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Asymmetric dimethylarginine and l-homoarginine prospectively relate to carotid wall thickness in a South African cohort

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Abstract

Background and aims

The l-arginine derivatives asymmetric (ADMA) and symmetric dimethylarginine (SDMA), as well as l-homoarginine may have opposing effects in the pathogenesis of atherosclerosis. We aimed to investigate (i) 5-year changes in arginine derivatives, and (ii) the association between baseline arginine derivatives and follow-up measures of carotid wall thickness in South Africans.

Methods and results

This study included men (n = 187) and women (n = 396) who took part in the 2010 and 2015 data collections of the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Arginine derivatives were determined in plasma with liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (cIMT) and cross-sectional wall area (CSWA) were determined with B-mode ultrasonography.

Results

Mean values of arginine derivatives did not change over time. In the study group, follow-up cIMT (β = − 0.10 p = 0.018) and CSWA (β = − 0.12; p = 0.004) inversely associated with baseline l-homoarginine, and cIMT inversely associated with ADMA (β = − 0.09; p = 0.033). In women, CSWA inversely associated with both ADMA (β = − 0.11; p = 0.034) and l-homoarginine (β = − 0.11; p = 0.024). No such associations were found in men.

Conclusion

These results suggest that higher levels of l-homoarginine may play a protective role against vascular injury and delay progression of carotid wall thickening in this cohort. The role of ADMA in atherosclerosis deserves further investigation in this population.

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Acknowledgements

The authors would like to thank all supporting staff and the participants of the PURE study and in particular in the South African leg of the PURE study: Prof A. Kruger (posthumous), Prof. M. Greeff, Prof. I. M. Kruger, Ms. P.G. Molaudzi, Ms. V. Kruger, Ms. J. Brits, Ms. P. Jardim working in the Africa Unit for Transdisciplinary Health Research (AUTHeR), Faculty of Health Sciences, North-West University, Potchefstroom, South Africa, as well as all the field workers over the years. In the international PURE study, the authors would like to acknowledge the contributions of Dr. S. Yusuf and the PURE project office staff at the Population Health Research Institute (PHRI), Hamilton Health Sciences and McMaster University, ON, Canada.

Funding

This work was financially supported by SANPAD (South Africa—the Netherlands Research Program on Alternatives in Development), PHRI (Population Health Research Institute), the MRC (Medical Research Council) of South Africa, the South African NRF (National Research Foundation) (GUN Numbers 2069139 and FA2006040700010), the North-West University, Roche Diagnostics and the German Academic Exchange Service (DAAD)-NRF. Opinions expressed and conclusions arrived at are those of the author and are not necessarily to be attributed to the DAAD-NRF.

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Authors and Affiliations

  1. Hypertension in Africa Research Team (HART), Faculty of Health Sciences, North-West University, Private Bag X1290, Potchefstroom, 2520, South Africa

    Maserame C. Mokhaneli, Carla M. T. Fourie, Shani Botha-Le Roux & Catharina M. C. Mels

  2. MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa

    Carla M. T. Fourie, Shani Botha-Le Roux & Catharina M. C. Mels

  3. Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Rainer H. Böger & Edzard Schwedhelm

  4. Deutsches Zentrum Fuer Herz-Kreislauf-Forschung E.V. (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany

    Rainer H. Böger & Edzard Schwedhelm

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  1. Maserame C. Mokhaneli
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  2. Carla M. T. Fourie
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Contributions

MCM, CMTF, SB-L, and CMCM contributed to the concept and design. MCM, CMTF, SB-L, ES and CMCM contributed to the acquisition, statistical analysis and interpretation of data, MCM wrote the manuscript. CMTF, SB-L, RHB, ES and CMCM critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work, ensuring integrity and accuracy.

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Correspondence to Catharina M. C. Mels.

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Mokhaneli, M.C., Fourie, C.M.T., Botha-Le Roux, S. et al. Asymmetric dimethylarginine and l-homoarginine prospectively relate to carotid wall thickness in a South African cohort. Amino Acids 52, 965–973 (2020). https://doi.org/10.1007/s00726-020-02866-9

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