Heart rate variability in patients with arterial hypertension associated with ischemic heart disease during treatment with calcium channel blockers

Abstract

Introduction. Significant progress in the treatment of arterial hypertension (AH) and ischemic heart disease (IHD) is associated with the discovery of third-generation dihydropyridine calcium antagonists (CA) such as amlodipine and lercanidipine. These drugs are metabolically neutral, effective, possess organoprotective properties, and have a positive impact on the outcomes of AH. It is known that, in high-risk patients, therapy also depends on its effect on heart rate variability (HRV). Despite the high clinical relevance of this problem, only a limited number of studies have been dedicated to it. Among CA, amlodipine and lercanidipine remain the most widely used. Aim of the study. To investigate the effects of amlodipine and lercanidipine on HRV in patients with AH associated with IHD and preserved left ventricular systolic function. Materials and methods. The study included 50 patients with AH associated with IHD who received treatment with amlodipine or lercanidipine. HRV and its dynamics under therapy were evaluated by changes in time and spectral parameters: SDANN, SDNN-1, RMSSD, pNN50, VLF, LF, HF, LFn, HFn, LF/HF. Results. Analysis of time and spectral HRV parameters revealed that, before treatment, the greatest prevalence of total power (TP) of heart rhythm fluctuations was observed in the group of patients compared. The most significant changes in TP were noted under ACE inhibitor therapy: TP decreased 2.1-fold, while only minor changes were observed with amlodipine. Divergent changes were identified in nLF and nHF. Nighttime and average daily nLF values were significantly lower with amlodipine (1.3-fold decrease), whereas nHF increased 2.1-fold at night (p<0.05) and 1.5-fold during the day (p<0.05). Such balancing of autonomic dysfunction under amlodipine therapy may deepen the understanding of its hemodynamic effects. When analyzing vagal influences during the day, a significant intergroup difference in HF levels was found during treatment. At night, HF was 1.9-fold higher (p<0.05) in the lercanidipine group, while in the ACE inhibitor group, HF elevation was mainly observed during the day. Similarly, LF also increased in the lercanidipine group, with a significant rise during the daytime (611.4±108.2 vs. 477.7±140.2 in the ACE inhibitor group; p<0.05). The predominance of vagal activity at night in the lercanidipine group was supported by an increase in RMSSD (1.8-fold; p<0.05) and a 15.1-fold rise in pNN50% (p<0.05) compared with the ACE inhibitor group. SDNN also increased 1.3–1.4-fold both during the day and at night. These findings suggest that lercanidipine enhances parasympathetic activity more strongly than amlodipine. Conclusions. Thus, during amlodipine therapy, an increase in the neurohumoral VLF component and the highest LF values among the comparison groups indicate the predominance of sympathetic influences of the autonomic nervous system. The relatively high HF helps to balance autonomic dysfunction. In patients receiving lercanidipine, HF during sleep was 1.9 times higher (p<0.05), whereas in the ACE inhibitor group HF elevation was mainly observed during the daytime. The predominance of vagal activity at night in the lercanidipine group was supported by an increase in RMSSD (1.8-fold; p<0.05) and a 15.1-fold rise in pNN50% (p<0.05) compared with the ACE inhibitor group. A significant increase in LF was also noted during the daytime. SDNN increased both during the day (1.3-fold) and at night (1.4-fold). Such enhancement of vagal activity during lercanidipine therapy indicates stronger parasympathetic influences induced by this calcium antagonist. Both compared calcium antagonists improve HRV: amlodipine mainly through sympathetic activity, while lercanidipine through parasympathetic activity. Amlodipine therapy is characterized by sympathetic predominance, accompanied by an increase in the neurohumoral VLF component and LF against the background of relatively high HF. In contrast, lercanidipine enhances vagal activity both during the day and at night, which demonstrates its greater efficacy in correcting autonomic imbalance under conditions of reduced parasympathetic activity, especially in patients with concomitant type II diabetes mellitus.