Skip to main content

Advertisement

SpringerLink
Log in

High clinical accuracy of asymmetric dimethylarginine and symmetric dimethylarginine in patients with ischemic heart disease

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Elevated plasma concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were found in various clinical settings including coronary heart disease. To assess ADMA and SDMA diagnostic validity in patients with different stages of ischemic heart disease, we studied these markers in patients having stable angina pectoris (SAP), unstable angina (USAP), and acute myocardial infarction (AMI). The results were compared with the values of healthy individuals. Plasma ADMA and SDMA levels were measured by high-performance liquid chromatography. In all patient groups both markers were significantly elevated in comparison with control ones (p < 0.001). In SAP patients, the median ADMA value was 0.75 (0.31–2.73) μmol/L, and SDMA 1.11 (0.69–0.1.42) μmol/L, in USAP patients, the marker values were 0.94 (0.34–3.13) μmol/L and 1.23 (0.88–4.72) μmol/L, and in AMI patients, 0.98 (0.48–2.01) μmol/L and 1.26 (0.75–2.93) μmol/L, while in healthy subjects they were 0.31 (0.17–0.87) μmol/L and 0.29 (0.20–0.83) μmol/L, respectively. SDMA was found significantly different in SAP and AMI patients (p < 0.05). Diagnostic accuracy was determined by receiver operating characteristic (ROC) curve analysis. The highest area under the ROC (AUC) for ADMA was obtained in AMI patients (0.976), while for SDMA in USAP patients (1.000). There was no significant difference between the AUCs. The greatest sensitivity and specificity were found in the USAP group (95.65 and 96.30 % for ADMA, and 100 % for each characteristic of SDMA). Considering these results, SDMA showed better clinical accuracy in assessing ischemic disease, where it could be used as a valid marker and a therapeutic target.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bae SW, Stuhlinger MC, Yoo HS, Yu KH, Park HK, Choi BY et al (2005) Plasma asymmetric dimethylarginine concentrations in newly diagnosed patients with acute myocardial infarction or unstable angina pectoris during two weeks of medical treatment. Am J Cardiol 95:729–733

    Article  PubMed  CAS  Google Scholar 

  • Blokhin IO, Stevens JW, Murry DJ, Galagudza MM, Shlyakhto EV, Leiper JM, Lentz SR (2009) Deficiency of dimethylarginine dimethylaminotransferase-1 exacerbates myocardial ischemia-reperfusion injury in mice. Circulation 120:S784

    Google Scholar 

  • Busch M, Fleck C, Wolf G, Stein G (2006) Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease-possible candidates for paradoxical epidemiology? Amino Acids 30(3):225–232

    Article  PubMed  CAS  Google Scholar 

  • Chen JW, Hsu NW, Wu TC, Lin SJ, Chang MS (2002) Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. Am J Cardiol 90(9):974–982

    Article  PubMed  CAS  Google Scholar 

  • Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037

    Article  PubMed  CAS  Google Scholar 

  • Cooke JP (2004) Asymmetrical dimethylarginine: the Uber marker? Circulation 109:1813–1818

    Article  PubMed  Google Scholar 

  • Delles C, Schneider MP, John S, Gekle M, Schmieder RE (2002) Angiotensin converting enzyme inhibition and angiotensin II AT1-receptor blockade reduce the levels of asymmetrical N(G), N(G)-dimethylarginine in human essential hypertension. Am J Hypertens 15(7 Pt 1):590–593

    Article  PubMed  CAS  Google Scholar 

  • Djordjević BV, Stojanović I, Ćosić V, Zvezdanović L, Deljanin-Ilić M, Dimić S, Kundalić B, Cvetković T, Jevtović-Stoimenov T (2008) Serum neopterin, nitric oxide, inducible nitric oxide synthase and tumor necrosis factor-α levels in patients with ischemic heart disease. Clin Chem Lab Med 46(8):1149–1155

    Article  PubMed  Google Scholar 

  • Fleck C, Janz A, Schweitzer F, Karge E, Schwertfeger M, Stein G (2001) Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in renal failure patients. Kidney Int 78:S14–S18

    Article  CAS  Google Scholar 

  • Fleck C, Schweitzer F, Karge E, Busch M, Stein G (2003) Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in patients with chronic kidney diseases. Clin Chim Acta 336(1–2):1–12

