Abstract 1863: Antioxidative Properties of Rosuvastatin in Patients with Chronic Heart failure: Improvement of Peripheral Vasomotor Function and Central Hemodynamics
In patients with chronic heart failure, reactive oxygen species (ROS) are known to rapidly inactivate endothelium-derived nitric oxide, which is in turn associated with an impairment of endothelial function, an increase in afterload and, consequently, a decline in ejection fraction. Based on the known antioxidative properties of statins, it was the aim of the present study to evaluate the effects of rosuvastatin treatment on oxidative stress, its impact on endothelial dysfunction and hence central hemodynamics in patients with chronic heart failure.
Methods: Forty patients with chronic heart failure (LVEF 30±1%) due to ischemic (n=12) or dilated cardiomyopathy (n=28) were randomized to 12 weeks of oral rosuvastatin (40 mg daily) or placebo treatment in a double-blind manner. At baseline and at 12 weeks, circulating levels of oxidized LDL (oxLDL) and lipid peroxides were measured as a read out of oxidative stress by ELISA. Endothelium-dependent, flow-mediated vasodilatation (FMD) of the radial artery was assessed by high resolution ultrasound. Echocardiography was applied to determine left ventricular ejection fraction.
Results: Rosuvastatin decreased oxLDL levels by −27 % (from 42.3±6.8 μmol/L at baseline to 31.0±4.7 μmol/L at 12 weeks, p<0.05 vs. placebo) and effectively reduced lipid peroxidation by −8 % (from 267±35 μmol/L at baseline to 245±39 μmol/L at 12 weeks, p<0.05 vs. placebo for the change). The rosuvastatin-mediated attenuation in oxidative stress was associated with a recovery of flow-mediated dilatation by +264% (from 6.7±1.0 % at begin to 17.7±2.5 % at 12 weeks, p<0.05 vs. placebo) and an increase in left ventricular ejection fraction by +27% (from 30±1 % at baseline to 38±2 % at 12 weeks, p<0.05 vs. placebo). All of the above-mentioned parameters remained virtually unchanged during the study period in the placebo group.
Conclusion: In patients with chronic heart failure, rosuvastatin 40 mg daily decreases oxidative stress, which is associated with a restoration of peripheral endothelial function and a partial recovery of left ventricular function.