Potential autonomic nervous system effects of statins in heart failure

Abstract

Sympathetic nervous system activation in heart failure, as indexed by elevated norepinephrine levels, higher muscle sympathetic nerve activity and reduced heart rate variability, is associated with pathologic ventricular remodeling, increased arrhythmias, sudden death, and increased mortality. Recent evidence suggests that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy may provide survival benefit in heart failure of both ischemic and nonischemic etiology, and one potential mechanism of benefit of statins in heart failure is modulation of the autonomic nervous system. Animal models of heart failure demonstrate reduced sympathetic activation and improved sympathovagal balance with statin therapy. Initial human studies have reported mixed results. Ongoing translational studies and outcomes trials will help delineate the potentially beneficial effects of statins on the autonomic nervous system in heart failure.

Figures

Figure 1

The Kaplan-Meier estimates of arrhythmic sudden death plus resuscitated cardiac arrest among patients treated with statins and those not taking statins in the 458 patients enrolled in the DEFINITE trial. From Goldberger JJ, Subacius H, Schaechter A, et al. Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol. Sep 19 2006;48(6):1228–1233, with permission.

Figure 2

Original recording of arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in 1 conscious heart failure animal (top) and 1 conscious heart failure animal treated with simvastatin (bottom) for 3 weeks. At arrows, an injection of SNP was given intravenously. From Pliquett RU, Cornish KG, Peuler JD, Zucker IH. Simvastatin normalizes autonomic neural control in experimental heart failure. Circulation. May 20 2003;107(19):2493–2498, with permission.

Figure 3

Heart rate variability parameters in the statin and control groups at baseline and after 3 months of the study (the results are presented as mean + SD). From Vrtovec B, Okrajsek R, Golicnik A, Ferjan M, Starc V, Radovancevic B. Atorvastatin Therapy Increases Heart Rate Variability, Decreases QT Variability, and Shortens QTc Interval Duration in Patients With Advanced Chronic Heart Failure. Journal of Cardiac Failure. 2005;11(9):684, with permission.