Cited by 1,729Folate and B Vitamins ResearchLipoproteins and Cardiovascular HealthMenopause: Health Impacts and Treatments

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Open access

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators·2006·New England Journal of Medicine

DOI 10.1056/nejmoa060900

Open this paper in CoChat — free account Open PDF

Abstract

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.).

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1056/nejmoa060900

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216
Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction
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
Lowering Homocysteine in Patients With Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death: The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial
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
Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials
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

Flagged first, then by citations

Show all 20 references

Sorted by citations

Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis
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
Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
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
2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association
Kleindorfer, D. O., Towfighi, A., Chaturvedi, S., Cockroft, K. M., Gutierrez, J., Lombardi-Hill, D., Kamel, H., Kernan, W. N., Kittner, S. J., Leira, E. C., et al. (2021) · Stroke · doi:10.1161/str.0000000000000375 · Cited by 3,237
Mechanisms of Diabetic Complications
Forbes, J. M., & Cooper, M. E. (2013) · Physiological Reviews · doi:10.1152/physrev.00045.2011 · Cited by 2,890
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)
Norgren, L., Hiatt, W. R., Dormandy, J., Nehler, M. R., Harris, K. A., & Fowkes, F. G. R. (2006) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2006.09.024 · Cited by 2,877
Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.176158 · Cited by 2,705
Guidelines for the Primary Prevention of Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Meschia, J. F., Bushnell, C., Boden-Albala, B., Braun, L. T., Bravata, D. M., Chaturvedi, S., Creager, M. A., Eckel, R. H., Elkind, M. S. V., Fornage, M., et al. (2014) · Stroke · doi:10.1161/str.0000000000000046 · Cited by 2,650
2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: Executive Summary
Fihn, S. D., Gardin, J. M., Abrams, J., Berra, K., Blankenship, J. C., Dallas, A. P., Douglas, P. S., Foody, J. M., Gerber, T. C., Hinderliter, A. L., et al. (2012) · Circulation · doi:10.1161/cir.0b013e3182776f83 · Cited by 2,419
Vitamin D Deficiency and Risk of Cardiovascular Disease
Wang, T. J., Pencina, M. J., Booth, S. L., Jacques, P. F., Ingelsson, E., Lanier, K. J., Benjamin, E. J., D’Agostino, R. B., Wolf, M. S., & Vasan, R. S. (2008) · Circulation · doi:10.1161/circulationaha.107.706127 · Cited by 2,423
One-Carbon Metabolism in Health and Disease
Ducker, G. S., & Rabinowitz, J. D. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.009 · Cited by 2,239
“…lowering homocysteine levels, folate and cobalamin supplementation do not reduce the incidence of cardiovascular events in the general population, arguing against high homocysteine levels directly causing cardiovascular disease (Bazzano et al., 2006; Lonn et al., 2006; Zhou et al., 2011).”
Background
2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease
Gerhard-Herman, M. D., Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.11.007 · Cited by 1,941
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.181940 · Cited by 1,972
2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease
Fihn, S. D., Gardin, J. M., Abrams, J., Berra, K., Blankenship, J. C., Dallas, A. P., Douglas, P. S., Foody, J. M., Gerber, T. C., Hinderliter, A. L., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.07.013 · Cited by 1,583
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.02.013 · Cited by 1,506
Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack
Furie, K. L., Kasner, S. E., Adams, R. J., Albers, G. W., Bush, R. L., Fagan, S. C., Halperin, J. L., Johnston, S. C., Katzan, I. L., Kernan, W. N., et al. (2010) · Stroke · doi:10.1161/str.0b013e3181f7d043 · Cited by 1,497
Statistics in Medicine — Reporting of Subgroup Analyses in Clinical Trials
Wang, R., Lagakos, S. W., Ware, J. H., Hunter, D. J., & Drazen, J. M. (2007) · New England Journal of Medicine · doi:10.1056/nejmsr077003 · Cited by 1,445
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
