SynthesisPloS one2011
Reconciling the evidence on serum homocysteine and ischaemic heart disease: a meta-analysis.
Synthesis in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 6 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Morphofunctional Assessment beyond Malnutrition: Fat Mass Assessment in Adult Patients with Phenylketonuria-Systematic Review.Nutrients · 2024Pooled it
- A Meta-Prediction ofInternational journal of environmental research and public health · 2018Pooled it
- Evaluation of an association between plasma total homocysteine and schizophrenia by a Mendelian randomization analysis.BMC medical genetics · 2015Pooled it
- Association between polymorphism of MTHFR c.677C>T and risk of cardiovascular disease in Turkish population: a meta-analysis for 2.780 cases and 3.022 controls.Molecular biology reports · 2014Pooled it
- Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.The American journal of clinical nutrition · 2013Pooled it
- Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias.PLoS medicine · 2012Pooled it
- Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial.The Lancet. Neurology · 2012Trial
- Trial
- Review
- Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease.International journal of molecular sciences · 2025Review
- The polypill in the primary prevention of heart attacks and strokes: Overcoming barriers to implementation.Journal of medical screening · 2024Article
- Association Between Plasma Homocysteine Level and Mortality: A Mendelian Randomization Study.Korean circulation journal · 2023Article
- Review
- The Clinical Efficacy of Clopidogrel Bisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis.Computational and mathematical methods in medicine · 2021Article
- The determinants of maternal homocysteine in pregnancy: findings from the Ottawa and Kingston Birth Cohort.Public health nutrition · 2020Article
- Changes in one-carbon metabolism and DNA methylation in the hearts of mice exposed to space environment-relevant doses of oxygen ions (Life sciences in space research · 2019Article
- The Revised D-A-CH-Reference Values for the Intake of Vitamin BMolecular nutrition & food research · 2019Article
- The role of maternal homocysteine concentration in placenta-mediated complications: findings from the Ottawa and Kingston birth cohort.BMC pregnancy and childbirth · 2019Article
- The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art.International journal of molecular sciences · 2019Review
- One-carbon metabolism and ionizing radiation: a multifaceted interaction.Biomolecular concepts · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundResults from genetic epidemiological studies suggest that raised serum homocysteine is a cause of ischaemic heart disease, but the results of randomised trials suggest otherwise. We aimed to update meta-analyses on each type of study using the latest published data and test a hypothesis based on antiplatelet therapy use in the trials to explain the discrepancy. METHODS AND
findingsMeta-analyses of ischaemic heart disease using (i) 75 studies in which the prevalence of a mutation (CT) in the MTHFR gene (which increases homocysteine) was determined in cases (22,068) and controls (23,618), and (ii) 14 randomised trials (39,597 participants) of homocysteine lowering and ischaemic heart disease events. The summary estimates from the two analyses were compared. Meta-analysis of the MTHFR studies showed a statistically significantly increased risk of ischaemic heart disease in TT compared with CC homozygotes; odds ratio 1.16 (1.04 to 1.29) for a 1.9 µmol/L homocysteine difference (TT minus CC). Meta-analysis of randomised trials showed no significant reduction in IHD risk from folic acid; relative risk 1.00 (0.93 to 1.08), despite a reduction in homocysteine of 3.3 µmol/L. There was a statistically significant difference in risk reduction between the 5 trials with the lowest prevalence of antiplatelet therapy (60% on average, usually aspirin), RR 0.93 (0.84 to 1.05) and the 5 trials with the highest prevalence (91% on average), RR 1.09 (1.00 to 1.19), p = 0.037 for the difference.
conclusionDiscordant results from MTHFR studies and randomised trials could be explained by aspirin reducing or negating the anti-platelet effect of lowering homocysteine. On this basis, folic acid would have a role in the primary prevention of ischaemic heart disease, when aspirin is not taken routinely, but not in secondary prevention, when it is routine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.