Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: A randomized, controlled trial

Abstract

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/mu l) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T-1), 6-hours (T-2), and on the 5th day postoperatively (T-3). 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/mu l) at all time points compared with placebo (T-1, 2.30 +/- 0.02 versus 1.58 +/- 0.03, p < 0.001; T-2, 5.00 +/- 0.06 versus 2.19 +/- 0.06, p < 0.001; T-3, 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 (T-1, 0.8 +/- 0.1 versus 2.2 +/- 1.5, p < 0.001; T-2, 72.9 +/- 3.2 versus 96.0 +/- 3.6, p < 0.001; T-3, 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.