Guidelines for the Primary Prevention of Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association
Goldstein, L. B., Bushnell, C. D., Adams, R. J., Appel, L. J., Braun, L. T., Chaturvedi, S., Creager, M. A., Culebras, A., Eckel, R. H., Hart, R. G., et al. (2011) · Stroke · doi:10.1161/str.0b013e3181fcb238 · Cited by 1,306
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: Executive Summary
Amsterdam, E. A., WENGER, N. K., Brindis, R. G., Casey, D. E., Ganiats, T. G., Holmes, D. R., Jaffe, A. S., Jneid, H. M., Kelly, R. F., Kontos, M. C., et al. (2014) · Circulation · doi:10.1161/cir.0000000000000133 · Cited by 1,266
American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease
Jellinger, P. S., Handelsman, Y., Rosenblit, P. D., Bloomgarden, Z. T., Fonseca, V. A., Garber, A. J., Grunberger, G., Guerin, C. K., Bell, D. S. H., Mechanick, J. I., et al. (2017) · Endocrine Practice · doi:10.4158/ep171764.appgl · Cited by 1,094
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
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) · Circulation · doi:10.1161/cir.0000000000000134 · Cited by 1,059
2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Gerhard‐Herman, M. D., Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000470 · Cited by 1,093
Sex/Gender Differences in Cardiovascular Disease Prevention: What a Difference a Decade Makes
Mosca, L., Barrett-Connor, E., & Kass Wenger, N. (2011) · Circulation · doi:10.1161/circulationaha.110.968792 · Cited by 1,045
Risk Factors for Early Myocardial Infarction in South Asians Compared With Individuals in Other Countries
Joshi, P., Islam, S., Pais, P. S., Reddy, S., Prabhakaran, D., Kazmi, K. A., Pandey, M. R., Haque, S., Mendis, S., Rangarajan, S., et al. (2007) · JAMA · doi:10.1001/jama.297.3.286 · Cited by 1,038
2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Gerhard‐Herman, M. D., Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., et al. (2016) · Circulation · doi:10.1161/cir.0000000000000471 · Cited by 1,048
2012 ACCF/AHA Focused Update Incorporated Into the ACCF/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.01.014 · Cited by 968
Folic Acid for the Prevention of Colorectal Adenomas: A Randomized Clinical Trial
Cole, B. F., Baron, J. A., Sandler, R. S., Haile, R. W., Ahnen, D. J., Bresalier, R. S., McKeown-Eyssen, G., Summers, R. W., Rothstein, R. I., Burke, C. A., et al. (2007) · JAMA · doi:10.1001/jama.297.21.2351 · Cited by 929
2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons
Fihn, S. D., Gardin, J. M., Abrams, J., Berra, K., Blankenship, J. C., Dallas, A. P., Douglas, P. S., Foody, J. M., Gerber, T. C., Hinderliter, A. L., et al. (2012) · Circulation · doi:10.1161/cir.0b013e318277d6a0 · Cited by 845
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes: Executive Summary
Amsterdam, E. A., WENGER, N. K., Brindis, R. G., Casey, D. E., Ganiats, T. G., Holmes, D. R., Jaffe, A. S., Jneid, H. M., Kelly, R. F., Kontos, M. C., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.09.016 · Cited by 782
2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations
Genest, J. J., McPherson, R., Frohlich, J. J., Anderson, T. J., Campbell, N. R. C., Carpentier, A. C., Couture, P., Dufour, R., Fodor, G. J., Francis, G. A., et al. (2009) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(09)70715-9 · Cited by 765
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women: 2007 Update
Mosca, L. J., Banka, C. L., Benjamin, E. J., Berra, K. A., Bushnell, C., Dolor, R. J., Ganiats, T. G., Gomes, A. S., Gornik, H. L., Gracia, C., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.02.020 · Cited by 753
Guidelines for the Primary Prevention of Stroke A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
Goldstein, L. B., Bushnell, C., Adams, R. J., Appel, L. J., Braun, L. T., Chaturvedi, S., Creager, M. A., Culebras, A., Eckel, R. H., Hart, R. G., et al. (2011) · Stroke · Cited by 745
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Gornik, H. L., Aronow, H. D., Goodney, P. P., Arya, S., Brewster, L. P., Byrd, L., Chandra, V., Drachman, D. E., Eaves, J. M., Ehrman, J. K., et al. (2024) · Circulation · doi:10.1161/cir.0000000000001251 · Cited by 771
Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China
Huo, Y., Li, J., Qin, X., Huang, Y., Wang, X., Gottesman, R. F., Tang, G., Wang, B., Chen, D., He, M., et al. (2015) · JAMA · doi:10.1001/jama.2015.2274 · Cited by 739
Food synergy: an operational concept for understanding nutrition
Jacobs, D. R., Gross, M. D., & Tapsell, L. C. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.26736b · Cited by 665
