of Multivitamins, Vitamin C, and Vitamin E in Relation to Mortality
Pocobelli et al.
Am J Epidemiol 2009;170:472-483.
ABSTRACT | FULL TEXT  

Effects of vitamins C and E and {beta}-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial
Song et al.
Am. J. Clin. Nutr. 2009;90:429-437.
ABSTRACT | FULL TEXT  

Effect of Homocysteine-Lowering Treatment With Folic Acid and B Vitamins on Risk of Type 2 Diabetes in Women: A Randomized, Controlled Trial
Song et al.
Diabetes 2009;58:1921-1928.
ABSTRACT | FULL TEXT  

Multivitamin Supplements, Ageing, and Loss of Vision: Seeing Through the Shadows
Phillips and Higginbotham
Arch Intern Med 2009;169:1180-1182.
FULL TEXT  

Vitamin E, Vitamin C, Beta Carotene, and Cognitive Function Among Women With or at Risk of Cardiovascular Disease: The Women's Antioxidant and Cardiovascular Study
Kang et al.
Circulation 2009;119:2772-2780.
ABSTRACT | FULL TEXT  

Does reversal of oxidative stress and inflammation provide vascular protection?
Koh et al.
Cardiovasc Res 2009;81:649-659.
ABSTRACT | FULL TEXT  

Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women: The Women's Antioxidant and Folic Acid Cardiovascular Study
Christen et al.
Arch Intern Med 2009;169:335-341.
ABSTRACT | FULL TEXT  

Vitamin E supplementation: what's the harm in that?
Miller and Guallar
Clin Trials 2009;6:47-49.
 

Nutrition and Heart Failure: Impact of Drug Therapies and Management Strategies
Dunn et al.
Nutr Clin Pract 2009;24:60-75.
ABSTRACT | FULL TEXT  

Vitamin Supplements and Cancer Prevention: Where Do Randomized Controlled Trials Stand?
Albanes
JNCI J Natl Cancer Inst 2009;101:2-4.
FULL TEXT  

Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial
Lin et al.
JNCI J Natl Cancer Inst 2009;101:14-23.
ABSTRACT | FULL TEXT  

Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians' Health Study II Randomized Controlled Trial
Sesso et al.
JAMA 2008;300:2123-2133.
ABSTRACT | FULL TEXT  

Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Cancer Risk in Women: A Randomized Trial
Zhang et al.
JAMA 2008;300:2012-2021.
ABSTRACT | FULL TEXT  

Lifestyle and Risk of Cardiovascular Disease and Type 2 Diabetes in Women: A Review of the Epidemiologic Evidence
Bassuk and Manson
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2008;2:191-213.
ABSTRACT  

Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease: A Randomized Trial
Albert et al.
JAMA 2008;299:2027-2036.
ABSTRACT | FULL TEXT  

Clinical Trials of Antioxidant Supplementation in the Prevention of Cardiovascular Events
Katsiki and Manes
Arch Intern Med 2008;168:773-773.
FULL TEXT  

Clinical Trials of Antioxidant Supplementation in the Prevention of Cardiovascular Events--Reply
Cook et al.
Arch Intern Med 2008;168:773-774.
FULL TEXT  

Vitamins C and E and Beta Carotene Do Not Prevent Cardiovascular Events in Women
JWatch General 2007;2007:1-1.
FULL TEXT