Stem Cell Reviews and Reports

, Volume 8, Issue 3, pp 963–971 | Cite as

Effects of Preoperative Short Term Use of Atorvastatin on Endothelial Progenitor Cells after Coronary Surgery: A Randomized, Controlled Trial

  • Çağdaş Baran
  • Serkan Durdu
  • Klara Dalva
  • Çagın Zaim
  • Arın Dogan
  • Gokhan Ocakoglu
  • Günhan Gürman
  • Önder Arslan
  • Ahmet Rüçhan AkarEmail author



We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG).


Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/μl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T1), 6-hours (T2), and on the 5th day postoperatively (T3). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery.


There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/μl) at all time points compared with placebo (T1, 2.30 ± 0.02 versus 1.58 ± 0.03, p < 0.001; T2, 5.00 ± 0.06 versus 2.19 ± 0.06, p < 0.001; T3, 3.03 ± 0.08 versus 1.78 ± 0.02, p < 0.001). Postoperative hsCRP rise were inversely correlated with EPC count, and were significantly lower in the statin group (T1, 0.8 ± 0.1 versus 2.2 ± 1.5, p < 0.001; T2, 72.9 ± 3.2 versus 96.0 ± 3.6, p < 0.001; T3, 4.3 ± 1.2 versus 11.4 ± 4.1, p < 0.001). Furthermore, the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo (3.3% versus 23%, p = 0.02).


Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. ( number, NCT01096875)


Endothelial progenitor cells Statins CABG C-reactive protein Cardiopulmonary bypass 



This study was supported in part by a cooperative agreement funded by the Ankara University School of Medicine Research Council (B.30.2.ANK. and Ankara University Stem Cell Institute Research Fund, Turkey. We are indebted to Leyla Yigit for her initial statistical review, Gunseli Cubukcuoglu Deniz, Emre Ozsoylu, and Nazli Kozan for technical assistance, and to Pharmacy Department for preparing study medication. The authors thank all the surgical teams who contributed patients to the study.


The authors declare no potential conflicts of interest.

Statement of Responsibility

The authors had full access to the patients’ data and take full responsibility for their integrity.


