Abstract 2369: Effects Of Rosuvastatin Withdrawal On Circulating Progenitor Cells And Endothelial Function In Patients With Chronic Heart Failure After Cessation Of Treatment
In patients (pts) with chronic heart failure (CHF) endothelial dysfunction has been partially attributed to an impaired regenerative capacity of circulating endothelial progenitor cells (CPCs). Previously, we were able to show that rosuvastatin augments amount and functional capacity of CPCs in pts with CHF, which was associated with a correction of endothelial dysfunction. Aim of the present study was to elucidate, whether these effects are long standing and outlast the active treatment period. 42 pts with CHF (LVEF 30 ± 1 %) were randomized to 12 weeks of 40 mg rosuvastatin daily or placebo therapy in a double-blind manner followed by a 4 weeks washout period. At begin, 12 and 16 weeks, acLDL/lectin+ CPCs were recovered from blood-derived mononuclear cells by cell culture and counted using FACS. Functional capacity of CPCs was determined by matrigel assay. Flow-mediated dilatation (FMD) of the radial artery was assessed by high resolution ultrasound. The rosuvastatin mediated decrease in LDL cholesterol levels by − 56 ± 2% (from 3.7 ± 0.2 mmol/L at begin to 1.6 ± 0.1 mmol/L at 12 weeks, p < 0.05 vs. placebo) completely disappeared after the washout period (3.6 ± 0.1 mmol/L). Rosuvastatin increased CPC number by +224 % (p = 0.04 vs. placebo), four weeks after treatment cessation the number returned to initial values. The ability of CPCs to integrate into endothelial networks rose from 1.6 ± 0.4 to 2.9 ± 0.5 cells per 100 coronary endothelial cells (p < 0.05 vs. placebo for change) in response to rosuvastatin and declined to 1.5 ± 0.3 cells per 100 coronary endothelial cells after washout. FMD improved in the rosuvastatin group from 6.7 ± 1.0 % at begin to 17.7 ± 2.5 % after 12 weeks (p < 0.05 vs. placebo) and returned to 7.5 ± 2.0 % after cessation of treatment. All of the above-mentioned parameters remained virtually unchanged during the study period in the placebo group. Treatment with rosuvastatin augments the regenerative capacity of circulating endothelial progenitor cells, which might contribute to the correction of endothelial dysfunction in pts with CHF. However, 4 weeks after cessation of treatment, all these beneficial effects are completely gone, indicating the importance of long-term therapy to obtain a prognostic cardiovascular benefit.