    Article  PubMed  CAS  Google Scholar 

  • Fliser D, Kronenberg F, Kielstein JT et al (2005) Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study. J Am Soc Nephrol 16:2456–2461

    Article  PubMed  CAS  Google Scholar 

  • Hamm CW, Braunwald E (2000) A classification of unstable angina revisited. Circulation 102:118–122

    Article  PubMed  CAS  Google Scholar 

  • Hov GG, Sagen E, Bigonah A, Asberg A (2007) Health-associated reference values for arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) measured with high-performance liquid chromatography. Scand J Clin Lab Invest 67(8):868–876

    Article  PubMed  CAS  Google Scholar 

  • Kielstein JT, Zoccali C (2005) Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age? Am J Kidney Dis 46:186–202

    Article  PubMed  CAS  Google Scholar 

  • Kielstein JT, Salpeter SR, Bode-Böger SM, Cooke JP, Fliser D (2006) Symmetric dimethylarginine (SDMA) as endogenous marker of renal function—a meta-analysis. Nephrol Dial Transpl 21:2446–2451

    Article  CAS  Google Scholar 

  • Leong T, Zylberstein D, Graham I, Lissner L, Ward D, Fogarty J, Bengtsson C, Bjorkelund C, Thelle D (2008) Asymmetric dimethylarginine independently predicts fatal and nonfatal myocardial infarction and stroke in women. 24-year follow up of the population study of women in Gothenburg. Arterioscler Thromb Vasc Biol 28:961–967

    Article  PubMed  CAS  Google Scholar 

  • Meinitzer A, Puchinger M, Winklhofer-Roob BM, Rock E, Ribalta J, Roob JM, Sundl I, Halwachs-Baumann G, Marz W (2007) Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method. Clin Chim Acta 384:141–148

    Article  PubMed  CAS  Google Scholar 

  • Meinitzer A, Keilstein JT, Pilz S, Drechsler C, Ritz E, Boehm BO, Winkelmann BR, Marz W (2011) Symmetrical and asymmetrical dimethylarginine as predictors for mortality in patients referred for coronary angiography: the ludwigshafen risk and cardiovascular health study. Clin Chem 57(1):112–121

    Article  PubMed  CAS  Google Scholar 

  • Nijveldt RJ, Teerlink T, Siroen MP, van Lambalgen AA, Rauwerda JA, van Leeuwen PA (2003) The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA). Clin Nutr 22(1):17–22

    Article  PubMed  CAS  Google Scholar 

  • Päivä H, Laakso J, Lehtimäki T, Isomustajärvi M, Ruokonen I, Laaksonen R (2003) Effect of high-dose statin treatment on plasma concentrations of endogenous nitric oxide synthase inhibitors. J Cardiovasc Pharmacol 41(2):219–222

    Article  PubMed  Google Scholar 

  • Paroni R, Fermo I, Fiorina P, Cighetti G (2005) Determination of asymmetric and symmetric dimethylarginines in plasma of hyperhomocysteinemic subjects. Amino Acids 28(4):389–394

    Article  PubMed  CAS  Google Scholar 

  • Ravani P, Tripepi G, Malberti F, Testa S, Mallamaci F, Zoccali C (2005) Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J Am Soc Nephrol 16:2449–2455

    Article  PubMed  CAS  Google Scholar 

  • Rust HL, Zurita-Lopez CI, Clarke S, Thompson PR (2011) Mechanistic studies on transcriptional coactivator protein arginine methyltransferase 1. Biochemistry 50(16):3332–3345

    Article  PubMed  CAS  Google Scholar 

  • Schulze F, Lenzen H, Hanefeld C, Bartling A, Osterziel KJ, Goudeva L, Schmidt-Lucke C, Kusus M, Maas R, Schwedhelm E, Strodter D, Simon BC, Mugge A, Daniel WG, Tillmanns H, Maisch B, Streichert T, Boger RH (2006) Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J 152(3):493.e1–e8

    Google Scholar 

  • Schulze F, Carter AM, Schwedhelm E, Ajjan R, Maas R, von Holten RA, Atzler D, Grant PJ, Boger RH (2010) Symmetric dimethylarginine predicts all-cause mortality following ischemic stroke. Atherosclerosis 208(2):518–523

