Effect of statin therapy on resting sympathetic nerve activity and oxidative stress in patients with heart failure

Sympathetic overactivity is well characterized in heart failure (HF) patients and is associated with increased morbidity and mortality making the sympathetic nervous system a putative drug target in the treatment of HF. Studies in rabbits with pacing induced HF have shown that statin therapy reduces sympathetic outflow potentially via a reduction in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF is unknown. We hypothesized that statin therapy reduces sympathetic nerve activity (SNA) and ROS in HF patients. Five HF patients (NYHA class I‐III; ejection fraction 23±6%; age 49±4 yrs; body mass index 30±2 kg/m 2 ) were treated with placebo or simvastatin (40 mg/day) for one month in a double blind randomized crossover design. Muscle SNA (microneurography), blood pressure, cholesterol, total ROS and superoxide levels (electron spin resonance) were measured. Statin therapy reduced resting muscle SNA in four (64±6 placebo vs. 46±7 statin bursts/100 heart beats; P<0.05) of the five patients. Likewise, total ROS and superoxide were reduced by 20±3% and 35±10%, respectively with statin therapy (P<0.05 vs. placebo). Blood pressure was unchanged and as expected, cholesterol was reduced. These preliminary findings indicate that statin therapy reduces resting muscle SNA with associated decreases in total ROS and superoxide in HF patients. Supported by NIH HL 038690‐22