Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure.
Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, 65212, USA.
Shekhar H
SH
Deo
James P
JP
Fisher
Lauro C
LC
Vianna
Areum
A
Kim
Anand
A
Chockalingam
Matthew C
MC
Zimmerman
Irving H
IH
Zucker
Paul J
PJ
Fadel
D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008923:Missouri; D018482:Muscle, Skeletal / Q000294:innervation*; D018384:Oxidative Stress / Q000187:drug effects*; D019821:Simvastatin / Q000627:therapeutic use*; D013318:Stroke Volume; D013481:Superoxides / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
D000975:Antioxidants; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013481:Superoxides; D002784:Cholesterol; D019821:Simvastatin