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

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Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

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

DOI 10.1056/nejmoa060900

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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.).

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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

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Homocysteine Is Associated With Future Venous Thromboembolism in 2 Prospective Cohorts of Women
Aday, A. W., Duran, E. K., Denburgh, M. V., Kim, E., Christen, W. G., Manson, J. E., Ridker, P. M., & Pradhan, A. D. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316397 · Cited by 37
2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.
Ueng, K., Chiang, C., Chao, T., Wu, Y., Lee, W.-L., Li, Y., Ting, K.-H., Su, C.-H., Lin, H., Su, T., et al. (2023) · PubMed Central · doi:10.6515/acs.202301_39(1).20221103a · Cited by 34
Therapeutical approach to plasma homocysteine and cardiovascular risk reduction
Ciaccio, M. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s1807 · Cited by 34
Mass spectrometry evidence for formation of estrogen–homocysteine conjugates: Estrogens can regulate homocysteine levels
Gaikwad, N. W. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.041 · Cited by 35
Plasma total cysteine and total homocysteine and risk of myocardial infarction in women: A prospective study
Page, J. H., Ma, J., Chiuve, S. E., Stampfer, M. J., Selhub, J., Manson, J. E., & Rimm, E. B. (2010) · American Heart Journal · doi:10.1016/j.ahj.2009.12.037 · Cited by 34
A nutrient‐dense, high‐fiber, fruit‐based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2‐wk trial
Mietus‐Snyder, M., Shigenaga, M. K., Suh, J. H., Shenvi, S. V., Lal, A., McHugh, T. H., Olson, D., Lilienstein, J., Krauss, R. M., Gildengoren, G. L., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-201558 · Cited by 34
Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation
Guéant‐Rodriguez, R., Spada, R. S., Pooya, S., Jeannesson, É., Garcia, M. A. M., Anello, G., Bosco, P., Elia, M., Romano, A. G., Alberto, J., et al. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.03.047 · Cited by 36
“However the implication of Hcy in cardiovascular risk became a matter of debate when interventional studies with vitamin B in populations with cardiovascular disease at baseline showed no benefit on secondary adverse outcomes, despite the efficacy of vitamins B in lowering its blood level [2,3,29,30].”
Background
Effects of Folic Acid Supplementation on Serum Folate and Plasma Homocysteine Concentrations in Older Adults: A Dose-Response Trial
Anderson, C. A. M., Jee, S. H., Charleston, J. B., Narrett, M., & Appel, L. J. (2010) · American Journal of Epidemiology · doi:10.1093/aje/kwq197 · Cited by 34
High-Density Lipoprotein-Associated Paraoxonase-1 Activity for Prediction of Adverse Outcomes in Outpatients with Chronic Heart Failure
Hammadah, M., Kalogeropoulos, A. P., Georgiopoulou, V. V., Weber, M. E., Wu, Y., Hazen, S. L., Butler, J., & Tang, W. H. W. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.777 · Cited by 33
Cardiovascular Disease in Patients with Chronic Kidney Disease
Weiner, D. E., & Sarnak, M. J. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0987-2.00010-8 · Cited by 35
Thrombosis in Infants and Children
Schneppenheim, R., & Greiner, J. (2006) · Hematology · doi:10.1182/asheducation-2006.1.86 · Cited by 33
Should folic acid fortification be mandatory? No
Hubner, R. A., Houlston, R. S., & Muir, K. R. (2007) · BMJ · doi:10.1136/bmj.39232.496227.47 · Cited by 34
Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide
Zhang, N., Zhou, Z., Chi, X., Fan, F., Li, S., Song, Y. M., Zhang, Y., Qin, X., Sun, N., Wang, X., et al. (2024) · Clinical Nutrition · doi:10.1016/j.clnu.2024.05.034 · Cited by 36
Vitamin B and its derivatives for diabetic kidney disease
Raval, A. D., Thakker, D., Rangoonwala, A. N., Gor, D., & Walia, R. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009403.pub2 · Cited by 32
Pyridoxal-5′-phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors
Thériault, O., Poulin, H., Thomas, G. R., Friesen, A. D., Al-Shaqha, W. A., & Chahine, M. (2013) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2013-0404 · Cited by 33
“MC-1, on the other hand, has successfully undergone many safety tests (Hirai et al. 1998; Lonn et al. 2006).”
