Homocysteine lowering interventions for preventing cardiovascular events
Open accessAbstract
BACKGROUND: Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. OBJECTIVES: To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. SELECTION CRITERIA: We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. DATA COLLECTION AND ANALYSIS: We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. MAIN RESULTS: We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively. AUTHORS' CONCLUSIONS: Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events.
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A Cochrane meta-analysis of eight RCTs found homocysteine-lowering interventions did not reduce risk of fatal/non-fatal MI (RR 1.03, 95% CI 0.94-1.13), stroke (RR 0.89, 95% CI 0.73-1.08), or death by any cause (RR 1.00, 95% CI 0.92-1.09).
“The Cochrane Collaboration concluded in a recent meta-analysis of eight RCTs that homocysteine-lowering interventions did not reduce the risk of fatal/non-fatal myocardial infarction (RR 1.03, 95% CI 0.94-1.13),stroke (RR 0.89, 95% CI 0.73 -1.08), or death by any cause (RR 1.00, 95% CI 0.92-1.09).290”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [290]
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Effect of Folic Acid on Endothelial Function Following Acute Myocardial Infarction
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Flagged first, then by citations
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- Wang X Qin X Demirtas H Li J Mao G Huo Y Efficacy of folic acid supplementation in stroke prevention: a meta-analysis The Lancet 2007 369 1876 82 17544768
Cited by
Sorted by citations
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
Authors/Task Force Members:, Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Ž., Verschuren, M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs092 · Cited by 8,490 · see citing works
B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review
Kennedy, D. (2016) · Nutrients · doi:10.3390/nu8020068 · Cited by 1,055 · see citing works
Kinoshita, M., Yokote, K., Arai, H., Iida, M., Ishigaki, Y., Ishibashi, S., Umemoto, S., Egusa, G., Ohmura, H., Okamura, T., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2017 · Cited by 813 · see citing works
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Caffeine and cardiovascular health
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Triangulating Evidence through the Inclusion of Genetically Informed Designs
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The road ahead for health and lifespan interventions
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Homocysteine-lowering interventions for preventing cardiovascular events
Martí-Carvajal, A. J., Solà, I., & Lathyris, D. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006612.pub4 · Cited by 113 · see citing works
Self-citationNussbaumer-Streit, B., Klerings, I., Wagner, G., Heise, T. L., Dobrescu, A. I., Armijo-Olivo, S., Stratil, J. M., Persad, E., Lhachimi, S. K., Van Noord, M. G., et al. (2018) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2018.05.022 · Cited by 72 · see citing works
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Wargny, M., Croyal, M., Ragot, S., Gand, E., Jacobi, D., Trochu, J.-N., Prieur, X., Le May, C., Goronflot, T., Cariou, B., et al. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01505-9 · Cited by 21 · see citing works
Bjørndal, B., Ramsvik, M., Lindquist, C., Nordrehaug, J., Bruheim, I., Svardal, A., Nygård, O., & Berge, R. (2015) · Marine Drugs · doi:10.3390/md13095706 · Cited by 20 · see citing works
Basu, T., Kumar, S., Kalyan, A., Jayaswal, P., Goyal, P., Pettifer, S., & Jonnalagadda, S. R. (2016) · arXiv · doi:10.48550/arxiv.1606.06424 · Cited by 7 · see citing works
- Authors
- Martí-Carvajal, A. J., Solà, I., Lathyris, D., & Salanti, G.
- Affiliations
- G. Papanikolaou General Hospital (GR)
- University of Ioannina (GR)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- John Wiley & Sons, Ltd
- Published
- 2009-10-07
- Volume
- 8
- Issue
- 4
- Pages
- CD006612-CD006612
- ISSN
- 1361-6137 (ISSN-L)
- PMC
- PMC4164174
- OpenAlex
- W2144717748
- Cited by
- 520
- References
- 311
- Citations by year
- 2025: 16 · 2024: 18 · 2023: 32 · 2022: 30 · 2021: 48 · 2020: 47 · 2019: 41 · 2018: 31 · 2017: 33 · 2016: 45 · 2015: 42 · 2014: 34 · 2013: 31 · 2012: 26
- Type
- reference entry
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- total homocysteine, cardiovascular disease prevention, myocardial infarction, stroke, vitamin B12, folic acid, pyridoxine, cardiovascular risk factors, cardiovascular mortality, congestive heart failure, coronary artery disease, stroke prevention, myocardial infarction prevention, vitamin supplementation, randomized controlled trials, meta-analysis of trials
- MeSH terms
- Angina Pectoris, Cardiovascular Diseases, Humans, Myocardial Infarction, Vitamin B Complex, Randomized Controlled Trials as Topic, Hyperhomocysteinemia, Stroke
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 ›
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