  1. 1.
    Asahara, T., Murohara, T., Sullivan, A., et al. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science, 275, 964–967.PubMedCrossRefGoogle Scholar
  2. 2.
    Hristov, M., Erl, W., & Weber, P. C. (2003). Endothelial progenitor cells: Mobilization, differentiation, and homing. Arteriosclerosis, Thrombosis, and Vascular Biology, 23, 1185–1189.PubMedCrossRefGoogle Scholar
  3. 3.
    Rafii, S., & Lyden, D. (2003). Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nature Medicine, 9, 702–712.PubMedCrossRefGoogle Scholar
  4. 4.
    Shantsila, E., Watson, T., & Lip, G. Y. (2007). Endothelial progenitor cells in cardiovascular disorders. Journal of the American College of Cardiology, 49, 741–752.PubMedCrossRefGoogle Scholar
  5. 5.
    Scheubel, R. J., Zorn, H., Silber, R. E., et al. (2003). Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. Journal of the American College of Cardiology, 42, 2073–2080.PubMedCrossRefGoogle Scholar
  6. 6.
    Roberts, N., Xiao, Q., Weir, G., Xu, Q., & Jahangiri, M. (2007). Endothelial progenitor cells are mobilized after cardiac surgery. The Annals of Thoracic Surgery, 83, 598–605.PubMedCrossRefGoogle Scholar
  7. 7.
    Vasa, M., Fichtlscherer, S., Adler, K., et al. (2001). Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation, 103, 2885–2890.PubMedCrossRefGoogle Scholar
  8. 8.
    Mannacio, V. A., Iorio, D., De-Amicis, V., Di-Lello, F., & Musumeci, F. (2008). Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: A randomized trial. The Journal of Thoracic and Cardiovascular Surgery, 136, 1541–1548.PubMedCrossRefGoogle Scholar
  9. 9.
    Hristov, M., Fach, C., Becker, C., et al. (2007). Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment. Atherosclerosis, 192, 413–420.PubMedCrossRefGoogle Scholar
  10. 10.
    Spadaccio, C., Pollari, F., Casacalenda, A., et al. (2010). Atorvastatin increases the number of endothelial progenitor cells after cardiac surgery: A randomized control study. Journal of Cardiovascular Pharmacology, 55, 30–38.PubMedCrossRefGoogle Scholar
  11. 11.
    Edmunds, L. H., Jr., & Colman, R. W. (2006). Thrombin during cardiopulmonary bypass. The Annals of Thoracic Surgery, 82, 2315–2322.PubMedCrossRefGoogle Scholar
  12. 12.
    Schmid, F. X., Vudattu, N., Floerchinger, B., et al. (2006). Endothelial apoptosis and circulating endothelial cells after bypass grafting with and without cardiopulmonary bypass. European Journal of Cardio-Thoracic Surgery, 29, 496–500.PubMedCrossRefGoogle Scholar
  13. 13.
    Akar, A. R., Durdu, S., Arat, M., et al. (2009). Five-year follow-up after transepicardial implantation of autologous bone marrow mononuclear cells to ungraftable coronary territories for patients with ischaemic cardiomyopathy. European Journal of Cardio-Thoracic Surgery, 36, 633–643.PubMedCrossRefGoogle Scholar
  14. 14.
    Durdu, S., Akar, A. R., Arat, M., Sancak, T., Eren, N. T., & Ozyurda, U. (2006). Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. Journal of Vascular Surgery, 44, 732–739.PubMedCrossRefGoogle Scholar
  15. 15.
    Hristov, M., Schmitz, S., & Schuhmann, C. (2009). An optimized flow cytometry protocol for analysis of angiogenic monocytes and endothelial progenitor cells in peripheral blood. Cytometry Part A, 75, 848–853.CrossRefGoogle Scholar
  16. 16.
    Rustemeyer, P., Wittkowski, W., Jurk, K., & Koller, A. (2006). Optimized flow cytometric analysis of endothelial progenitor cells in peripheral blood. Journal of Immunoassay & Immunochemistry, 27, 77–88.CrossRefGoogle Scholar
  17. 17.
    Leone, A. M., Rutella, S., Giannico, M. B., et al. (2008). Effect of intensive vs. standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial. International Journal of Cardiology, 130, 457–462.PubMedCrossRefGoogle Scholar
  18. 18.
    Kureishi, Y., Luo, Z., Shiojima, I., et al. (2000). The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nature Medicine, 6, 1004–1010.PubMedCrossRefGoogle Scholar
  19. 19.
    Dimmeler, S., Aicher, A., Vasa, M., et al. (2001). HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. The Journal of Clinical Investigation, 108, 391–397.PubMedGoogle Scholar
  20. 20.
    Leone, A. M., Valgimigli, M., Giannico, M. B., et al. (2009). From bone marrow to the arterial wall: The ongoing tale of endothelial progenitor cells. European Heart Journal, 30, 890–899.PubMedCrossRefGoogle Scholar
  21. 21.
    Choi, Y. H., Neef, K., Reher, M., et al. (2010). The influence of pre-operative risk on the number of circulating endothelial progenitor cells during cardiopulmonary bypass. Cytotherapy, 12, 79–87.PubMedCrossRefGoogle Scholar
  22. 22.
    Werner, N., Kosiol, S., Schiegl, T., et al. (2005). Circulating endothelial progenitor cells and cardiovascular outcomes. The New England Journal of Medicine, 353, 999–1007.PubMedCrossRefGoogle Scholar
  23. 23.
    Schmidt-Lucke, C., Rossig, L., Fichtlscherer, S., et al. (2005). Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: Proof of concept for the clinical importance of endogenous vascular repair. Circulation, 111, 2981–2987.PubMedCrossRefGoogle Scholar
  24. 24.
    Hill, J. M., Zalos, G., Halcox, J. P., et al. (2003). Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. The New England Journal of Medicine, 348, 593–600.PubMedCrossRefGoogle Scholar
  25. 25.
    Pasceri, V., Patti, G., Nusca, A., Pristipino, C., Richichi, G., & Di-Sciascio, G. (2004). Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: Results from the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) study. Circulation, 110, 674–678.PubMedCrossRefGoogle Scholar
  26. 26.
    Antoniades, C., Bakogiannis, C., Tousoulis, D., et al. (2010). Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation, 122, 66–73.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Çağdaş Baran
    • 1
  • Serkan Durdu
    • 1
    • 2
  • Klara Dalva
    • 3
  • Çagın Zaim
    • 1
  • Arın Dogan
    • 1
    • 4
  • Gokhan Ocakoglu
    • 5
  • Günhan Gürman
    • 2
    • 3
  • Önder Arslan
    • 2
    • 3
  • Ahmet Rüçhan Akar
    • 1
    • 2
    Email author
  1. 1.Department of Cardiovascular Surgery, Heart CenterAnkara University School of MedicineAnkaraTurkey
  2. 2.Stem Cell InstituteAnkara UniversityAnkaraTurkey
  3. 3.Department of HematologyAnkara University School of MedicineAnkaraTurkey
  4. 4.Biotechnology InstituteAnkara UniversityAnkaraTurkey
  5. 5.Department of BiostatisticsUludag University School of MedicineBursaTurkey

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