ABSTRACT
Many cardiovascular disease states are associated with autonomic dysfunction, specifically sympathetic activation and parasympathetic withdrawal. Both these autonomic derangements are independently associated with adverse prognostic outcomes. HMG CoA reductase inhibitors (statins) reduce cardiovascular mortality and morbidity when compared to placebo in subjects with proven coronary artery disease (CAD), including sudden presumed arrhythmic death. As autonomic dysfunction is associated with arrhythmogenesis, statins may be having a beneficial effect on autonomic function in these subjects. We conducted a randomised, double-blind, placebo-controlled, cross-over study examining the effect of rapid short-term lipid lowering with a statin on autonomic function in CAD patients. Ten subjects with proven CAD (8 male, 2 female; mean age 63.4 years) were randomised to receive either 80 mg atorvastatin or placebo over a 4 week period followed by a 4 week washout, then the alternative treatment for a further 4 weeks. Autonomic parameters assessed were plasma noradrenaline levels on recumbency and 80 degrees head-up tilt, cold pressor testing, and heart rate variability (HRV) analysis. Plasma noradrenaline levels were significantly reduced (p=0.050) after 20 min rest in the recumbent position, with atorvastatin compared to placebo. A nonsignificant reduction in plasma noradrenaline with atorvastatin compared to placebo was observed in the prolonged 80 degrees head-up position (p=0.207). In addition, sympathovagal balance was shifted to greater vagal predominance with atorvastatin (low-frequency/high-frequency ratio in the HRV frequency domain) when compared to placebo, p=0.06. We found that rapid lipid lowering with atorvastatin reduces sympathetic nervous system in this pilot study of CAD patients. Larger trials are required to definitively address the effects of statins on autonomic activity in these patients.