Evidence map›Paper›PMID 12446535›Full record

SynthesisBMJ (Clinical research ed.)2002

Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.

David S Wald, Malcolm Law, Joan K Morris

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ (Clinical research ed.), 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 518 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
518citing papers in PubMed, 11 pooled it
66.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

518 citing papers in PubMed, 11 syntheses or guidelines pooled it, 1,936 citations in OpenAlex.

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  11. Homocysteine-lowering interventions for preventing cardiovascular events.The Cochrane database of systematic reviews · 2017
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  13. Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2024
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458 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

David S WaldDepartment of Cardiology, Southampton General Hospital, Southampton SO16 6YD. davidwald@hotmail.com
Malcolm Law
Joan K Morris
Southampton General Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo assess whether the association of serum homocysteine concentration with ischaemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, to quantify the effect of homocysteine reduction in preventing them.

designMeta-analyses of the above three diseases using (a) 72 studies in which the prevalence of a mutation in the MTHFR gene (which increases homocysteine) was determined in cases (n=16 849) and controls, and (b) 20 prospective studies (3820 participants) of serum homocysteine and disease risk.

main outcome measuresOdds ratios of the three diseases for a 5 micromol/l increase in serum homocysteine concentration.

resultsThere were significant associations between homocysteine and the three diseases. The odds ratios for a 5 micromol/l increase in serum homocysteine were, for ischaemic heart disease, 1.42 (95% confidence interval 1.11 to 1.84) in the genetic studies and 1.32 (1.19 to 1.45) in the prospective studies; for deep vein thrombosis with or without pulmonary embolism, 1.60 (1.15 to 2.22) in the genetic studies (there were no prospective studies); and, for stroke, 1.65 (0.66 to 4.13) in the genetic studies and 1.59 (1.29 to 1.96) in the prospective studies.

conclusionsThe genetic studies and the prospective studies do not share the same potential sources of error, but both yield similar highly significant results-strong evidence that the association between homocysteine and cardiovascular disease is causal. On this basis, lowering homocysteine concentrations by 3 micromol/l from current levels (achievable by increasing folic acid intake) would reduce the risk of ischaemic heart disease by 16% (11% to 20%), deep vein thrombosis by 25% (8% to 38%), and stroke by 24% (15% to 33%).

Indexed as

Cohort StudiesGenetic Predisposition to DiseaseHomocysteineHomozygoteHumansMethylenetetrahydrofolate Reductase (NADPH2)MutationMyocardial IschemiaOdds RatioOxidoreductases Acting on CH-NH Group DonorsProspective StudiesPulmonary EmbolismRisk FactorsVenous ThrombosisHomocysteineMethylenetetrahydrofolate Reductase (NADPH2)Oxidoreductases Acting on CH-NH Group Donors

Identifiers

PMID12446535
PMCPMC135491
OpenAlexW1995931698

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.