Joint British Societies' consensus recommendations for the prevention of cardiovascular disease (JBS3)
JBS3 Board (2014) · Heart · doi:10.1136/heartjnl-2014-305693 · Cited by 608
Is folic acid good for everyone?
Smith, A. D., Kim, Y., & Refsum, H. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.3.517 · Cited by 617
Efficacy of folic acid supplementation in stroke prevention: a meta-analysis
Wang, X., Qin, X., Demirtaş, H., Li, J., Mao, G., Huo, Y., Sun, N., Liu, L., & Xu, X. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60854-x · Cited by 592
2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary
Gerhard‐Herman, M. D., Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., et al. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.11.008 · Cited by 581
American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis
Jellinger, P. S., Smith, D. A., Mehta, A., Ganda, O. P., Handelsman, Y., Rodbard, H. W., Shepherd, M. D., & Seibel, J. A. (2012) · Endocrine Practice · doi:10.4158/ep.18.s1.1 · Cited by 533
Vitamin B12 in Health and Disease
O’Leary, F., & Samman, S. (2010) · Nutrients · doi:10.3390/nu2030299 · Cited by 524
2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Wright, R. S., Anderson, J. L., Adams, C. D., Bridges, C. R., Casey, D. E., Ettinger, S. M., Fesmire, F. M., Ganiats, T. G., Jneid, H. M., Lincoff, A. M., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.02.011 · Cited by 513
Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease
Albert, C. M., Cook, N. R., Gaziano, J. M., Zaharris, E., MacFadyen, J. G., Danielson, E., Buring, J. E., & Manson, J. E. (2008) · JAMA · doi:10.1001/jama.299.17.2027 · Cited by 509
Homocysteine lowering interventions for preventing cardiovascular events
Martí-Carvajal, A. J., Solà, I., Lathyris, D., & Salanti, G. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006612.pub2 · Cited by 520
Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease, Cancer, and Cause-Specific Mortality<subtitle>Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals</subtitle><alt-title>Effects of Lowering Homocysteine Levels</alt-title>
(2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.348 · Cited by 498
Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial
(2009) · The Lancet · doi:10.1016/s0140-6736(09)60611-5 · Cited by 474
Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials
Myung, S.-K., Ju, W., Cho, B., Oh, S.-W., Park, S. M., Koo, B.-K., Park, B.-J., & for the Korean Meta-Analysis (KORMA) Study Group (2013) · BMJ · doi:10.1136/bmj.f10 · Cited by 467
The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia
Fruchart, J.-C., Sacks, F., Hermans, M. P., Assmann, G., Brown, W. V., Ceska, R., Chapman, M. J., Dodson, P. M., Fioretto, P., Ginsberg, H. N., et al. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.10.002 · Cited by 463
Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets?
Rochette, L., Lorin, J., Zeller, M., Guilland, J.-C., Lorgis, L., Cottin, Y., & Vergely, C. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.07.004 · Cited by 456
“Combined daily administration of folic acid, vitamin B6, and vitamin B12 for five years had no beneficial effects on major vascular events in a high-risk population with vascular disease (Lonn et al., 2006).”
Background
The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism
Lever, M., & Slow, S. (2010) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2010.03.009 · Cited by 479
Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial
Galan, P., Kesse-Guyot, E., Czernichow, S., Briancon, S., Blacher, J., Hercberg, S., & for the SU.FOL.OM3 Collaborative Group (2010) · BMJ · doi:10.1136/bmj.c6273 · Cited by 457
Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association
Volgman, A. S., Palaniappan, L. S., Aggarwal, N. T., Gupta, M., Khandelwal, A., Krishnan, A. V., Lichtman, J. H., Mehta, L. S., Patel, H. N., Shah, K. S., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000580 · Cited by 552
Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease
Jamison, R. L., Hartigan, P. M., Kaufman, J. S., Goldfarb, D. S., Warren, S. R., Guarino, P., Gaziano, J. M., & for the RED-CABG Steering Committee and Investigators (2007) · JAMA · doi:10.1001/jama.298.10.1163 · Cited by 454
2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease
Brott, T. G., Halperin, J. L., Abbara, S., Bacharach, J. M., Barr, J. D., Bush, R. L., Cates, C. U., Creager, M. A., Fowler, S. A., Friday, G. H., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.11.006 · Cited by 451