Background
Analytic Approaches for the Treatment of Hyperhomocysteinemia and Its Impact on Vascular Disease
Kang, S., & Rosenson, R. S. (2018) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-018-6790-1 · Cited by 33
Influence of Nitrous Oxide Anesthesia, B-Vitamins, and MTHFR Gene Polymorphisms on Perioperative Cardiac Events
Nägele, P., Brown, F., Francis, A. M., Scott, M. G., Gage, B. F., & Miller, J. P. (2013) · Anesthesiology · doi:10.1097/aln.0b013e31829761e3 · Cited by 33
Vascular disease in a population-based cohort of individuals hospitalised with coeliac disease
Ludvigsson, J. F., Fairé, U. D., Ekbom, A., & Montgomery, S. (2007) · Heart · doi:10.1136/hrt.2006.097097 · Cited by 33
Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation
Shimano, M., Inden, Y., Tsuji, Y., Kamiya, H., Uchikawa, T., Shibata, R., & Murohara, T. (2008) · EP Europace · doi:10.1093/europace/eun140 · Cited by 33
Homocysteine and cognition – A historical perspective
McCaddon, A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9402 · Cited by 33
Effect of Folic Acid and Betaine Supplementation on Flow-Mediated Dilation: A Randomized, Controlled Study in Healthy Volunteers
Olthof, M. R., Bots, M. L., Katan, M., & Verhoef, P. (2006) · PLoS Clinical Trials · doi:10.1371/journal.pctr.0010010 · Cited by 33
Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study
Basu, A., Jenkins, A. J., Stoner, J. A., Thorpe, S. R., Klein, R. L., Lopes-Virella, M. F., Garvey, W. T., & Lyons, T. J. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.07.001 · Cited by 32
Contribution of Dietary Intakes of Antioxidants to Homocysteine-Induced Low Density Lipoprotein (LDL) Oxidation in Atherosclerotic Patients
Seo, H. S., Oh, H., Park, H. S., Park, M.-Y., Jang, Y., & Lee, M. (2010) · Yonsei Medical Journal · doi:10.3349/ymj.2010.51.4.526 · Cited by 32
Paraoxonases
Martinelli, N., Consoli, L., Girelli, D., Grison, E., Corrocher, R., & Olivieri, O. (2012) · Advances in clinical chemistry · doi:10.1016/b978-0-12-405211-6.00003-6 · Cited by 33
Folate/homocysteine metabolism and lung cancer risk among smokers
Stanisławska‐Sachadyn, A., Borzyszkowska, J., Krzemiński, M., Janowicz, A., Dziadziuszko, R., Jassem, J., Rzyman, W., & Limon, J. (2019) · PLoS ONE · doi:10.1371/journal.pone.0214462 · Cited by 32
Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study: what have we learned from it?
Paraskevas, K. I., Nicolaides, A. N., & Kakkos, S. K. (2020) · Annals of Translational Medicine · doi:10.21037/atm.2020.02.156 · Cited by 32
Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with vitamin B12 deficiency
Chiang, M.-L., Jin, Y., Chiang, C., Wu, Y., Chang, J. Y., & Sun, A. (2019) · Journal of Dental Sciences · doi:10.1016/j.jds.2019.12.002 · Cited by 32
TT Genotype of the Methylenetetrahydrofolate Reductase C677T Polymorphism is an Important Determinant for Homocysteine Levels in Multi-Ethnic Malaysian Ischaemic Stroke Patients
Mohamed, E. H. M., Tan, K. S., Ali, J. M., & Mohamed, Z. (2011) · Annals of the Academy of Medicine Singapore · doi:10.47102/annals-acadmedsg.v40n4p186 · Cited by 32
Nutritional genomics: food industry applications from farm to fork
Brown, L., & OUDERAA, F. V. D. (2007) · British Journal Of Nutrition · doi:10.1017/s0007114507691983 · Cited by 32
Plasma total homocysteine: instigator or indicator of cardiovascular disease?
