Effects of Preoperative Short Term Use of Atorvastatin on Endothelial Progenitor Cells after Coronary Surgery: A Randomized, Controlled Trial
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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. (ClinicalTrials.gov number, NCT01096875)
KeywordsEndothelial 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.0.05.02.00/BAP) 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.
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