Nutrition, physical activity, and cardiovascular disease: An update
IGNARRO, L., Balestrieri, M. L., & Claudio Napoli, A. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.06.030 · Cited by 454
Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases
Bazzano, L., Reynolds, K., Holder, K. N., & He, J. (2006) · JAMA · doi:10.1001/jama.296.22.2720 · Cited by 426
Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B12
Ebbing, M. (2009) · JAMA · doi:10.1001/jama.2009.1622 · Cited by 428
Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease
Román, G. C., Jackson, R. E., Gadhia, R. R., Roman, A., & Reis, J. J. (2019) · Revue Neurologique · doi:10.1016/j.neurol.2019.08.005 · Cited by 447
Food, Not Nutrients, Is the Fundamental Unit in Nutrition
Jacobs, D. R., & Tapsell, L. C. (2008) · Nutrition Reviews · doi:10.1111/j.1753-4887.2007.tb00269.x · Cited by 436
Folate and colorectal cancer: An evidence‐based critical review
Kim, Y. (2007) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200600191 · Cited by 422
Mortality and Cardiovascular Events in Patients Treated With Homocysteine-Lowering B Vitamins After Coronary Angiography
Ebbing, M., Bleie, Ø., Ueland, P. M., Nordrehaug, J. E., Nilsen, D. W. T., Vollset, S. E., Refsum, H., Pedersen, E. R., & Nygard, O. K. (2008) · JAMA · doi:10.1001/jama.300.7.795 · Cited by 408
Safety considerations with fibrate therapy
Davidson, M. H., Armani, A., McKenney, J. M., & Jacobson, T. A. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.11.016 · Cited by 408
Genetics of ischaemic stroke
Dichgans, M. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70028-5 · Cited by 400
Homocysteine Level and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis
Humphrey, L. L., Fu, R. F., Rogers, K. R., Freeman, M., & Helfand, M. (2008) · Mayo Clinic Proceedings · doi:10.4065/83.11.1203 · Cited by 399
Aspirin and Folic Acid for the Prevention of Recurrent Colorectal Adenomas
Logan, R. F., Grainge, M. J., Shepherd, V., Armitage, N. C. M., & Muir, K. R. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.014 · Cited by 392
The metabolism and significance of homocysteine in nutrition and health
Kumar, A., Palfrey, H. A., Pathak, R., Kadowitz, P. J., Gettys, T. W., & Murthy, S. N. (2017) · Nutrition & Metabolism · doi:10.1186/s12986-017-0233-z · Cited by 399
5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production in Human Vessels: Effects on Vascular Tetrahydrobiopterin Availability and Endothelial Nitric Oxide Synthase Coupling
Antoniades, C., Shirodaria, C., Warrick, N., Cai, S., de Bono, J., Lee, J., Leeson, P., Neubauer, S., Ratnatunga, C., Pillai, R., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.612325 · Cited by 365
Micronutrients in Health and Disease
Shenkin, A. (2006) · Postgraduate Medical Journal · doi:10.1136/pgmj.2006.047670 · Cited by 357
Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000238352.25222.5e · Cited by 345
Allograft Vasculopathy Versus Atherosclerosis
Rahmani, M., Cruz, R. P., Granville, D. J., & McManus, B. M. (2006) · Circulation Research · doi:10.1161/01.res.0000246086.93555.f3 · Cited by 346
2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2011) · Circulation · doi:10.1161/cir.0b013e318212bb8b · Cited by 352
Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study
de Ruijter, W., Westendorp, R. G. J., Assendelft, W. J. J., den Elzen, W. P. J., de Craen, A. J. M., le Cessie, S., & Gussekloo, J. (2009) · BMJ · doi:10.1136/bmj.a3083 · Cited by 339
Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials
Holmes, M. V., Newcombe, P. J., Hubacek, J. A., Sofat, R., Ricketts, S. L., Cooper, J. A., Breteler, M. M. B., Bautista, L. E., Sharma, P. K., Whittaker, J. C., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60872-6 · Cited by 331
Effects of Homocysteine-Lowering With Folic Acid Plus Vitamin B 12 vs Placebo on Mortality and Major Morbidity in Myocardial Infarction Survivors: A Randomized Trial
(2010) · JAMA · doi:10.1001/jama.2010.840 · Cited by 327
The Evidence for Dietary Prevention and Treatment of Cardiovascular Disease
Horn, L. V., McCoin, M., Kris‐Etherton, P. M., Burke, F., Carson, J. A. S., Champagne, C. M., Karmally, W., & Sikand, G. (2008) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2007.10.050 · Cited by 325
Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals
Vollset, S. E., Clarke, R., Lewington, S., Ebbing, M., Halsey, J., Lonn, E., Armitage, J., Manson, J. E., Hankey, G. J., Spence, J. D., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)62001-7 · Cited by 332
