L-Arginine and SDMA Serum Concentrations Are Associated with Subclinical Atherosclerosis in the Study of Health in Pomerania (SHIP)

PLoS One. 2015 Jun 22;10(6):e0131293. doi: 10.1371/journal.pone.0131293. eCollection 2015.

Abstract

Objective: Even though ˪-arginine (ARG) derivatives can predict cardiovascular mortality, their role as atherosclerotic biomarkers is unclear. We tested the hypothesis if asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and the sum of both (DMA) are positively, while ARG and ARG/ADMA ratio are inversely associated with carotid intima-media thickness (cIMT) and atherosclerotic plaque in the carotid artery.

Approach and results: Cross-sectional data of 1999 subjects (age: 45-81 years; 48.2% ♀) from the population-based Study of Health in Pomerania (SHIP-0) was used. Analysis of variance and logistic regression models were calculated and all adjusted models were corrected for sex, age, smoking status, waist-to-hip ratio and estimated glomerular filtration rate. Increased cIMT (>75th age-sex specific percentile) was found in 517 subjects (25.7%), while atherosclerotic plaque was detected in 1413 subjects (70.4%). SDMA tertiles were significantly positively associated with larger cIMT among subjects with high SDMA levels [>66th: 0.82 (95%-CI 0.80; 0.85) mm]. High SDMA levels were related to a higher odds ratio (OR) of increased cIMT [OR 1.39 (95%-CI 1.08; 1.79)]. Furthermore, ARG was positively associated with atherosclerotic plaques [OR 1.41 (95%-CI 1.07; 1.85)]. No relation was found for ADMA and atherosclerosis.

Conclusions: In conclusion, the hypothesis of a positive association between SDMA with an increased cIMT was confirmed. Unexpectedly, ARG was positively related to atherosclerotic plaque. In view of these inconsistent findings, the impact of ARG derivatives as atherosclerotic biomarkers deserves further research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Atherosclerosis / blood*
  • Carotid Intima-Media Thickness
  • Carotid Stenosis / blood
  • Cross-Sectional Studies
  • Female
  • Germany
  • Humans
  • Male
  • Middle Aged

Substances

  • symmetric dimethylarginine
  • Arginine

Grants and funding

SHIP is part of the Community Medicine Net (http://www.medizin.uni-greifswald.de/icm) of the University of Greifswald, which is funded by grants from the German Federal Ministry of Education and Research (BMBF, grant 01ZZ96030, 01ZZ0701); the Ministry for Education, Research, and Cultural Affairs; and the Ministry for Social Affairs of the Federal State of Mecklenburg–West Pomerania as well by the DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) and by the BMBF (Bundesministerium für Bildung und Forschung). Dr. Atzler acknowledges the support of the European Union under a Marie Curie Intra-European Fellowship for Career Development. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.