Skip to main content

Advertisement

SpringerLink
Log in

Glycoprotein VI as a prognostic biomarker for cardiovascular death in patients with symptomatic coronary artery disease

  • Original Paper
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

Abstract

Background

Platelets play a critical role in arterial thrombosis, acute coronary syndrome (ACS) and stroke. Platelet collagen receptor glycoprotein VI (GPVI) is associated with acute coronary events and a poor clinical outcome.

Methods

Between January 2006 and March 2009, we evaluated 2,213 consecutive patients in a prospective study design, who presented with chest pain. Among 1,819 patients (82.2%) who underwent coronary angiography, 1,652 patients (90.8%) showed a coronary and 167 patients (9.2%) a non-coronary origin of chest pain. 901 patients (54.5%) presented with an ACS, 751 (45.5%) with a stable angina pectoris. Clinical outcome was performed by a predefined structured telephone interview after a 3-month follow-up (92.8%:1,533 of 1,652 patients).

Results

Kaplan–Meier analysis for cumulative event-free survival revealed that patients with a elevated baseline GPVI expression had a poorer clinical outcome for cardiovascular death than patients with decreased GPVI levels (log rank; P = 0.040). These results were paralleled in composite cumulative survival that included myocardial infarction, stroke, and cardiovascular death (log rank; P = 0.002). Relative risk of cardiovascular death was found at 1.41 (95% CI 1.08–1.85) for platelet GPVI, 1.64 (95% CI 1.31–2.05) for brain natriuretic peptide, 1.16 (95% CI 0.81–1.64) for troponin-I and 1.33 (95% CI 0.97–1.82) for C-reactive protein.

Conclusions

Patients with CAD presenting increased levels of platelet GPVI had a poorer outcome and may profit from a dual antiplatelet therapy. Thus, GPVI may be a useful prognostic tool for adverse cardiovascular events. Future studies should substantiate GPVI for its potential role of risk prediction and consider its prognostic value to improve risk stratification.

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

Similar content being viewed by others

References

  1. Al-Tamimi M, Mu FT, Moroi M, Gardiner EE, Berndt MC, Andrews RK (2009) Measuring soluble platelet glycoprotein VI in human plasma by ELISA. Platelets 20:143–149

    Article  CAS  PubMed  Google Scholar 

  2. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 16:e148–e304

    Google Scholar 

  3. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, CHARISMA Investigators (2006) Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 354:1706–1717

    Article  CAS  PubMed  Google Scholar 

  4. Bigalke B, Geisler T, Stellos K, Langer H, Daub K, Kremmer E, Seizer P, May AE, Lindemann S, Gawaz M (2008) Platelet collagen receptor glycoprotein VI as a possible novel indicator for the acute coronary syndrome. Am Heart J 156:193–200

    Article  CAS  PubMed  Google Scholar 

  5. Bigalke B, Lindemann S, Ehlers R, Seizer P, Daub K, Langer H, Schonberger T, Kremmer E, Siegel-Axel D, May AE, Gawaz M (2006) Expression of platelet collagen receptor VI is associated with acute coronary syndrome. Eur Heart J 27:2165–2169

    Article  CAS  PubMed  Google Scholar 

  6. Bigalke B, Stellos K, Geisler T, Kremmer E, Seizer P, May A, Lindemann S, Melms A, Luft A, Gawaz M (2009) Expression of platelet glycoprotein vi is associated with transient ischemic attack and stroke. Eur J Neurol [Epub ahead of print]

  7. Bigalke B, Stellos K, Stakos D, Joos T, Pötz O, Geisler T, Bischofs C, Kremmer E, Krämer BF, Seizer P, May AE, Lindemann S, Gawaz M (2009) Influence of platelet count on the expression of platelet collagen receptor glycoprotein VI (GPVI) in patients with acute coronary syndrome. Thromb Haemost 101:911–915

    CAS  PubMed  Google Scholar 

  8. Bigalke B, Stellos K, Weig HJ, Geisler T, Seizer P, Kremmer E, Pötz O, Joos T, May AE, Lindemann S, Gawaz M (2009) Regulation of platelet glycoprotein VI (GPVI) surface expression and of soluble GPVI in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). Basic Res Cardiol 104:352–357

    Article  CAS  PubMed  Google Scholar 

  9. Brügger-Andersen T, Aarsetøy H, Grundt H, Staines H, Nilsen DW (2008) The long-term prognostic value of multiple biomarkers following a myocardial infarction. Thromb Res 123:60–66

    Article  PubMed  Google Scholar 

  10. Chung I, Choudhury A, Patel J, Lip GY (2009) Soluble, platelet-bound, and total P-selectin as indices of platelet activation in congestive heart failure. Ann Med 41:45–51

    Article  CAS  PubMed  Google Scholar 

  11. Debrunner M, Schuiki E, Minder E, Straumann E, Naegeli B, Mury R, Bertel O, Frielingsdorf J (2008) Proinflammatory cytokines in acute myocardial infarction with and without cardiogenic shock. Clin Res Cardiol 97:298–305

    Article  CAS  PubMed  Google Scholar 

  12. Geisler T, Kapp M, Göhring-Frischholz K, Daub K, Dösch C, Bigalke B, Langer H, Herdeg C, Gawaz M (2008) Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease. Heart 94:743–747

