Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(3): 234-239

Research Article

10.5455/NJPPP.2025.v15.i3.3

Comparison of multiscale entropy analysis of heart rate variability in young normotensive adults with and without parental history of hypertension

R. Durai Arasan^*

Department of Physiology, Velammal Medical College, Madurai, India

*Corresponding Author: R. Durai Arasan. Department of Physiology, Velammal medical college, Madurai, Tamilnadu, India. Email: duraiarasanravi [at] gmail.com

Submitted: 11/09/2024 Accepted: 13/02/2025 Published: 31/03/2025

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Abstract

Background: The autonomic nervous system (ANS) plays an essential role in regulating cardiovascular functions. Heart rate variability (HRV) refers to the variation in the time intervals between consecutive heartbeats. It serves as a non-invasive marker of ANS activity. ANS dysfunction, which can be identified by HRV, can manifest as hypertension.

Aim: The aim of this study is to compare HRV values between normotensives with and without parental history of hypertension.

Methods: The study was conducted on 60 normotensives with a history of parental hypertension and 60 subjects without history of parental hypertension in the age range 30–40 years. Subjects with normal sinus rhythm, without any systemic illness, non-smokers, and non-alcoholics were selected. HRV was measured after 5 minutes of rest for 15 minutes. Multiscale entropy analysis was employed and a p value of < 0.05 was considered statistically significant.

Results: Normotensives with a parental history of hypertension exhibited diminished short-term and long-term HRV adaptability, indicating autonomic imbalance characterized by increased sympathetic activity and reduced parasympathetic modulation. This reveals significant reductions in HRV complexity across temporal scales in the experimental group.

Conclusion: The results reflect diminished autonomic flexibility and reduced ability to respond to environmental or physiological demands among normotensives with parental history of hypertension. This could predispose those individuals to hypertension and cardiovascular risks despite normal blood pressure levels.

Keywords: Heart rate variability, Hypertension, Parental history of hypertension, Multiscale entropy analysis of HRV.

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Introduction

Autonomic nervous system (ANS)

The human ANS is a crucial component of the nervous system that manages involuntary processes in the body, such as heart rate, digestion, and breathing. It functions automatically, without conscious effort, and is divided into three main components: sympathetic, parasympathetic, and enteric nervous systems. The sympathetic nervous system is responsible for the body’s emergency response, preparing it to react to stress by increasing heart rate and respiration and decreasing activities such as digestion. In contrast, the parasympathetic nervous system (PNS) generally counters these effects, promoting rest and recovery. These systems work together to maintain a balance known as homeostasis, which regulates vital bodily functions based on changing needs. Additionally, the enteric nervous system, which governs digestive processes, is considered an ANS. These networks collectively ensure the body’s internal systems remain stable and efficient in response to external conditions (Mancia and Grassi, 2014).

Hypertension and ANS

The ANS plays an essential role in regulating cardiovascular functions, such as heart rate, vasoconstriction, and blood pressure. The sympathetic nervous system (SNS) increases the heart rate and constricts blood vessels, raising blood pressure during stress or physical activity. Conversely, the PNS lowers heart rate and induces vasodilation, reducing blood pressure and promoting relaxation (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996). This dynamic balance between the SNS and PNS is critical for maintaining normal blood pressure levels.

Hypertension is a condition where blood pressure consistently exceeds evidence-based cutoffs, generally defined as systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg, according to the American Heart Association (AHA) guidelines (Whelton et al., 2018). It is associated with significant complications, including cardiovascular diseases, cerebrovascular accidents, and end-organ damage, if left unmanaged. One of the key underlying factors in the pathogenesis of hypertension is autonomic imbalance, characterized by an altered relationship between the SNS and PNS (Thayer and Lane, 2019).

In individuals with hypertension, autonomic imbalance often manifests as heightened sympathetic activity and reduced parasympathetic activity, leading to sustained increases in heart rate, vascular resistance, and blood pressure. Studies have shown that sympathetic overactivity in hypertension can contribute to vascular remodeling, where blood vessel walls thicken, further elevating blood pressure. Simultaneously, reduced parasympathetic tone fails to counteract these effects, perpetuating chronic hypertension (Tobaldini et al., 2013).

Several mechanisms underlie autonomic imbalance in hypertension. Chronic stress is a primary contributor, continuously activating the SNS and maintaining the body in a heightened state of arousal. Other factors, such as obesity, sedentary lifestyle, and poor dietary habits, also play significant roles in autonomic dysregulation (Tentolouris et al., 2008). Effective management of hypertension often involves strategies to restore autonomic balance, such as lifestyle modifications—including regular exercise, weight loss, and stress management techniques—and pharmacological interventions. For instance, beta-blockers reduce SNS activation, whereas angiotensin-converting enzyme inhibitors promote vascular relaxation, both contributing to lower blood pressure (Grassi, 2021).

