Asymmetric dimethylarginine – a marker of repeated cardiovascular events in patients with comorbid pathology


Keywords: asymmetric dimethylarginine, acute myocardial infarction, type 2 diabetes mellitus.

Abstract

Annotation. Today, diseases of the cardiovascular system retain their leading position among the incidence in the world. The presence of comorbid pathology in the form of type 2 diabetes mellitus (DM) significantly complicates the course of these diseases, worsening its prognosis. The aim of the study: to analyze the prognostic value of asymmetric dimethylarginine (ADMA) as a marker of recurrent cardiovascular events in patients with acute myocardial infarction with type 2 diabetes for 6 months of follow-up. 120 patients were examined: group 1 – patients with acute myocardial infarction (AMI) in combination with type 2 diabetes mellitus (n=70), group 2 - patients with isolated AMI (n=50). The control group included 20 practically healthy individuals. All patients underwent general clinical and instrumental examinations, on the first day of AMI the level of ADMA was determined using a commercial test system "Human Asymmetrical Dimethylarginine ELISA". Statistical processing of the obtained data was performed using the software package StatSoft Inc, USA – "Statistica 6.0". The analysis of the average level of ADMA showed a significantly higher value of this indicator in patients with AMI in combination with type 2 DM than in patients without concomitant type 2 DM 2.57 times (1.57±0.11 μmol / l and 0.61±0.06 μmol / l, respectively), (p<0,05. ADMA level >1,72 μmol / l in patients with AMI in combination with type 2 DM and >0,69 μmol / l in patients with AMI without concomitant type 2 DM was identified as a predictor of recurrent acute myocardial infarction within 6 months of follow-up. Thus, the level of ADMA was higher in the presence of comorbid pathology in the form of type 2 DM in patients with AMI, reflecting endothelial dysfunction combining disease. It is advisable to further study this indicator of endothelial dysfunction as a predictor of the adverse course of AMI in combination with concomitant type 2 DM.

References

[1] Benjamin, E. J., Blaha, M. J., Chiuve, S. E., Cushman, M., Das, S. R., Deo, R., … & Muntner, P. (2017). Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation, 135(10), 146-603. doi: 10.1161/CIR.0000000000000485

[2] Bora, S., & Shankarrao, P. (2021). Carbonyl stress in diabetics with acute coronary syndrome. Clin Chim Acta, 520, 78-86. doi: 10.1016/j.cca.2021.06.002

[3] Csiszar, B., Marton, Z., Riba, J., Csecsei, P., Nagy, L., Toth, K., … & Molnar, T. (2021). L-arginine, asymmetric and symmetric dimethylarginine for early outcome prediction in unselected cardiac arrest victims: a prospective cohort study. Intern Emerg Med., Jun 3. doi: 10.1007/s11739-021-02767-z

[4] Dedov, I. I., Shestakova, M. V., & Galstyan, G. R. (2015). Алгоритмы специализированной медицинской помощи больным сахарным диабетом [Algorithms for specialized medical care for patients with diabetes mellitus]. Сахарный диабет – Diabetes mellitus, 18(1S), 1-112.

[5] Delano, M. J., & Ward, P. A. (2016). The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev., 274(1), 330-353. doi: 10.1111/imr.12499

[6] Fleischmann, C., Thomas-Rueddel, D. O., Hartmann, M., Hartog, C. S., Welte, T., Heublein, S., … & Reinhart, K. (2016). Hospital incidence and mortality rates of sepsis. Dtsch Arztebl Int., 113(10), 159-166. doi: 10.3238/arztebl.2016.0159

[7] Goff, D. C., Lioyd-Jones, D. M., Bennett, G., Coady, S., D'Agostino Sr, R. B., Gibbons, R. … & Wilson, P. W. F. (2014). 2013 ACCAHA Guideline on the Assessment of Cardiovascular Risk. J Am Coll Cardiol., 63(25), 2935-2959. doi: 10.1016/j.jacc.2013.11.005

[8] Hannemann, J., Appel, D., Seeberger-Steinmeister, M., Brüning, T., Zummack, J., & Böger, R. (2020). Sequence Variation in the DDAH1 Gene Predisposes for Delayed Cerebral Ischemia in Subarachnoidal Hemorrhage. J Clin Med., 9(12), 3900. doi: 10.3390/jcm9123900

[9] Kantae, V., Krekels, E. H. J., Van Esdonk, M. J., Lindenburg, P., Harms, A. C., Knibbe, C. A. J., … & Hankemeier, T. (2017). Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: Towards personalized drug therapy: An addition to the topical collection “Recent Advances in Pharmacometabolomics: Enabling Tools for Precision Medicine”. Metabolomics, 13. doi: 10.1007/s11306-017-1189-8

[10] Keller, A., Becker, C., Nienhaus, K., Beck, K., Vincent, A., Sutter, R., … & Hunziker, S. (2020). Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest-Results from the Prospective, Observational COMMUNICATE Trial. J Clin Med., 9(12), 3815. doi: 10.3390/jcm9123815