Moat, S. J. (2008) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1258/acb.2008.008053 · Cited by 31
Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an Ambulatory Elderly Population
Guéant, R.-M., Spada, R. S., Moreno-Garcia, M., Anello, G., Bosco, P., Lagrost, L., Romano, A. G., Elia, M., & Guéant, J. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.11.031 · Cited by 33
The Antiatherogenic Function of HDL Is Impaired in Hyperhomocysteinemic Subjects
Holven, K. B., Aukrust, P., Retterstøl, K., Otterdal, K., Bjerkeli, V., Ose, L., Nenseter, M. S., & Halvorsen, B. L. (2008) · Journal of Nutrition · doi:10.3945/jn.108.090704 · Cited by 33
Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease in a Chinese Han population
Rong, D., Liu, J., Jia, X., AL-Nafisee, D., Jia, S., Sun, G., Li, Y., Lu, W., Li, H., Zhang, H., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.05.006 · Cited by 32
Folic Acid-Based Intervention in Non-ST Elevation Acute Coronary Syndromes
Imasa, M. S. B., Gomez, N. T., & Nevado, J. B. (2009) · Asian Cardiovascular and Thoracic Annals · doi:10.1177/0218492309102494 · Cited by 30
Effectiveness of B Vitamin Supplementation Following Bariatric Surgery: Rapid Increases of Serum Vitamin B12
Moore, C. E., & Sherman, V. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1441-5 · Cited by 31
The role of B vitamins in stroke prevention
Bjørklund, G., Peana, M., Dadar, M., Lozynska, I., Chirumbolo, S., Lysiuk, R., Lenchyk, L. V., Upyr, T. V., & Severin, B. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1885341 · Cited by 30
Problem in the Recent American Heart Association Guideline on Secondary Stroke Prevention: B Vitamins to Lower Homocysteine Do Prevent Stroke
Spence, J. D., & Hankey, G. J. (2022) · Stroke · doi:10.1161/strokeaha.122.038640 · Cited by 32
Odds ratio vs risk ratio in randomized controlled trials
Balasubramanian, H., Ananthan, A., Rao, S. C., & Patole, S. (2015) · Postgraduate Medicine · doi:10.1080/00325481.2015.1022494 · Cited by 32
The Concept of the Polypill in the Prevention of Cardiovascular Disease
Wiley, B. M., & Fuster, V. (2014) · Annals of Global Health · doi:10.1016/j.aogh.2013.12.008 · Cited by 32
Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and vascular dysfunction in hyperhomocysteinemia
Dayal, S., Baumbach, G. L., Arning, E., Bottiglieri, T., Faraci, F. M., & Lentz, S. R. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175732 · Cited by 32
A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke
Jadavji, N. M., Emmerson, J. T., Shanmugalingam, U., MacFarlane, A. J., Willmore, W. G., & Smith, P. D. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.07.014 · Cited by 29
Hematinic deficiencies and hyperhomocysteinemia in gastric parietal cell antibody-positive or gastric and thyroid autoantibodies-negative atrophic glossitis patients
Chiang, C., Chang, J. Y., Wang, Y., Wu, Y., Wu, Y., & Sun, A. (2019) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2019.03.017 · Cited by 30
Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study
Guo, J., Liu, X., Wang, Z., Lu, R., Liu, Y., Zhang, Y., Tian, W., Fang, S., Wang, S., & Yu, B. (2023) · Nutrition Journal · doi:10.1186/s12937-023-00900-6 · Cited by 32
Folate intake and bowel cancer risk
Mathers, J. C. (2009) · Genes & Nutrition · doi:10.1007/s12263-009-0126-5 · Cited by 29
“For example, in the Heart Outcomes Prevention Evaluation (HOPE2) study, where 5,522 people aged [55 years were given 2,500 lg folic acid/day (together with vitamins B6 and B12) for 5 years, there were more cases of both colon and prostate cancer among those randomised to the vitamins but the differences were not stati…”
Method
Stable Ischemic Heart Disease
Padala, S. K., Sidhu, M. S., & Boden, W. E. (2016) · Springer eBooks · doi:10.1007/978-3-642-37393-0_70-2 · Cited by 30
Potential harmful correlation between homocysteine and low-density lipoprotein cholesterol in patients with hypothyroidism
Dong, X., Yao, Z. J., Hu, Y., Yang, N., Gao, X., Xu, Y., & Wang, G. (2016) · Medicine · doi:10.1097/md.0000000000004291 · Cited by 28
Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update on risk factors and life style
Fuentes, B., Gállego, J., Gil-Núñez, A., Morales, A., Purroy, F. F., Roquer, J., Segura, T., Tejada, J., Lago, A. P., Díez‐Tejedor, E., et al. (2012) · Neurología (English Edition) · doi:10.1016/j.nrleng.2011.06.004 · Cited by 30
Homocysteine and Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis
Kubota, Y., Alonso, Á., Heckbert, S. R., Norby, F. L., & Folsom, A. R. (2018) · Heart Lung and Circulation · doi:10.1016/j.hlc.2018.03.007 · Cited by 31
Protective effects of oxymatrine on homocysteine-induced endothelial injury: Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling pathways
Wu, B., Yue, H., Zhou, G. H., Zhu, Y. Y., Wu, T. H., Wen, J. F., Cho, K. W., & Jin, S. N. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172717 · Cited by 30
The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions
Rizzo, G., & Laganà, A. S. (2020) · Biomolecules · doi:10.3390/biom10020219 · Cited by 30
“Hcy represents an independent predictor of CVDs and all-cause mortality for its role in endothelial health and thrombogenesis [37,38].”