    Article  CAS  PubMed  Google Scholar 

  13. Ikonomidis I, Stamatelopoulos K, Lekakis J, Vamvakou GD, Kremastinos DT (2008) Inflammatory and non-invasive vascular markers: the multimarker approach for risk stratification in coronary artery disease. Atherosclerosis 199:3–11

    Article  CAS  PubMed  Google Scholar 

  14. James SK, Lindahl B, Siegbahn A, Stridsberg M, Venge P, Armstrong P, Barnathan ES, Califf R, Topol EJ, Simoons ML, Wallentin L (2003) N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a global utilization of strategies to open occluded arteries (GUSTO)-IV substudy. Circulation 108:275–281

    Article  CAS  PubMed  Google Scholar 

  15. Kisucka J, Chauhan AK, Zhao BQ, Patten IS, Yesilaltay A, Krieger M, Wagner DD (2009) Elevated levels of soluble P-selectin in mice alter blood–brain barrier function, exacerbate stroke and promote atherosclerosis. Blood 113:6015–6022

    Article  CAS  PubMed  Google Scholar 

  16. Kurz K, Schild C, Isfort P, Katus HA, Giannitsis E (2009) Serial and single time-point measurements of cardiac troponin T for prediction of clinical outcomes in patients with acute ST-segment elevation myocardial infarction. Clin Res Cardiol 98:94–100

    Article  CAS  PubMed  Google Scholar 

  17. Möckel M, Müller R, Vollert JO, Müller C, Danne O, Gareis R, Störk T, Dietz R, Koenig W (2007) Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II). Clin Res Cardiol 96:604–612

    Article  PubMed  Google Scholar 

  18. Morrow DA, Sabatine MS, Brennan ML, de Lemos JA, Murphy SA, Ruff CT, Rifai N, Cannon CP, Hazen SL (2008) Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18. Eur Heart J 29:1096–1102

    Article  CAS  PubMed  Google Scholar 

  19. Ndrepepa G, Braun S, Mehilli J, Niemöller K, Schömig A, Kastrati A (2007) A prospective cohort study of prognostic power of N-terminal probrain natriuretic peptide in patients with non-ST segment elevation acute coronary syndromes. Clin Res Cardiol 96:30–37

    Article  CAS  PubMed  Google Scholar 

  20. Patrono C, García Rodríguez LA, Landolfi R, Baigent C (2005) Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 353:2373–2383

    Article  CAS  PubMed  Google Scholar 

  21. Sabatine MS, Morrow DA, de Lemos JA, Gibson CM, Murphy SA, Rifai N, McCabe C, Antman EM, Cannon CP, Braunwald E (2002) Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 105:1760–1763

    Article  CAS  PubMed  Google Scholar 

  22. Sanchis J, Bosch X, Bodí V, Bellera N, Núñez J, Benito B, Ordóñez J, Consuegra L, Heras M, Llècer A (2008) Combination of clinical risk profile, early exercise testing and circulating biomarkers for evaluation of patients with acute chest pain without ST-segment deviation or troponin elevation. Heart 94:311–315

    Article  CAS  PubMed  Google Scholar 

  23. Thomas L, Müller M, Schumann G, Weidemann G, Klein G, Lunau S, Pick KH, Sonntag O (2005) Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 29:301–308

    CAS  Google Scholar 

  24. Tschoepe D, Schultheiss HP, Kolarov P, Schwippert B, Dannehl K, Nieuwenhuis HK, Kehrel B, Strauer B, Gries FA (1993) Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 88:37–42

    CAS  PubMed  Google Scholar 

  25. Tousoulis D, Kampoli AM, Stefanadi E, Antoniades C, Siasos G, Papavassiliou AG, Stefanadis C (2008) New biochemical markers in acute coronary syndromes. Curr Med Chem 15:1288–1296

    Article  CAS  PubMed  Google Scholar 

  26. Waxman DA, Hecht S, Schappert J, Husk G (2006) A model for troponin I as a quantitative predictor of in-hospital mortality. J Am Coll Cardiol 48:1755–1762

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by Grants of Deutsche Forschungsgemeinschaft (MA2186/3–1&GK794 to M.G.), Sonderforschungsbereich/Transregio19 `Inflammatorische Kardiomyopathie-Molekulare Pathogenese und Therapie` to K.S., S.L., M.G. (DFG:Li849/3-1;SFB:SFB-TR19-B8N), and program of Applied Clinical Research (AKF) of the University of Tübingen (No. 231-0-0).

Conflict of interest statement

None.

Author information

Authors and Affiliations

  1. Medizinische Klinik III, Kardiologie Und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Otfried-Müller-Str.10, 72076, Tübingen, Germany

    Boris Bigalke, Konstantinos Stellos, Tobias Geisler, Stephan Lindemann, Andreas E. May & Meinrad Gawaz

Authors
  1. Boris Bigalke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Konstantinos Stellos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tobias Geisler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stephan Lindemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas E. May
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Meinrad Gawaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris Bigalke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bigalke, B., Stellos, K., Geisler, T. et al. Glycoprotein VI as a prognostic biomarker for cardiovascular death in patients with symptomatic coronary artery disease. Clin Res Cardiol 99, 227–233 (2010). https://doi.org/10.1007/s00392-009-0109-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-009-0109-y

Keywords

Search

Navigation