Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease

Abstract

Low heart rate variability (HRV) level, indicative of impaired autonomic function, is associated with an increased risk of cardiovascular morbidity and mortality and is negatively affected by hypercholesterolaemia. In order to test the hypothesis that significant low density lipoprotein (LDL) cholesterol reduction after treatment with a statin will have a beneficial effect on HRV level in hypercholesterolaemic patients with or without coronary artery disease (CAD), forty consecutive patients (28 men and 12 women) with a median age of 61, range (17–70) years were studied. Twenty had stable CAD and 20 were free of CAD at baseline. Twenty healthy volunteers, of similar age and gender as the patients, were used as controls. Patients were treated with atorvastatin (20 mg/day) for 2 years. Changes in lipid parameters and HRV indices were assessed at baseline and 2 years later in all subjects. In both patient subgroups a significant beneficial change in all lipid parameters (more pronounced in the CAD+ subgroup) and a significant beneficial modification in HRV time and frequency domain indices was recorded (more pronounced in the CAD− subgroup), while lipid parameters and HRV indices remained unchanged in the control group. A correlation between LDL concentrations and most of the HRV indices was found at baseline in both patient subgroups, while no such correlation was found between values or their percent changes after hypolipidaemic treatment. These data suggest that treatment with atorvastatin improves autonomic function, as reflected by an increase in HRV level, and this may be a likely mechanism, at least in part, for the reduction in clinical events reported by the landmark survival studies with statins in primary and secondary CAD prevention. Perhaps, if this finding is confirmed by larger studies, HRV level may prove to be a useful tool for risk-stratification and treatment guide in high-risk patients with hypercholesterolaemia, regardless of CAD.

Introduction

In clinical practice indices of heart rate variability (HRV) have been proved to be good predictors of arrhythmic events, sudden death, and acute ischaemic syndromes [1], [2] suggesting that low HRV is associated with increased risk of cardiovascular morbidity and mortality. Moreover, low HRV predicts progression of coronary artery disease (CAD), providing information beyond that obtained by traditional risk markers of atherosclerosis [3] and is associated with events even in patients with stable CAD and preserved left ventricular function [4].

Hypercholesterolaemia is associated with a decreased HRV in men with [5] or without CAD [5], [6] and in patients with type 1 diabetes [7]. The data in the literature on the effect of serum cholesterol reduction on HRV level is limited and controversial. Hypolipidaemic diet leads to a moderate decrease in serum lipids, but does not affect HRV indices [8]. In antithesis, the REGRESS Study Group reported a significant reduction in HRV level (mainly time domain indices), after long-term administration of pravastatin in patients with stable angina pectoris, in comparison to placebo [9]. To date no evaluation of statin treatment effect on HRV indices in hypercholesterolaemic CAD(−) patients has been published.

The present study was based on the hypothesis that since increased total and low density lipoprotein (LDL) cholesterol concentrations are inversely related to HRV level [5], [6], a substantial reduction of these lipids with a statin might lead to a beneficial increase in HRV level.