Background
The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: A nested case‐referent study
Eklöf, V., Guelpen, B. R. V., Hultdin, J., Johansson, I., Hallmans, G., & Palmqvist, R. (2008) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365510701805431 · Cited by 30
Association of haptoglobin genotype and common cardiovascular risk factors with the amount of iron in atherosclerotic carotid plaques
Lioupis, C., Barbatis, C., Drougou, A., Koliaraki, V., Mamalaki, A., Klonaris, C., Georgopoulos, S., Andrikopoulos, V., & Bastounis, E. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.01.028 · Cited by 30
“FreeHbwithin theplaque ishighly toxic and the incorporated ironacts as anoxidant, promoting a state of increasedoxidative stress andplaque instability [3,7].”
Background
Secondary prevention of stroke
MacDougall, N., Amarasinghe, S., & Muir, K. W. (2009) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.09.77 · Cited by 29
Two Cardiovascular Risk Factors in One? Homocysteine and Its Relation to Glomerular Filtration Rate
Kielstein, J. T., Salpeter, S. R., Buckley, N. S., Cooke, J. P., & Fliser, D. (2008) · Kidney & Blood Pressure Research · doi:10.1159/000142725 · Cited by 29
Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy
Böger, C. A., Stubanus, M., Haak, T., Götz, A., Christ, J. H., Hoffmann, U., Riegger, G. A. J., Krämer, B. K., & for the GENDIAN Study Group (2006) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfl512 · Cited by 30
The Puzzle of Dietary Fat Intake and Risk of Ischemic Stroke: A Brief Review of Epidemiologic Data
He, K., Xu, Y., & Horn, L. V. (2007) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2006.11.010 · Cited by 30
The Role of B-Vitamins in Nutritional Anemia
McNulty, H. (2022) · Nutrition and health · doi:10.1007/978-3-031-14521-6_13 · Cited by 30
Homocysteine, B Vitamins, and Cardiovascular Disease
de Craen, A. J. M., Stott, D. J., & Westendorp, R. G. (2006) · New England Journal of Medicine · doi:10.1056/nejmc061259 · Cited by 30
Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and peripheral artery occlusion disease
Kayacelebi, A. A., Willers, J., Pham, V. V., Hahn, A., Schneider, J. Y., Rothmann, S., Frölich, J. C., & Tsikas, D. (2015) · Amino Acids · doi:10.1007/s00726-015-1915-3 · Cited by 29
“It is noteworthy that treatment of high-risk patients with folic acid, vitamin B12 and vitamin B6 lowered thCys, but did not reduce the cardiovascular risk (Lonn et al. 2006).”
Background
The Effect of Diet on Cardiovascular Disease and Lipid and Lipoprotein Levels
Feingold, K. R. (2021) · Europe PMC (PubMed Central) · Cited by 30
Nutritional Supplements for Older Adults: Review and Recommendations—Part II
Buhr, G. T., & Bales, C. W. (2010) · Journal of Nutrition for the Elderly · doi:10.1080/01639360903586464 · Cited by 29
Association of Serum Homocysteine with Cardiovascular and All‐Cause Mortality in Adults with Diabetes: A Prospective Cohort Study
Lu, J., Chen, K., Chen, W., Liu, C., Jiang, X., Ma, Z., Li, D., Shen, Y., & Tian, H. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/2156483 · Cited by 29
“Some studies have proved that lowering Hcy cannot yield signi ﬁ cant cardiovascular bene ﬁ ts [37].”
Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus
Kiani, A. N., Vogel‐Claussen, J., Arbab‐Zadeh, A., Magder, L. S., Lima, J. A. C., & Petri, M. (2012) · The Journal of Rheumatology · doi:10.3899/jrheum.120197 · Cited by 30
Evidence-based nutrition: Does it differ from evidence-based medicine?