Vitamin status in morbidly obese patients: a cross-sectional study
Aasheim, E. T., Hofsø, D., Hjelmesæth, J., Birkeland, K. I., & Bøhmer, T. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.2.362 · Cited by 316
B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial
(2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70187-3 · Cited by 312
The Treatment of Hyperhomocysteinemia
Maron, B. A., & Loscalzo, J. (2008) · Annual Review of Medicine · doi:10.1146/annurev.med.60.041807.123308 · Cited by 312
Canadian Cardiovascular Society position statement – Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease
McPherson, R., Frohlich, J. J., Fodor, G. J., & Genest, J. J. (2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70310-5 · Cited by 306
Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy
House, A. A., Eliasziw, M., Cattran, D. C., Churchill, D. N., Oliver, M. J., Fine, A., Dresser, G. K., & Spence, J. D. (2010) · JAMA · doi:10.1001/jama.2010.490 · Cited by 303
Homocysteine Modification in Protein Structure/Function and Human Disease
Jakubowski, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00003.2018 · Cited by 310
Trends in blood folate and vitamin B-12 concentrations in the United States, 1988–2004
Pfeiffer, C. M., Johnson, C. L., Jain, R. B., Yetley, E. A., Picciano, M. F., Rader, J. I., Fisher, K. D., Mulinare, J., & Osterloh, J. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.3.718 · Cited by 304
Homocysteine Trials — Clear Outcomes for Complex Reasons
Loscalzo, J. (2006) · New England Journal of Medicine · doi:10.1056/nejme068060 · Cited by 296
Vitamin B6: A Long Known Compound of Surprising Complexity
Mooney, S., Leuendorf, J. E., Hendrickson, C., & Hellmann, H. A. (2009) · Molecules · doi:10.3390/molecules14010329 · Cited by 299
The burden of cardiovascular disease in the Indian subcontinent.
Goyal, A., & Yusuf, S. (2006) · PubMed · Cited by 286
Homocysteine and cardiovascular disease: a review of the evidence
Wierzbicki, A. S. (2007) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2007.033 · Cited by 290
2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease
Gornik, H. L., Aronow, H. D., Goodney, P. P., Arya, S., Brewster, L. P., Byrd, L., Chandra, V., Drachman, D. E., Eaves, J. M., Ehrman, J. K., et al. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.02.013 · Cited by 294
ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction—Executive Summary
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.02.028 · Cited by 282
Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial
den Heijer, M., Willems, H. P. J., Blom, H. J., Gerrits, W. B. J., Cattaneo, M., Eichinger, S., Rosendaal, F. R., & Bos, G. M. J. (2006) · Blood · doi:10.1182/blood-2006-04-014654 · Cited by 276
Homocysteine-lowering interventions for preventing cardiovascular events
Martí-Carvajal, A. J., Solà, I., Lathyris, D., & Dayer, M. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006612.pub5 · Cited by 295
Cardiovascular disease prevention with a multidrug regimen in the developing world: a cost-effectiveness analysis
Gaziano, T. A., Opie, L. H., & Weinstein, M. C. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69252-0 · Cited by 273
2012 ACCF/AHA Focused Update Incorporated Into the ACCF/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E., Chavey, W. E., Fesmire, F. M., Hochman, J. S., Levin, T. N., et al. (2013) · Circulation · doi:10.1161/cir.0b013e31828478ac · Cited by 275
Polypill with or without Aspirin in Persons without Cardiovascular Disease
Yusuf, S., Joseph, P. G., Dans, A., Gao, P., Teo, K. K., Xavier, D., López-Jaramillo, P. A., Yusoff, K., Santoso, A., Gamra, H., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2028220 · Cited by 273
Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta‐Analysis of Randomized Controlled Trials
Li, Y., Huang, T., Zheng, Y., Muka, T., Troup, J., & Hu, F. B. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003768 · Cited by 268
2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Artery Disease: Executive Summary
Gerhard‐Herman, M. D., Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., et al. (2017) · Vascular Medicine · doi:10.1177/1358863x17701592 · Cited by 271
The Homocysteine Hypothesis of Depression
Folstein, M. F., Liu, T., Peter, I., Buel, J., Arsenault, L. N., Scott, T. M., & Qiu, W. W. Q. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.6.861 · Cited by 271

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
DOI: 10.1056/nejmoa060900
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks