Skip to main content
SpringerLink
Log in

Predictive value of plasma asymmetric dimethylarginine, homocysteine, and high-sensitive CRP levels in occult coronary artery disease

A multidetector-row computed tomography study

Prädiktiver Wert der Plasmawerte für asymmetrisches Dimethylarginin, Homozystein und hochsensitives CRP bei maskierter koronarer Herzkrankheit

Eine Multidetektor-Computertomographie-Studie

  • e-Herz: Original article
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

Multidetector-row computed tomography (MDCT) is an attractive noninvasive imaging modality for detecting coronary atherosclerotic plaques, which may be underestimated by conventional angiography. The aim of our study was to determine the predictive value of plasma asymmetric dimethylarginine (ADMA), homocysteine, and high-sensitivity C-reactive protein (hsCRP) levels for occult coronary artery disease (CAD).

Patients and methods

Thirty-five patients with angiographically normal coronary arteries (NCA) were consecutively included in our study. They underwent MDCT including indications and were divided into an NCA group (18 subjects, 8 male, 46 ± 8  years) and an occult CAD group (17 subjects, 11 male, 48 ± 9 years), with respect to the presence of coronary plaque. Plasma ADMA, homocysteine, and hsCRP levels were measured in blood samples.

Results

Plasma ADMA and homocysteine levels of the occult CAD group were significantly higher than those of the NCA group. A nonsignificant trend was observed for higher serum hsCRP levels in the occult CAD group. Receiver operating characteristics analysis revealed that an ADMA level of > 0.71 μmol/l could predict patients with occult CAD (sensitivity, 76 %; specificity, 67 %). The discriminative power of ADMA in distinguishing the occult CAD group from the NCA group was high (area under the curve, 0.80; CI, 0.66–0.95, p = 0.002), while it was not sufficiently high for homocysteine and hsCRP (p > 0.05).

Conclusion

Plasma ADMA is a useful parameter for predicting subclinical atherosclerosis, whereas homocysteine and hsCRP are not, and it may be complementary to the conventional cardiovascular risk factors for the selection of individuals at high risk for CAD before undertaking MDCT procedures in clinical practice.

Zusammenfassung

Hintergrund

Die Multidetektor-Computertomographie (MDCT) ist ein interessantes nichtinvasives bildgebendes Verfahren für die Erkennung koronarer atherosklerotischer Plaques, die bei der herkömmlichen Angiographie unterschätzt werden können. Ziel der vorliegenden Studie war es, den prädiktiven Wert von asymmetrischem Dimethylarginin (ADMA), Homozystein und hochsensitivem C-reaktivem Protein (hsCRP) im Plasma bei maskierter koronarer Herzkrankheit (KHK) zu untersuchen.

Methoden

In die Studie wurden nacheinander 35 Patienten mit angiographisch normalen Koronararterien (NCA) aufgenommen. Bei ihnen erfolgte bei entsprechender Indikation eine MDCT; sie wurden dann in eine NCA-Gruppe (18 Teilnehmer, 8 Männer, 46 ± 8 Jahre) und eine Gruppe mit maskierter KHK (17 Teilnehmer, 11 Männer, 48 ± 9 Jahre) unterteilt – je nach Vorliegen koronarer Plaques. In Blutproben wurden Plasma-ADMA-, -Homozystein- und -hsCRP-Werte gemessen.

Ergebnisse

Die Plasmawerte für ADMA und Homozystein waren in der Gruppe mit maskierter KHK signifikant höher als in der Gruppe mit NCA. Eine nichtsignifikante Tendenz zu höheren Serum-hsCRP-Werten wurde bei der Gruppe mit maskierter KHK festgestellt. Anhand der Receiver-operating-characteristics-Analyse zeigte sich, dass ein ADMA-Wert > 0,71 μmol/l die Erkennung von Patienten mit maskierter KHK ermöglichte (Sensitivität: 76 %; Spezifität: 67 %). Die diskriminative Power von ADMA zur Unterscheidung der Gruppe mit maskierter KHK von der NCA-Gruppe war hoch [Fläche unter der Kurve (AUC): 0,80; KI: 0,66–0,95; p = 0,002], nicht ausreichend hoch war sie jedoch für Homozystein und hsCRP (p > 0,05).

Schlussfolgerung

Der Plasma-ADMA-Wert ist ein hilfreicher Parameter zur Erkennung einer subklinischen Atherosklerose, während dies für Homozystein und hsCRP nicht gilt, und kann im klinischen Alltag ergänzend zu den herkömmlichen kardiovaskulären Risikofaktoren zur Selektion von Hochrisikopersonen für eine KHK vor einer MDCT-Untersuchung eingesetzt werden.

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

  1. Stamler J, Wentworth D, Neaton JD 9 (1986) Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 256(20):2823–2828

    Article  CAS  PubMed  Google Scholar 

  2. Pearson TA (2002) New tools for coronary risk assessment. What are their advantages and limitations? Circulation 105:886–892

    Article  PubMed  Google Scholar 

  3. Vallance P, Leone A, Calver A et al (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575

    Article  CAS  PubMed  Google Scholar 

  4. Lu TM, Ding YA, Lin SJ et al (2003) Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 24:1912–1919

    Article  CAS  PubMed  Google Scholar 

  5. Meinitzer A, Seelhorst U, Wellnitz B et al (2007) Asymmetrical dimethylarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease (the Ludwigshafen Risk and Cardiovascular Health study). Clin Chem 53:273–283

    Article  CAS  PubMed  Google Scholar 

  6. Ridker P (2001) High-sensitivity C-reactive protein. Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 103:1813–1818

    Article  CAS  PubMed  Google Scholar 

  7. The Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288:2015–2022

    Article  Google Scholar 

  8. Degertekin M, Gemici G, Kaya Z et al (2008) Safety and efficacy of patient preparation with intravenous esmolol before 64-slice computed tomography coronary angiography. Coron Artery Dis 19:33–36

    Article  PubMed  Google Scholar 

  9. HoffmannMH, Shi H, Schmitz BL et al (2005) Noninvasive coronary angiography withmultislice computed tomography. JAMA 293:2471–2478

    Article  Google Scholar 

  10. Leber AW, Knez A, Becker A et al (2004) Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 43:1241–1247

    Article  PubMed  Google Scholar 

  11. Achenbach S, Moselewski F, Ropers D et al (2004) Detection of calcified and noncalcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multidetector spiral computed tomography: a segment-based comparison with intravascular ultrasound. Circulation 109:14–17

    Article  PubMed  Google Scholar 

  12. Böger RH (2003) Association of asymmetric dimethylarginine and endothelial dysfunction. Clin Chem Lab Med 41:1467–1472

    Article  PubMed  Google Scholar 

  13. Valkonen VP, Paiva H, Salonen JT et al (2001) Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 358(9299):2127–2128

    Article  CAS  PubMed  Google Scholar 

  14. Nijveldt RJ, Teerlink T, Van Der HovenB et al (2003) Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality. Clin Nutr 22(1):23–33

    Article  CAS  PubMed  Google Scholar 

  15. Schnabel R, Blankenberg S, Lubos E et al (2005) Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 97(5):e53–e59

    Article  CAS  PubMed  Google Scholar 

  16. Evans RW, Shaten BJ, Hempel JD et al (1997) Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial. Arterioscler Thromb Vasc Biol 17:1947–1953

    Article  CAS  PubMed  Google Scholar 

  17. Starkebaum G, Harlan JM (1986) Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. J Clin Invest 77:1370–1376

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Al-Obaidi MK, Philippou H, Stubbs PJ et al (2000) Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes. Circulation 101:372–377

    Article  CAS  PubMed  Google Scholar 

  19. Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397

    Article  CAS  PubMed  Google Scholar 

  20. Koenig W, Sund M, Frohlich M et al (1999) C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study 1984–1992 Circulation 99:237–242

    Google Scholar 

  21. Fichtlscherer S, Rosenberger G, Walter DH et al (2000) Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102(9):1000–1006

    Article  CAS  PubMed  Google Scholar 

  22. Hunt ME, O’Malley PG, Vernalis MN et al (2001) C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis. Am Heart J 141(2):206–210

    Article  CAS  PubMed  Google Scholar 

  23. Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350(14):1387–1397

    Article  CAS  PubMed  Google Scholar 

  24. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E et al (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375(9709):132–140

    Article  Google Scholar 

  25. Korosoglou G, Lehrke S, Mueller D et al (2011) Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart 97(10):823–831

    Article  PubMed  Google Scholar 

  26. Laufer EM, Mingels AM, Winkens MH et al (2010) The extent of coronary atherosclerosis is associated with increasing circulating levels of high sensitive cardiac troponin T. Arterioscler Thromb Vasc Biol 30(6):1269–1275

    Article  CAS  PubMed  Google Scholar 

  27. Emond M, Mock MB, Davis KB et al (1994) Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry. Circulation 90:2645–2657

    Article  CAS  PubMed  Google Scholar 

  28. Fox K, Garcia MA, Ardissino D et al (2006) Guidelines on the management of stable angina pectoris: executive summary: the task force on the management of stable angina pectoris of the European Society of Cardiology. Eur Heart J 27:1341–1381

    Article  PubMed  Google Scholar 

  29. Farb A, Burke AP, Tang AL et al (1996) Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 93:1354–1363

    Article  CAS  PubMed  Google Scholar 

  30. Yokoya K, Takatsu H, Suzuki T et al (1999) Process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis: a study based on four serial coronary arteriograms per year. Circulation 100:903–909

    Article  CAS  PubMed  Google Scholar 

  31. Nissen SE, Tuzcu EM, Schoenhagen P et al (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352:29–38

    Article  CAS  PubMed  Google Scholar 

  32. Butler J, Shapiro M, Reiber J et al (2007) Extent and distribution of coronary artery disease: a comparative study of invasive versus noninvasive angiography with computed angiography. Am Heart J 153:378–384

    Article  PubMed  Google Scholar 

  33. Voros S, Rinehart S, Qian Z et al (2011) Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc Imaging 4(5):537–548

    Article  PubMed  Google Scholar 

  34. Boogers MJ, Broersen A, Velzen JE van et al (2012) Automated quantification of coronary plaque with computed tomography: comparison with intravascular ultrasound using a dedicated registration algorithm for fusion-based quantification. Eur Heart J 33(8):1007–1016

    Article  PubMed  Google Scholar 

  35. Versteylen MO, Kietselaer BL, Dagnelie PC et al (2013) Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome. J Am Coll Cardiol 61(22):2296–2305

    Article  PubMed  Google Scholar 

Download references

Compliance with ethical guidelines

Conflict of interest. E. Gürel, K. Tigen, T. Karaahmet, Ç. Geçmen, B. Mutlu, and Y. Başaran state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Author information

Authors and Affiliations

  1. Department of Cardiology, Ordu State Hospital, Bahçelievler Mh. 293.Sk. Gürsoy-Varol Sitesi, B-blok, No. 4/13, Ordu, Turkey

    E. Gürel

  2. Department of Cardiology, Marmara University Hospital, Istanbul, Turkey

    K. Tigen, B. Mutlu & Y. Başaran

  3. Department of Cardiology, Acibadem University Hospital, Istanbul, Turkey

    T. Karaahmet

  4. Department of Cardiology, Kartal Koşuyolu Heart and Research Hospital, Istanbul, Turkey

    Ç. Geçmen

Authors
  1. E. Gürel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Tigen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Karaahmet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ç. Geçmen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Mutlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Başaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Gürel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gürel, E., Tigen, K., Karaahmet, T. et al. Predictive value of plasma asymmetric dimethylarginine, homocysteine, and high-sensitive CRP levels in occult coronary artery disease. Herz 40, 495–501 (2015). https://doi.org/10.1007/s00059-013-4022-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-013-4022-9

Keywords

Schlüsselwörter

Search

Navigation