Principal Connection Between Typical Heart Rate Variability Parameters as Revealed by a Comparative Analysis of Their Heart Rate and Age Dependence

Heart rate (HR) is strongly affected by the autonomic nervous system (ANS), while its spontaneous fluctuations, called heart rate variability (HRV), report about the dynamics of the complex, vegetative regulation of the heart rhythm. Hence, HRV is widely considered an important marker of the ANS effects on the cardiac system, and as such, a crucial diagnostic tool in cardiology. In order to obtain nontrivial results from HRV analysis, it would be desirable to establish exact, universal interrelations between the typical HRV parameters and HR itself. That, however, has not yet been fully accomplished. Hence, our aim was to perform a comparative statistical analysis of ECG recordings from a public database, with a focus on the HR dependence of typical HRV parameters. We revealed their fundamental connections, which were substantiated by basic mathematical considerations, and were experimentally demonstrated via the analysis of 24 h of ECG recordings of more than 200 healthy individuals. The large database allowed us to perform unique age-cohort analyses. We confirmed the HR dependence of typical time-domain parameters, such as RMSSD and SDNN, frequency-domain parameters such as the VLF, LF, and HF components, and nonlinear indices such as sample entropy and DFA exponents. In addition to shedding light on their relationship, we are the first, to our knowledge, to identify a new, diffuse structure in the VHF regime as an important indicator of SNS activity. In addition, the demonstrated age dependence of the HRV parameters gives important new insight into the long-term changes in the ANS regulation of the cardiac system. As a possible molecular physiological mechanism underlying our new findings, we suggest that they are associated with Piezo2 channel function and its age-related degradation. We expect our results to be utilized in HRV analysis related to both medical research and practice.