[11] Kornienko, E. A., Oynotkinova, O. Sh., Baranov, A. P., Goncharova, E. I., & Ivanov, D. V. (2015) Современные взгляды на єтиопатогенез инфаркта миокарда при сахарном диабете 2 типа и методы лечения [Modern views on the thyopathogenesis of myocardial infarction in type 2 diabetes mellitus and methods of treatment]. Вестник новых медицинских технологий – Bulletin of new medical technologies, 2, 3-8.dоі: 10.12737/11912

[12] Li, Q., Chen, Y., Li, B., Luo, C., Zuo, S., Liu, X., … & Feng, H. (2016). Hemoglobin induced NO/cGMP suppression Deteriorate Microcirculation via Pericyte Phenotype Transformation after Subarachnoid Hemorrhage in Rats. Sci. Rep., 6, 22070. doi: 10.1038/srep22070

[13] Menshikova, I. G., Loskutova, N. V., Sklyar, I. V., Lеvanova, T. V., & Mironova, O. A. (2015). Клиника, диагностика, принципы лечения с основами физической реабилитации больных острым инфарктом миокарда [Clinic, diagnostics, principles of treatment with the basics of physical rehabilitation of patients with acute myocardial infarction]. Благовещенск: Амурская ГМА – Blagoveshchensk: Amur State Medical Academy.

[14] Németh, B., Kustán, P., Németh, A., Lenkey, Z., Cziráki, A., Kiss, I., … & Ajtay, Z. (2016). Asymmetric dimethylarginine: predictor of cardiovascular diseases? Orv Hetil. Article in Hu, 157(13), 483-7. doi: 10.1556/650.2016.30396

[15] Nickler, M., Ottiger, M., Steuer, C., Huber, A., Anderson, J. B., Muller, B., & Schuetz, P. (2015). Systematic review regarding metabolic profiling for improved pathophysiological understanding of disease and outcome prediction in respiratory infections. Respir. Res., 16, 125. doi: 10.1186/s12931-015-0283-6

[16] Panchal, A. R., Bartos, J. A., Cabañas, J. G., Donnino, M. W., Drennan, I. R., Hirsch, K. G., … & Berg, K. M. (2020). Part 3: adult basic and advanced life support: 2020 American heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, 142(16, 2), 366-468. doi: 10.1161/CIR.0000000000000916

[17] Sandroni, C., Grippo, A., & Nolan, J. P. (2020). ERC-ESICM guidelines for prognostication after cardiac arrest: time for an update. Intensive Care Med., 46(10), 1901-1903. doi: 10.1007/s00134-020-06224-x

[18] Schlesinger, S., Sonntag, S. R., Lieb, W., & Maas, R. (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, 11(11). doi: 10.1371/journal.pone.0165811

[19] Schluep, M., Gravesteijn, B. Y., Stolker, R. J., Endeman, H., & Hoeks, S. E. (2018). One-year survival after in-hospital cardiac arrest: a systematic review and meta-analysis. Resuscitation, 132, 90-100. doi: 10.1016/j.resuscitation.2018.09.001

[20] Schmitt, V., Leuschner, A., Jünger, C., Pinto, A., Hahad, O., Schulz, A., … & Münzel, T. (2021). Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study. Clin Res Cardiol., 2021. doi: 10.1007/s00392-021-01879-y

[21] Strobel, J., Müller, F., Zolk, O., Endress, B., König, J., Fromm, M. F., … & Maas, R. (2013). Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1). Amino Acids, 45(4), 989-1002. doi: 10.1007/s00726-013-1556-3

[22] Vallance, P., Leone, A., Calver, A., Collier, J., & Moncada, S. (1992). Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet, 339(8793), 572-5. doi: 10.1016/0140-6736(92)90865-z

[23] Winkler, M., Nierhaus, A., Rösler, G., Lezius, S., Harlandt, O., Schwedhelm, E., … & Kluge, S. (2018). Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival. Critical Care, 22(1), 216. doi: 10.1186/s13054-018-2090-1

[24] Yan, S., Gan, Y., & Jiang, N. (2020). The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis. Crit Care, 24(1), 61. doi: 10.1186/s13054-020-2773-2

[25] Zhang, H., Chen, J., Chen, С., Wan, Н., Chen, Y., Wang, Y., … & Lu, Y. (2021). Exposure to phthalates and cardiovascular diseases in Chinese with type 2 diabetes. Environ Sci Pollut Res Int., 28(41):58113-58122. doi: 10.1007/s11356-021-14807-4
Published
2021-11-30
How to Cite
Feldman, D. A. (2021). Asymmetric dimethylarginine – a marker of repeated cardiovascular events in patients with comorbid pathology. Reports of Vinnytsia National Medical University, 25(4), 567-571. https://doi.org/https://doi.org/10.31393/reports-vnmedical-2021-25(4)-09