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Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease
Open accessAbstract
BACKGROUND: In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease. METHODS: We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. RESULTS: Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49). CONCLUSIONS: Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).
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Cites
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216
Antman, E. M., Bassand, J., Klein, W. W., Ohman, M. E., Sendón, J. L. L., Rydén, L., Simoons, M. L., & Tendera, M. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00804-4 · Cited by 4,824
A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease
Boushey, C. J. (1995) · JAMA · doi:10.1001/jama.1995.03530130055028 · Cited by 3,708
Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis
Homocysteine Studies Collaboration (2002) · JAMA · doi:10.1001/jama.288.16.2015 · Cited by 2,059
Homocysteine and Atherothrombosis
Welch, G. N., & Loscalzo, J. (1998) · New England Journal of Medicine · doi:10.1056/nejm199804093381507 · Cited by 1,997
Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Wald, D. S., Law, M., & Morris, J. K. (2002) · BMJ · doi:10.1136/bmj.325.7374.1202 · Cited by 1,945
Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction
Bønaa, K. H., Njølstad, I., Ueland, P. M., Schirmer, H., Tverdal, A., Steigen, T., Wang, H., Nordrehaug, J. E., Arnesen, E., & Rasmussen, K. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055227 · Cited by 1,442
Toole, J. F., Malinow, M. R., Chambless, L. E., Spence, J. D., Pettigrew, L. C., Howard, V. J., Sides, E. G., Wang, C.-H., & Stampfer, M. (2004) · JAMA · doi:10.1001/jama.291.5.565 · Cited by 1,391
Vivekananthan, D. P., Penn, M. S., Sapp, S. K., Hsu, A., & Topol, E. J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13637-9 · Cited by 1,083
MTHFR 677C→T Polymorphism and Risk of Coronary Heart Disease
Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J., & Schouten, E. G. (2002) · JAMA · doi:10.1001/jama.288.16.2023 · Cited by 932
Homocyst(e)ine and Cardiovascular Disease: A Critical Review of the Epidemiologic Evidence
Eikelboom, J. W., Lonn, E., Genest, J. J., Hankey, G. J., & Yusuf, S. (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-131-5-199909070-00008 · Cited by 908
Boushey, C. J. (1995) · JAMA · doi:10.1001/jama.274.13.1049 · Cited by 771
Harker, L. A., Slichter, S. J., Scott, C. R., & Ross, R. (1974) · New England Journal of Medicine · doi:10.1056/nejm197409122911101 · Cited by 667
Malinow, M. R., Bostom, A. G., & Krauss, R. M. (1999) · Circulation · doi:10.1161/01.cir.99.1.178 · Cited by 586
Homocysteine Lowering Trialists’ Collaboration (2005) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/82.4.806 · Cited by 454
Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons.
Harker, L. A., Harlan, J. M., & Ross, R. (1983) · Circulation Research · doi:10.1161/01.res.53.6.731 · Cited by 245
B-Vitamin Treatment Trialists' Collaboration (2006) · American Heart Journal · doi:10.1016/j.ahj.2005.04.025 · Cited by 156
Secondary prevention with folic acid: effects on clinical outcomes
Liem, A. H., Reynierse-Buitenwerf, G. H., Zwinderman, A. H., Jukema, J. W., & van Veldhuisen, D. J. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00485-6 · Cited by 150
Lonn, E. (2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70238-0 · Cited by 59
Alpert, J., Antman, E., Apple, F., Armstrong, P. W., Bassand, J., de Luna, A. D., Beller, G., Breithardt, G., Chaitman, B., Clemmensen, P., et al. (2000) · European Heart Journal · doi:10.1053/euhj.2000.2305 · Cited by 37
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Zhang, Q., Wang, C., Zheng, M., Li, Y., Li, J., Zhang, L., Shang, X., & Yan, C. (2014) · Cerebrovascular Diseases · doi:10.1159/000369778 · Cited by 11,609
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)
Norgren, L., Hiatt, W. R., Dormandy, J. A., Nehler, M. R., Harris, K. A., & Fowkes, F. G. R. (2007) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2006.12.037 · Cited by 8,191
Kernan, W. N., Ovbiagele, B., Black, H. R., Bravata, D. M., Chimowitz, M. I., Ezekowitz, M. D., Fang, M. C., Fisher, M., Furie, K. L., Heck, D. V., et al. (2014) · Stroke · doi:10.1161/str.0000000000000024 · Cited by 5,170
Progress and challenges in translating the biology of atherosclerosis
Libby, P., Ridker, P. M., & Hansson, G. K. (2011) · Nature · doi:10.1038/nature10146 · Cited by 4,010
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes
Amsterdam, E. A., Wenger, N. K., Brindis, R. G., Casey, D. E., Ganiats, T. G., Holmes, D. R., Jaffe, A. S., Jneid, H., Kelly, R. F., Kontos, M. C., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.09.017 · Cited by 3,595
Metadata
- Authors
- The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
- Affiliations
- Hamilton General Hospital (CA)
- Corresponding author
- The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-04-13
- Volume
- 354
- Issue
- 15
- Pages
- 1567-1577
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2109544293
- Cited by
- 1,729
- References
- 20
- Citations by year
- 2026: 43 · 2025: 46 · 2024: 33 · 2023: 30 · 2022: 43 · 2021: 37 · 2020: 52 · 2019: 46 · 2018: 46 · 2017: 70 · 2016: 81 · 2015: 77 · 2014: 84 · 2013: 85 · 2012: 104
- FWCI
- 136.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- Massachusetts Medical Society
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- homocysteine lowering, folic acid, vitamin B6, vitamin B12, vascular disease, cardiovascular events, stroke, myocardial infarction, cardiovascular mortality, unstable angina, diabetes mellitus, older adults
- MeSH terms
- Aged, Cardiovascular Diseases, Diabetes Mellitus, Double-Blind Method, Drug Therapy, Combination, Female, Folic Acid, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction, Risk Factors, Vascular Diseases, Vitamin B 12, Hyperhomocysteinemia, Stroke, Vitamin B 6
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