Evidence map›Paper›PMID 26021436›Full record

SynthesisJournal of the American Heart Association2015

Asymmetric dimethylarginine and cardiovascular risk: systematic review and meta-analysis of 22 prospective studies.

Peter Willeit, Daniel F Freitag, Jari A Laukkanen, Susmita Chowdhury, Reeta Gobin, Manuel Mayr, Emanuele Di Angelantonio, Rajiv Chowdhury

Abstract readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 7 pooled it
–field-weighted citation impact
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

94 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Dried Blood Spots to Assess Cardiovascular-Kidney-Metabolic Health.Journal of the American Heart Association · 2025
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  11. Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017
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34 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

8 authors.

Peter WilleitCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., D.F.F., R.G., E.D.A., R.C.) King's British Heart Foundation Centre, King's College London, United Kingdom (P.W., M.M.) Department of Neurology, Medical University Innsbruck, Austria (P.W.).
Daniel F FreitagCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., D.F.F., R.G., E.D.A., R.C.).
Jari A LaukkanenInstitute of Public Health, School and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland (J.A.L.).
Susmita ChowdhuryPublic Health Genomics Foundation, Cambridge, United Kingdom (S.C.).
Reeta GobinCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., D.F.F., R.G., E.D.A., R.C.) School of Medicine, University of Guyana, Guyana (R.G.).
Manuel MayrKing's British Heart Foundation Centre, King's College London, United Kingdom (P.W., M.M.).
Emanuele Di AngelantonioCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., D.F.F., R.G., E.D.A., R.C.).
Rajiv ChowdhuryCardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (P.W., D.F.F., R.G., E.D.A., R.C.).

Funding

Austrian Science Fund FWF J 3679British Heart Foundation FS/13/2/29892British Heart Foundation RG/08/014/24067Medical Research Council MR/L003120/1
6 · The paper itself

Abstract

backgroundAsymmetric dimethylarginine (ADMA) inhibits the production of nitric oxide, a key regulator of the vascular tone, and may be important in the development of cardiovascular disease (CVD). Our aim was to reliably quantify the association of ADMA and its isomer symmetric dimethylarginine (SDMA) with the risk of CVD outcomes in long-term cohort studies. METHODS AND

resultsData were collated from 22 prospective studies involving a total of 19 842 participants, which have recorded 2339 CVD, 997 coronary heart disease, and 467 stroke outcomes during a mean follow-up of 7.1 years. In a comparison of individuals in the top with those in the bottom third of baseline ADMA values, the combined risk ratios were 1.42 (95% confidence interval: 1.29 to 1.56) for CVD, 1.39 for coronary heart disease (1.19 to 1.62), and 1.60 for stroke (1.33 to 1.91). Broadly similar results were observed according to participants' baseline disease status (risk ratios for CVD: 1.35 [1.18 to 1.54] in general populations; 1.47 [1.16 to 1.87] in individuals with pre-existing CVD; and 1.52 [1.26 to 1.84] in individuals with pre-existing kidney disease) and by different study characteristics, including geographical location, sample type, assay method, number of incident outcomes, and level of statistical adjustment (all P values>0.05). In contrast, in 8 prospective studies involving 9070 participants and 848 outcomes, the corresponding estimate for SDMA concentration was 1.32 (0.92 to 1.90) for CVD.

conclusionsAvailable prospective studies suggest associations between circulating ADMA concentration and CVD outcomes under a broad range of circumstances. Further research is needed to better clarify these associations, particularly in large general population studies.

Indexed as

ArginineCardiovascular DiseasesHumansOdds RatioProspective StudiesStrokeArginineN,N-dimethylarginineasymmetric dimethylargininecardiovascular diseasesmeta‐analysisprospective studies

Identifiers

PMID26021436
PMCPMC4599532

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Registered trials

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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.