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Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

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  • Sabrina Schlesinger
  • Svenja R Sonntag
  • Wolfgang Lieb
  • Renke Maas

Abstract

Background: A growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies. Methods: Relevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis. Results: For ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples. Conclusions: The dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches.

Suggested Citation

  • Sabrina Schlesinger & Svenja R Sonntag & Wolfgang Lieb & Renke Maas, 2016. "Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-26, November.
  • Handle: RePEc:plo:pone00:0165811
    DOI: 10.1371/journal.pone.0165811
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    References listed on IDEAS

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    1. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
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    1. Vinitha N. Ragavan & Pramod C. Nair & Natalia Jarzebska & Ramcharan Singh Angom & Luana Ruta & Elisa Bianconi & Silvia Grottelli & Natalia D. Tararova & Daniel Ryazanskiy & Steven R. Lentz & Sara Tomm, 2023. "A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Wojciech Wołyniec & Katarzyna Kasprowicz & Joanna Giebułtowicz & Natalia Korytowska & Katarzyna Zorena & Maria Bartoszewicz & Patrycja Rita-Tkachenko & Marcin Renke & Wojciech Ratkowski, 2019. "Changes in Water Soluble Uremic Toxins and Urinary Acute Kidney Injury Biomarkers After 10- and 100-km Runs," IJERPH, MDPI, vol. 16(21), pages 1-19, October.

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