Do Homoarginine and Asymmetric Dimethylarginine Act Antagonistically in the Cardiovascular System?

– Reply –

With great interest we read the Letter to the Editor from Tsikas and Kayacelebi. The authors’ comment on the results of our study related to an effect of tobacco smoking on the emerging cardiovascular risk factor L-homoarginine.¹ As pointed out by Tsiakas and Kayacebi, we observed a statistically significant decrease in the L-homoarginine plasma concentration in tobacco smokers when compared with nonsmokers, and a significant increase in the asymmetric dimethylarginine (ADMA) concentration. We agree with them that our results may suggest antagonistic activity of tobacco smoke components on both markers. Observed changes in both markers would have a synergistic effect, leading to endothelial dysfunction. In our study, we focused on L-homoarginine, because of higher differences in its plasma concentrations between the groups of smokers and nonsmokers. The results presented by Tsikas and Kayacelebi encouraged us to perform a secondary analysis of our data comparing the molar ratio of L-homoarginine to ADMA among smokers and nonsmokers in our population.

In fact, we were able to detect very strong association between smoking status and the L-homoarginine/ADMA ratio. The mean L-homoarginine/ADMA ratio in smokers was 5.7 (95% CI 5.5–6.0, range 2.0–11.4) and 4.2 in nonsmokers (95% CI 4.1–4.8, range 1.4–10.0; P<0.05). Prediction (β) and r² coefficients for our model increased by 37.5 and 44.3%, respectively, compared with the model including L-homoarginine as a dependent variable. After correcting for BMI, plasma creatinine and blood lead concentrations, the difference in the L-homoarginine/ADMA ratio between smokers and nonsmokers was even higher and increased by approximately one-third, reaching 22.8% (95% CI 13.6–30.4).

The results of our secondary analysis suggest that the L-homoarginine/ADMA ratio may actually be a better marker of cardiovascular risk elevated by tobacco smoke. However, there is still a need for further research to understand the mechanisms of synergistic changes in both markers and their utility in the assessment of cardiovascular risk.

Acknowledgments

We thank Craig Steger for editorial assistance. This study was supported by the Polish Ministry of Science and Higher Education grant number N N404 211837.

Disclosures

Conflict of Interest: MLG received research funding from Pfizer, manufacturer of stop smoking medications. The other authors declare they have no actual or potential competing financial interests.

• Andrzej Sobczak, PhD
• Institute of Occupational Medicine and Environmental Health, Department of Chemical Hazards and Genetic Toxicology, Department of General and Analytical Chemistry, Medical University of Silesia, Sosnowiec, Poland
• Department of General and Analytical Chemistry, Medical University of Silesia, Sosnowiec, Poland
• Adam Prokopowicz, PhD
• Magdalena Szula
• Marzena Zaciera, PhD
• Jolanta Kurek
• Institute of Occupational Medicine and Environmental Health, Department of Chemical Hazards and Genetic Toxicology, Sosnowiec, Poland
• Malgorzata Radek
• Department of Laboratory Diagnostics, City Hospital 1, Olkusz, Poland
• Maciej Lukasz Goniewicz, PhD
• Roswell Park Cancer Institute, Department of Health Behavior, Buffalo, NY, USA

(Released online June 16, 2014)

Reference

• 1.    Sobczak A, Prokopowicz A, Radek M, Szula M, Zaciera M, Kurek J, et al. Tobacco smoking decreases plasma concentration of the emerging cardiovascular risk marker, L-homoarginine. Circ J 2014; 78: 1254–1258.