    Article  PubMed  CAS  Google Scholar 

  • Schwedhelm E, Xanthakis V, Maas R, Sullivan LM, Schulze F, Riederer U, Benndorf RA, Boger RH, Vasan RS (2009) Asymmetric dimethylarginine reference intervals determined with liquid chromatography-tandem mass spectrometry: results from the Framingham offspring cohort. Clin Chem 55(8):1539–1545

    Article  PubMed  CAS  Google Scholar 

  • Sibal L, Agarwal SC, Schwedhelm E, Luneburg N, Boger RH, Home PD (2009) A study of endothelial function and circulating asymmetric dimethylarginine levels in people with Type 1 diabetes without macrovascular disease or microalbuminuria. Cardiovasc Diabetol 8:27

    Article  PubMed  Google Scholar 

  • Sibal L, Agarwal SC, Home PD, Boger RH (2010) The role of asymmetric dimethylarginine (ADMA) in endothelial dysfunction and cardiovascular disease. Curr Cardiol Rev 6(2):82–90

    Article  PubMed  CAS  Google Scholar 

  • Stuhlinger MC, Conci E, Haubner BJ, Stocker E-M, Schwaighofer J, Cooke JP, Tsao PS, Pachinger O, Metzler B (2007) Asymmetric dimethyl l-arginine (ADMA) is a critical regulator of myocardial reperfusion injury. Cardiovasc Res 75:417–425

    Article  PubMed  Google Scholar 

  • Surdacki A, Nowicki M, Sandmann J, Tsikas D, Boeger RH, Bode-Boeger SM, Kruszelnicka-Kwiatkowska O, Kokot F, Dubiel JS, Froelich JC (1999) Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol 33:652–658

    Article  PubMed  CAS  Google Scholar 

  • Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH (2004) Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 27(3):765–769

    Article  PubMed  CAS  Google Scholar 

  • Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA (2002) Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 303:131–137

    Article  PubMed  CAS  Google Scholar 

  • Valkonen VP, Laakso J, Paiva H, Lehtimaki T, Lakka TA, Isomustajarvi M et al (2003) Asymmetrical dimethylarginine (ADMA) and risk of acute coronary events. Does statin treatment influence plasma ADMA levels? Atheroscler Suppl 4:19–22

    Article  PubMed  CAS  Google Scholar 

  • Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KAA et al (2003) Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 24:28–66

    Article  PubMed  Google Scholar 

  • Wahbi N, Dalton RN, Turner C, Denton M, Abbs I, Swaminathan R (2001) Dimethylarginines in chronic renal failure. J Clin Pathol 54(6):470–473

    Article  PubMed  CAS  Google Scholar 

  • Ziegler S, Mittermayer F, Plank C, Minar E, Wolzt M, Schernthaner G-H (2005) Homocyst(e)ine-lowering therapy does not affect plasma asymmetrical dimethylarginine concentrations in patients with peripheral artery disease. J Clin Endocrinol Metabol 90(4):2175–2178

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the Ministry of Science and Technological Development of Serbia. English language was restyled by Ljiljana Markovic, senior lector, English Department, Faculty of Philosophy, University of Nis.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Institute of Biochemistry, Niš, Serbia

    B. V. Djordjević & T. Jevtović-Stoimenov

  2. Department of Chemistry, Faculty of Medicine, University of Nis, Niš, Serbia

    R. Pavlović

  3. Centre for Medical Biochemistry, Clinical Centre Nis, Niš, Serbia

    V. Ćosić & T. Ristić

  4. Institute for Cardiovascular and Rheumatic Diseases, Niška Banja, Niš, Serbia

    M. Deljanin-Ilić

  5. Clinic for Cardiovascular Diseases, Clinical Centre Nis, Niš, Serbia

    N. Krstić

Authors
  1. B. V. Djordjević
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Pavlović
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. Ćosić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Deljanin-Ilić
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Ristić
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. Krstić
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Jevtović-Stoimenov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. V. Djordjević.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Djordjević, B.V., Pavlović, R., Ćosić, V. et al. High clinical accuracy of asymmetric dimethylarginine and symmetric dimethylarginine in patients with ischemic heart disease. Amino Acids 43, 2293–2300 (2012). https://doi.org/10.1007/s00726-012-1307-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-012-1307-x

Keywords

Search

Navigation