Mann, J. I. (2010) · Annals of Medicine · doi:10.3109/07853890.2010.506449 · Cited by 30
Stable Ischemic Heart Disease
Morrow, D. A., & Boden, W. E. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0398-6.00057-3 · Cited by 28
Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients
Righetti, M. (2007) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2007.335 · Cited by 29
Postgraduate Symposium The MTHFR C677T polymorphism, B-vitamins and blood pressure
Wilson, C. P., McNulty, H., Scott, J. M., Strain, J., & Ward, M. (2009) · Proceedings of The Nutrition Society · doi:10.1017/s0029665109991728 · Cited by 29
Homocysteine-Lowering B Vitamin Therapy in Cardiovascular Prevention—Wrong Again?
Lonn, E. (2008) · JAMA · doi:10.1001/jama.299.17.2086 · Cited by 29
Risk factors for myocardial infarction in very young South Asians
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Le, A., Peng, H., Golinsky, D., Scipio, M. D., Lali, R., & Paré, G. (2024) · Current Atherosclerosis Reports · doi:10.1007/s11883-024-01200-y · Cited by 33
Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin
Cao, L., Zhang, Z., Sun, W., Bai, W., Sun, W., Zhang, Y., Wang, X., Cai, B., Xie, X., Duan, Z., et al. (2014) · Gene · doi:10.1016/j.gene.2014.06.023 · Cited by 28
Anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in burning mouth syndrome patients with or without hyperhomocysteinemia
Chiang, M.-L., Chiang, C., & Sun, A. (2020) · Journal of Dental Sciences · doi:10.1016/j.jds.2020.04.013 · Cited by 28
“Therefore, patients with vitamin B12, folic acid, and/or vitamin B6 deficiencies may have hyperhomocysteinemia.(3,4) Furthermore, the gastric parietal cell antibody (GPCA) can destroy gastric parietal cells, resulting in lack of intrinsic factors and hypochlorhydria.”
Background
Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with or without microcytosis
Jin, Y., Wu, Y., Wu, Y., Chang, J. Y., Chiang, C. P., & Sun, A. (2021) · Journal of Dental Sciences · doi:10.1016/j.jds.2020.12.009 · Cited by 28
Higher S-adenosylhomocysteine and lower ratio of S-adenosylmethionine to S-adenosylhomocysteine were more closely associated with increased risk of subclinical atherosclerosis than homocysteine
Xiao, J., You, Y., Chen, X., Tang, Y., Chen, Y., Liu, Q., Liu, Z., & Ling, W. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.918698 · Cited by 28
General Strategy for Specific Fluorescence Imaging of Homocysteine in Living Cells and In Vivo
Yin, G., Gan, Y., Jiang, H., Yu, T. Y., Liu, M., Zhang, Y., Li, H., Yin, P., & Yao, S. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c00799 · Cited by 28
Homocysteine in the prevention of ischemic heart disease, stroke and venous thromboembolism: therapeutic target or just another distraction?
Lonn, E. (2007) · Current Opinion in Internal Medicine · doi:10.1097/moh.0b013e3282c48bd8 · Cited by 27
Circulating homocysteine and large arterial stiffness and thickness in a population-based sample of middle-aged and elderly men
Nakhai-Pour, H. R., Grobbee, D. E., Bots, M. L., Muller, M., & van der Schouw, Y. T. (2007) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1002247 · Cited by 28
Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C>T and 1298A>C genotypes and haplotypes – evidence for an association with hemorrhagic stroke
Hultdin, J., Guelpen, B. R. V., Winkvist, A., Hallmans, G., Weinehall, L., Stegmayr, B., & Nilsson, T. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.234 · Cited by 28
The impact of obstructive sleep apnea on homocysteine and carotid remodeling in metabolic syndrome
Monneret, D., Tamisier, R., Ducros, V., Garrel, C., Levy, P. A., Baguet, J. P., Faure, P., & Pépin, J. (2011) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2011.12.009 · Cited by 28
Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study
Russo, G. T., Benedetto, A. D., Magazzù, D., Giandalia, A., Giorda, C. B., Ientile, R., Previti, M., Cesare, E. D., & Cucinotta, D. (2009) · Acta Diabetologica · doi:10.1007/s00592-009-0169-5 · Cited by 28
The Role of Vitamin B in Stroke Prevention
Saposnik, G. (2011) · Stroke · doi:10.1161/strokeaha.110.608356 · Cited by 28
High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia
Zittan, E., Preis, M., Asmir, I., Cassel, A., LINDENFELD, N., Alroy, S., Halon, D. A., Lewis, B. S., Shiran, A., Schliamser, J. E., et al. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01189.2006 · Cited by 29
Inhibition of homocysteine-induced endoplasmic reticulum stress and endothelial cell damage by l-serine and glycine
Sim, W.-C., Han, I., Lee, W., Choi, Y., Lee, K.-Y., Kim, D. G., Jung, S.-H., Oh, S., & Lee, B. (2016) · Toxicology in Vitro · doi:10.1016/j.tiv.2016.04.004 · Cited by 28
“The Heart Outcomes Prevention Evaluation 2 Investigators report also showed that reducing plasma homocysteine levels in patients with vascular disease or diabetes did not reduce the risk of major cardiovascular events (Lonn et al., 2006).”