Heart rate variability (HRV)

HRV refers to the variation in the time intervals between consecutive heartbeats, measured in milliseconds. It serves as a non-invasive marker of ANS activity, particularly reflecting the balance between the sympathetic and parasympathetic branches (Shaffer and Ginsberg, 2017).

A higher variability of heart rate signifies a healthy, adaptable cardiovascular system with robust parasympathetic activity, generally associated with good physical fitness, lower stress levels, and overall better health (Draghici and Taylor, 2016; Ernst, 2017). Conversely, a lower HRV indicates sympathetic predominance and is often observed in individuals with high stress, anxiety, fatigue, or cardiovascular conditions (Siepmann et al., 2022; Yugar et al., 2023).

HRV has been studied in various populations, revealing its potential as a prognostic tool for cardiovascular health. However, there is a paucity of research focusing on HRV in young, normotensive adults with a parental history of hypertension. This gap is critical, as identifying early autonomic changes in such individuals may provide insights into pre-emptive strategies for hypertension prevention (Muralikrishnan et al., 2011).

Rationale for the study

Previous studies have highlighted the role of autonomic imbalance in hypertension and the utility of HRV as a diagnostic tool. However, most studies have focused on hypertensive individuals or older populations. The rationale for this study is to investigate autonomic function in young, normotensive adults with a parental history of hypertension. By addressing this gap, the study seeks to enhance understanding of the preclinical changes associated with hypertension risk, ultimately contributing to preventive healthcare strategies (Hamer et al., 2009).

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Materials and Methods

Study participants

A total of 120 normotensive subjects were selected from the non-communicable disease Clinic at Coimbatore Medical College Hospital, aged between 30 and 40 years, 60 subjects with a parental history of hypertension and 60 subjects without a parental history of hypertension, after obtaining approval from the Institutional Human Ethics Committee. Hypertension is defined as a condition where blood pressure is persistently elevated beyond normal levels, with SBP ≥130 mmHg or DBP ≥80 mmHg, according to the American College of Cardiology and AHA guidelines (American College of Cardiology, 2021). The sample size was calculated based on previous studies, with a minimum required sample size of 105 participants (Costa et al., 2005; Shah et al., 2020). However, to ensure sufficient statistical power, a final sample size of 120 participants was chosen. A detailed history of the participants’ parental history of hypertension was collected. The parental history and medical records were confirmed with medical records provided by the hospital as well as the records carried by the subjects.

Two separate measures of blood pressure recordings were taken for the subjects on two different occasions to confirm normotension. This was confirmed in the medical records provided by the hospital. Only subjects with normal sinus rhythm, no history of systemic illnesses, and who were non-smokers and non-alcoholics were include. Participants with a history of diabetes mellitus, hypertension, thyroid disorders, cardiac disorders, respiratory disorders, or who had a history of drug intake that could affect the ANS were excluded. Additionally, subjects were advised to refrain from exercise and the consumption of caffeinated beverages prior to the study. All the above-mentioned criteria were confirmed from both the subjects’ medical records they carried as well as the records from the hospital.

Measurements

Informed written consent was obtained from all subjects. Electrocardiogram (ECG) was performed to confirm sinus rhythm. Subjects were selected and their blood pressure and ECG were taken around 08.00 am to 10.00 am to avoid any bias arising due to diurnal variation in blood pressure. Subjects were asked to sit in a relaxed state for 15 minutes. Then, heart rate analysis was performed using HRV electrodes with the Kubios software for over 15 minutes. The recorded data were then processed with HRV analysis software from PhysioNet, and multiscale entropy (MSE) analysis was done.

Table 1. Multiscale entropy analysis of heart rate variability of normotensives with and without parental history of hypertension.

Fig. 1. Multiscale entropy analysis of heart rate variability of normotensives with and without parental history of hypertension.

Statistical analysis

To assess HRV with a focus on complexity, MSE analysis was performed. An MSE quantifies the degree of irregularity or unpredictability in physiological signals over multiple temporal scales. HRV time-series data from each subject were coarse-grained into multiple scale factors (1–20) by averaging successive points. Sample entropy (SampEn) was calculated for each scale to evaluate the complexity of the data at different levels. Entropy profiles were constructed for both groups of normotensives (with and without parental history of hypertension), showing how complexity varied across scales. Group differences in entropy were assessed using mean entropy values at small scales (1–5) and larger scales (6–20) (Goldberger et al., 2000). p < 0.05 are taken as statistically significant.

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Results

The MSE analysis provided detailed insights into group differences in HRV complexity.

