Abstract
Interests about the fine underpinnings of cardiovascular beat-by-beat variability have historical roots. Over the last decades, various aspects of the relationships between arterial pressure and heart period were taken as a proxy of the baroreflex in physiology and medicine, stimulating the interest of investigators in several interconnected scientific fields, in particular, bioengineering, neurophysiology, and clinical medicine. Studies of the overall system facilitated the emergence of a simplified negative (vagal) feedback model of the baroreflex and overshadowed the simultaneous interaction with excitatory, sympathetic positive-feedback mechanisms that would, however, better suit the model of a “paired antagonistic (parasympathetic/sympathetic) innervation of the internal organs.” From the bioengineering side, the simplicity of obtaining the series of subsequent RR intervals stimulated the analysis of beat-by-beat variations, providing a multitude of heart rate variability (HRV) indices considered as proxies of the underlying sympatho-vagal balance, and participating to the management of several important clinical conditions, such as hypertension. In this context, advanced statistical methods, used in an integrated manner and controlling for age and gender biases, might help shed new light on the relationship between cardiac baroreflex, assessed by the frequency domain index α, and the HRV indices with the varying of systolic arterial pressure (SAP) levels. The focus is also on a novel unitary Autonomic Nervous System Index (ANSI) built as a synthesis of HRV considering its three most informative proxies [RR, RR variance, and the rest-stand difference in the normalized power of low-frequency (LF) variability component]. Data from a relatively large set of healthy subjects (n = 1154) with a broad range of SAP [from normal (nNt = 778) to elevated (nHt = 232)] show that, e.g., α and ANSI significantly correlate overall (r = 0.523, p < 0.001), and that this correlation is lower in hypertensives (r = 0.444, p < 0.001) and higher in pre-hypertensives (r = 0.618, p < 0.001) than in normotensives (r = 0.5, p < 0.001). That suggests the existence of curvilinear “umbrella” patterns that might better describe the effects of the SAP states on the relationships between baroreflex and HRV. By a mix of robust, non-parametric and resampling statistical techniques, we give empirical support to this study hypothesis and show that the pre-hypertensive group results at the apex/bottom in most of the studied trends.
Highlights
Since seminal studies by Sayers (1973) and Akselrod et al (1981) a few decades ago it became clear that beat-bybeat oscillations in RR interval [usually alluded to as heart rate variability (HRV; Task Force of the European Society of Cardiology and the North American Society of Pacing, and Electrophysiology, 1996)] contain hidden information on underlying neural control mechanisms, based on the instantaneous balance between parasympathetic and sympathetic mechanisms (Malliani et al, 1991)
Even a simple cursory look at available literature, it appears that HRV may spark interest for different reasons, i.e., biological and technical, alone or combined, risking to favor debates about semantics rather than substance (Brown, 2017): (1) First of all semantics: HRV is frequently used interchangeably with RR V
Descriptive data concerning the original ANS proxies and Autonomic Nervous System Index (ANSI) are given in Table 4 as means and standard deviations computed over the whole set of subjects and within the three systolic arterial pressure (SAP) groups
Summary
Since seminal studies by Sayers (1973) and Akselrod et al (1981) a few decades ago it became clear that beat-bybeat oscillations in RR interval [usually alluded to as heart rate variability (HRV; Task Force of the European Society of Cardiology and the North American Society of Pacing, and Electrophysiology, 1996)] contain hidden information on underlying neural control mechanisms, based on the instantaneous balance between parasympathetic and sympathetic (inhibitory, excitatory) mechanisms (Malliani et al, 1991). Central structures (such as the recently highlighted Central Autonomic Network – Benarroch, 1993) coordinate and govern a number of nuclei exiting in a continuous flow of inhibitory and excitatory activity regulating the (sympatho-vagal) balance, eventually determining hemodynamic performance. In physiological conditions at rest vagal activity prevails over sympathetic activity (White and Raven, 2014), approximately 4:1, and during activation, such as with exercise, the relationship is reversed, but even at maximal stimulation some level of vagal activity remains
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