Non-ST Elevation Acute Coronary Syndromes: A Comprehensive Review
Bob‐Manuel, T., Ifedili, I., Reed, G. L., Ibebuogu, U. N., & Khouzam, R. N. (2017) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2017.04.006 · Cited by 33
Untitled work
(2009) · PubMed Central
Treatment - Therapeutic Lifestyle Modification
Teramoto, T., Sasaki, J., Ueshima, H., Egusa, G., Kinoshita, M., Shimamoto, K., Daida, H., Biro, S., Hirobe, K., Funahashi, T., et al. (2008) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.e601 · Cited by 26
Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis
B-Vitamin Treatment Trialists' Collaboration (2007) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2007.346 · Cited by 28
Role of hyperhomocysteinemia in atherosclerosis: from bench to bedside
Tian, W., Ju, J., Guan, B., Wang, T., Zhang, J., Song, L., & Xu, H. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2457527 · Cited by 32
“Although stroke incidence was reduced in the treatment group, there was an increase in hospitalizations for unstable angina [224].”
Influential
Folate and breast cancer: what about high-risk women?
Kotsopoulos, J., Kim, Y., & Narod, S. A. (2012) · Cancer Causes & Control · doi:10.1007/s10552-012-0022-y · Cited by 27
Prevention and management of co-morbidities in SLE
Bichile, T., & Petri, M. (2014) · La Presse Médicale · doi:10.1016/j.lpm.2014.03.009 · Cited by 28
L-Cystathionine Protects against Homocysteine-Induced Mitochondria-Dependent Apoptosis of Vascular Endothelial Cells
Wang, X., Wang, Y., Zhang, L., Zhang, D., Bai, L., Kong, W., Huang, Y., Tang, C., Du, J., & Jin, H. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/1253289 · Cited by 27
Homocysteine, brain natriuretic peptide and chronic heart failure: a critical review
Herrmann, W., Herrmann, M., Joseph, J., & Tyagi, S. C. (2007) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2007.360 · Cited by 27
Current strategies for ischemic stroke prevention: role of multimodal combination therapies
Alberts, M. J., & Ovbiagele, B. I. (2007) · Journal of Neurology · doi:10.1007/s00415-007-0569-9 · Cited by 26
Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model
Neuman, J. C., Albright, K. A., & Schalinske, K. L. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.04.008 · Cited by 28
“effective as anticipated [38-41].”
Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
Wang, L., Li, H., Zhou, Y., Jin, L., & Liu, J. (2014) · European Journal of Nutrition · doi:10.1007/s00394-014-0729-5 · Cited by 27
“5 mg), vitamin B6 (25–50 mg), and B12 (1 mg) in patients with cardiovascular or chronic kidney diseases has serious side effects, including impaired renal functions and increased risks of vascular events [9, 20].”
Background
C1 metabolism and CVD outcomes in older adults
McNulty, H., Strain, J., Pentieva, K. D., & Ward, M. (2011) · Proceedings of The Nutrition Society · doi:10.1017/s0029665111003387 · Cited by 28
Optimal management of peripheral arterial disease for the non-specialist.
O'Donnell, M. E., Reid, J., Lau, L. L., Hannon, R. J., & Lee, B. (2011) · Europe PMC (PubMed Central) · Cited by 27
Homocysteine levels and MTHFR polymorphisms in young patients with acute myocardial infarction: a case control study.
Eftychiou, C., Antoniades, L., Makri, L., Koumas, L., Costeas, P., Kyriakou, E., Nicolaides, E. P., & Papadogiannis, D. E. (2012) · PubMed · Cited by 27
Cardiovascular Disease
Walden, R., & Tomlinson, B. (2011) · Oxidative stress and disease · doi:10.1201/b10787-17 · Cited by 27
The Effect of Mesna on Plasma Total Homocysteine Concentration in Hemodialysis Patients
Urquhart, B. L., Freeman, D. J., Spence, J. D., & House, A. A. (2007) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2006.10.002 · Cited by 27

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

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Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

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