Differential effects of lipophilic and hydrophilic statins on muscle sympathetic nerve activity in heart failure with preserved left ventricular ejection fraction

Auton Neurosci. 2018 Sep:213:8-14. doi: 10.1016/j.autneu.2018.04.006. Epub 2018 Apr 30.

Abstract

Augmented sympathetic nerve activity is associated with heart failure with preserved left ventricular ejection fraction (HFpEF). Lipophilic statins reduce sympathetic nerve activity in patients with heart failure with reduced left ventricular ejection fraction. However, little is known about whether all types of statins, regardless of solubility, reduce sympathetic nerve activity in HFpEF. We evaluated the effect of atorvastatin, a lipophilic statin, and rosuvastatin, a hydrophilic statin, on muscle sympathetic nerve activity (MSNA) in HFpEF patients. This study was conducted as a prospective, randomized, open-label, crossover trial. Ten HFpEF patients with untreated hyperlipidemia participated in this study. Subjects were assigned to either the atorvastatin (lipophilic) or the rosuvastatin (hydrophilic) group with each drug administered for 8 weeks. Atorvastatin and rosuvastatin treatment resulted in a similar reduction in low-density lipoprotein cholesterol (LDL-C) levels. There was no difference in the effect of either treatment on blood pressure, heart rate, or left ventricular function. Atorvastatin significantly decreased MSNA frequency compared with baseline (31.5 ± 6.3 vs. 47.5 ± 10.7 bursts/min, p < 0.01), but rosuvastatin had no effect on MSNA (40.9 ± 7.3 bursts/min). MSNA was significantly lower in the atorvastatin group than rosuvastatin group (p < 0.05). However, the reduction in MSNA seen in either group did not correlate with the reduction in LDL-C. No significant differences were observed in either the baroreflex control of heart rate or MSNA between the two groups. These results suggest that lipophilic statins have a favorable effect on sympathetic nerve activity beyond lowering LDL-C in HFpEF, but hydrophilic statins do not.

Keywords: Hypertension; Muscle sympathetic nerve activity; Statin.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atorvastatin / chemistry
  • Atorvastatin / therapeutic use*
  • Baroreflex / drug effects
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Heart Rate / drug effects
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Muscles / drug effects*
  • Muscles / innervation
  • Rosuvastatin Calcium / chemistry
  • Rosuvastatin Calcium / therapeutic use*
  • Solubility
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiopathology
  • Ventricular Function, Left / drug effects

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • Rosuvastatin Calcium
  • Atorvastatin