Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease
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.
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Patients
Forty consecutive patients (28 men and 12 women) with a median age of 61 (range 17–70) years were studied. Twenty patients with stable CAD and 20 without CAD were recruited. The inclusion criteria were hypercholesterolaemia (LDL>200 mg/dl), positive exercise tolerance test (ETT) for the CAD(+) patients, negative ETT for the CAD(−) ones, and age<70 years. The exclusion criteria were diabetes mellitus, presence of other systemic disease(s), atrial fibrillation, and bundle branch block. All
Concomitant treatment
No other hypolipidaemic drug, besides atorvastatin, was administered during the 2-year follow-up. Most of CAD(+) patients were receiving concomitant treatment: 16 were on aspirin, 15 on a β blocker, and six on an ACE inhibitor. The regimen for each patient was established at least 6 months prior to enrollment and was maintained throughout the 2-year follow-up without any change in drug dosage.
Baseline data
At baseline, lipid parameters of both patient subgroups (CAD(−) and CAD(+)) were significantly
Discussion
The results of the present study demonstrated for the first time that therapy with a statin increased HRV level in patients with hypercholesterolaemia, with or without CAD. These changes in HRV indices may predict a beneficial effect of atorvastatin on autonomic function. The latter might contribute to a decline in cardiovascular morbidity and mortality in such patients and might be a possible mechanism, at least in part, for the reduction in clinical events reported by the landmark survival
Acknowledgements
No company or institution other than the Hippocration Hospital has financed this study.
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