Small scales (1–5): The experimental group showed lower entropy values compared to the control group (mean ± SD: 1.8 ± 0.2 vs. 2.4 ± 0.3, respectively; p=0.01). This suggests a reduced short-term adaptability of the autonomic system.

Larger scales (6–20): A similar pattern emerged, with the experimental group demonstrating consistently lower entropy values (1.5 ± 0.1) than the control group (1.9 ± 0.2; p=0.03). This indicates diminished long-term complexity in HRV signal (Table 1; Fig. 1).

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Discussion

The results of this study provide evidence that MSE analysis can uncover significant alterations in HRV complexity across different temporal scales, offering new insights. The reduced entropy observed in the normotensives with parental history of hypertension at both small and larger scales suggests a decrease in the adaptability and dynamic range of the ANS. This finding highlights the sensitivity of MSE in detecting subtle changes in HRV that may not be evident through traditional metrics.

HRV is widely recognized as a biomarker of autonomic function and cardiovascular health. Complexity in HRV, as measured by MSE, reflects the system’s ability to adapt to internal and external stressors. Healthy systems tend to exhibit high entropy, indicating robust adaptability and efficient homeostasis. In contrast, lower entropy is often associated with pathological conditions, including chronic stress, heart failure, and diabetes (Thayer and Lane, 2000). The study’s findings reveal significant differences in HRV between normotensive individuals with and without a parental history of hypertension. The normotensives who were with parental history of hypertension showed lower entropy at small scales suggesting an impaired short-term variability, often linked to parasympathetic withdrawal or increased sympathetic dominance. Such autonomic imbalance has been reported in conditions such as hypertension and myocardial infarction (Wee et al., 2020).

The decline in entropy at larger scales further demonstrates a loss of complexity over longer-term physiological fluctuations. This pattern aligns with studies showing that reduced complexity at macro-temporal levels correlates with poorer outcomes in conditions such as sepsis and heart disease (Wee et al., 2020). By using MSE, this study highlights a dynamic perspective on HRV, moving beyond the traditional focus on linear measures to incorporate the non-linear and multi-scale nature of autonomic regulation (Mäkikallio et al., 1999).

Lower MSE values in the experimental group (those with a parental history of hypertension) indicate reduced autonomic adaptability. These results suggest an impaired autonomic regulation, characterized by diminished parasympathetic activity and heightened sympathetic dominance, even in the absence of hypertension (Borovac et al., 2020).

This reduced complexity in HRV highlights a potential early marker of autonomic dysfunction, which may predispose normotensives with a family history of hypertension to future cardiovascular risks. This could lead to adverse cardiovascular effects as many findings from existing literature indicate that autonomic imbalance, often detected through lower HRV, is associated with adverse cardiovascular conditions (Sessa et al., 2018).

This observation aligns with the hypothesis that genetic predisposition to hypertension influences the ANS’s functional dynamics, even before clinical hypertension manifests (Santa-Rosa et al., 2018). The reduction in HRV complexity at both short-term and long-term scales supports the notion that autonomic imbalance could be an intermediary phenotype linking genetic predisposition and the development of hypertension (Yugar et al., 2023).

Implications and recommendations

The findings underscore the importance of early identification of autonomic dysregulation in individuals with a family history of hypertension. Proactive interventions such as lifestyle modifications—regular physical activity, stress management techniques such as yoga and meditation, and dietary changes—could potentially enhance parasympathetic activity and restore autonomic balance. These measures could potentially mitigate the risk of hypertension and associated cardiovascular complications in predisposed individuals (McManus and Zimetbaum, 2007).

Healthcare providers could also consider integrating HRV analysis, particularly advanced metrics such as SE, into routine screening protocols for individuals at risk. Such approaches may enable early detection of subtle autonomic dysfunction and guide personalized preventive strategies (Malik and Camm, 1995).

Future directions

While this study provides valuable insights, it also highlights the need for further research. Longitudinal studies are necessary to explore whether the observed autonomic changes in normotensives with a parental history of hypertension progress to overt hypertension. In addition, investigating the impact of targeted interventions on HRV complexity in this population will provide evidence for effective prevention strategies. Expanding the sample size and including diverse populations could improve the generalizability of the findings. Incorporating other biomarkers of autonomic function alongside HRV, such as baroreflex sensitivity, may also provide a more comprehensive understanding of autonomic dysregulation.

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Acknowledgment

Nil.

Conflict of interest

There are no conflicts of interest.

Funding

Nil.

Authors’ contributions

Nil.

Data availability

The data supporting this study are not publicly available due to ethical and privacy but can be obtained from the corresponding author upon reasonable request and with appropriate permissions.

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