Heart Rate Variability as a Marker of Homeostatic Level

*Moacir Fernandes de Godoy and Michele Lima Gregório*

### **Abstract**

Many variables have been used as homeostatic level markers. Heart Rate Variability (HRV) has been frequently cited as an indicator of homeostatic status. Low levels of HRV are associated with aging, disease, or increased risk of death. We present a study based on more than 10.5 million data collected from the literature, associating the degree of global clinical impairment of individuals, with their respective HRV data, seeking to establish a classification of Homeostatic Levels. Three specific variables were evaluated: heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals in a time interval (RMSSD) and the HF band (HF ms2 ). It was possible to detect significant differences between the 83,927 data from healthy individuals and the 382,039 data from individuals with significant homeostatic impairment. It was demonstrated that the RMSSD is very sensitive to the worst homeostatic state, presenting a behavior independent of age and that the values found in the general population do not match the values of apparently healthy individuals. An alphanumeric classification of the homeostatic level in a three-level architecture was proposed, with three stages for each level, which may be extremely useful in prognostic assessment and decision-making about individual people.

**Keywords:** autonomic nervous system, heart rate variability, homeostatic level

### **1. Introduction**

The human organism is a dynamic, deterministic, non-linear system that shows a sensitive dependence on initial conditions. The amount of cells in the human body is extraordinarily large. A study carried out by Eva Bianconi with collaborators from Italy, Greece and Spain, concluded with the number of 3.72 ± 0.81 × 1013, or approximately 37 trillion cells. There is already an estimate of the amount of cells that need to be removed daily in a healthy human adult, seeking to maintain the body's stability. That number reaches the extraordinary value of 150 billion cells a day! If we remember that the total amount of cells is approximately 37.2 trillion, we conclude that, per day, a healthy human individual loses 0.4% of its cell mass [1].

It is inferred, then, that for the maintenance of life through the proper, harmonious and stable functioning of these cells, in addition to the restoration of lost elements, it is mandatory to spend energy. The clinical concept that refers to this condition of maintenance of conditions of stability is Alostasia. Through Alostasia, Homeostasis is maintained.

The name Homeostasis was created by Walter B. Cannon, in 1932. Literally translated, homeostasis means "staying the same", but this is not entirely accurate. In reality, homeostasis is not a static state; rather, it is a dynamic state.

In biology, homeostasis is classical, the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits, and which we will call from now on, as the Homeostatic Level.

One of the fundamental elements for the control of the Homeostatic Level is the Autonomic Nervous System (ANS), with its different components, the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system [2].

The effects of aging on the autonomic nervous system are multiple and vary between and within both sympathetic and parasympathetic portions. Normal human aging is associated with changes in autonomic control of several bodily functions, particularly those served by cardiovascular and thermoregulatory systems [3].

The assessment of the autonomic nervous system has been possible through the quantification of a biological marker called Heart Rate Variability (HRV). The literature is extremely rich in studies on HRV, and its high applicability in terms of diagnosis and prognosis is a consensus.

It is possible to study HRV in different domains, namely time, frequency and nonlinear. In these domains, different variables have already been described, each with its greater or lesser sensitivity.

Briefly, however, we can highlight three of them among those with the greatest clinical applicability: heart rate (HR), the root-mean-square of successive differences between adjacent normal RR intervals in a time interval (RMSSD) and the HF band representing the power in the frequency range between 0.15 and 0.4 Hz (HFms2) [4].

### **2. Heart rate**

Resting heart rate has ceased to be just another vital sign and has become a relevant cardiovascular risk marker. It has long been known that life span is inversely related to resting heart rate in most organisms. The classic article by Levine [5], shows the existence of an inverse semilogarithmic relation between heart rate and life expectancy among mammals, suggesting a predetermined number of heart -beats in a lifetime, with a magic average number of 7.3 ± 5.6 × 108 heart-beats/lifetime.

Boudoulas KD et al. [6], make an excellent review relating heart rate, life expectancy and the cardiovascular system. They conclude that many factors regulate heart rate, and it may be these factors, rather than the heart rate itself, which determine survival, but heart rate has multiple direct effects on the cardiovascular system, regardless of the regulatory mechanisms. These effects directly affect the cardiovascular system in multiple ways that, in turn, may affect survival.

From a pathophysiological point of view, the main finding is that resting heart rate is associated with shear and endothelial function in humans [7].

The impact of increased resting heart rate on prognosis is validated in the general population in patients with hypertension, coronary artery disease, or heart failure and irrespective of age, cardiovascular risk factors, or comorbidities, although there is still no definitive confirmation of the prognostic effect of heart rate reduction with the use of drugs such as ivabradine, on primary combined events [8].
