Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(1): 15-19

Original Research

10.5455/NJPPP.2025.v15.i1.3

A comparative study of cardiac autonomic functions in normotensive individuals with and without family history of hypertension

Sandra Christina George^1*, V. H. Ahammed Naseem¹, Ajay Kumar Saran² and Nayana M. Nair¹

¹Department of Physiology, Government. Medical College Kozhikode, Kozhikode, India

²Departmentt. of Physiology, Government. Medical College Manjeri, Manjeri, India

*Corresponding Author: Sandra Christina George. Department of Physiology, Government. Medical College Kozhikode, Kozhikode, India. Email: sandra.george717 [at] gmail.com

Submitted: 05/06/2023 Accepted: 04/12/2024 Published: 31/01/2025

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Abstract

Background: Since genetic heredity accounts for 30% of blood pressure variance, it is seen that the possibility of early-onset hypertension linked to autonomic dysfunction is increased by parental history of hypertension. Hence, in the offspring of hypertensive parents, recording blood pressure alone is insufficient and requires an assessment of cardiac autonomic functions.

Objectives: To analyze the cardiovascular autonomic functions of normotensive individuals with a family history of hypertension and compare it with that of age and gender-matched controls.

Materials and Methods: A comparative cross-sectional study was conducted in Government Medical College, Kozhikode among 158 subjects (79 normotensives with a family history of hypertension and 79 age and sex-matched controls) of age group 18–30 years by simple random sampling. Ewing’s battery of cardiovascular autonomic function tests was performed and assessed using 16 channel PHYSIOLAB with PHYSIOPAC software. SPSS 25 software for Windows with Unpaired T-Test was used for statistical analysis.

Results: A significant increase in sympathetic response was observed in the study group, as compared to controls, presumably due to inherited vascular reactivity. Since autonomic responsiveness to stress serves as a predictor of neurogenic hypertension, the tilt towards sympathetic overactivity may indicate autonomic imbalance preceding the onset of hypertension.

Conclusion: An increase in sympathetic activity observed in the study group emphasizes the effect of genetic influence on hypertension. Early detection, especially in the offspring of hypertensive parents, by employing cardiovascular autonomic function tests, helps in the implementation of preventive measures that halt the progression of the disease.

Keywords: cardiovascular autonomic function tests, family history of hypertension, Ewing’s battery.

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Introduction

The Autonomic Nervous System (ANS) is the part of the nervous system that regulates and integrates the functioning of internal organs and enables the internal environment to adapt to changes in the external environment (Zygmunt and Stańczyk 2010). It serves as a major regulator of the cardiovascular system by mainly controlling the heart rate and blood pressure. Parasympathetic (vagal) modulation reduces heart rate and cardiac contractility, whereas sympathetic activity counteracts these effects and modulates peripheral vasoconstriction. A well-regulated cardiac ANS function relies on robust parasympathetic activity and efficient, although not excessive, sympathetic modulation of the heart, which is linked to a reduced risk of cardiovascular complications (Hägglund et al., 2012). There is clear evidence that it is autonomic dysfunction that triggers the onset and maintenance of hypertension (Muralikrishnan et al., 2011).

Hypertension is a chronic disease that affects about 1 billion people worldwide and adds to the burden of stroke, heart disease, kidney failure, premature death, and disability (World Health Organization 2013). According to the Global Burden of Disease Study 2019, elevated systolic pressure is ranked as the leading cause of lost years of quality life (Collaborators GBD 2019 RF 2020) with half of the American adult population suffering from hypertension, according to the 2017 guidelines of the American Heart Association (Whelton et al., 2018). In India, the overall prevalence of hypertension was found to be 29.8% with 27.6% prevalence in rural parts and 33.8% prevalence in urban parts of south India (Anchala et al., 2014). In addition, hypertension is directly to blame for 24% of all fatalities from coronary heart disease and 57% of all deaths from stroke in India (Gupta 2004).

According to the 2020 International Society of Hypertension Global Hypertension Practice Guidelines, a person can be diagnosed with hypertension if, after repeated examinations, their systolic blood pressure (SBP) in the office or clinic is ≥140 mm Hg and/or their diastolic blood pressure (DBP) is ≥90 mm Hg (Unger et al., 2020).

According to the Dual Theory of Pathogenesis of Hypertension, the fundamental hemodynamic abnormality in chronic stable hypertension is increased vascular resistance, which is caused by both increased vasoconstriction and exaggerated sympathetic activity (Abboud 1982). In the early stages of hypertension, sympathetic overactivity is exhibited as a hyperkinetic circulation that is marked by increases in heart rate, cardiac output, and plasma norepinephrine levels. This could directly encourage the development of target organ damage, like large-artery stiffness and left ventricular hypertrophy (Palatini and Julius 2009; Rafanelli et al., 2019).

Since hypertension is an outcome of the interaction of many factors which include genetic factors, environmental factors, and hypertensinogenic factors such as obesity and high alcohol and salt intake (Carretero and Oparil 2000), it is seen that hypertension runs in families, and parental history of hypertension raises the likelihood of developing hypertension, especially in conditions where both the parents are hypertensives (Wang et al., 2008). Apart from genetic factors, lifestyle factors which include physical inactivity, high-fat diet, and stress have contributed to the increased incidence of hypertension in young adults (Ahmed et al., 2016). Numerous studies, including those by McCrory et al. (1982). and Horikoshi et al. (1985) have demonstrated an increase in plasma catecholamine levels in normotensives with hypertensive parents in response to mental and orthostatic stress, thereby suggesting that the propensity for developing hypertension begins at an early age and that autonomic dysregulation may be present, even at the stages of normotension (Mancia and Grassi 2014). Hence, in those individuals with a family history of hypertension, a recording of the blood pressure alone may be insufficient and requires an assessment of the cardiac autonomic functions, which is of great prognostic value (Lopes et al., 2000; Muralikrishnan et al., 2011).

Given the complexity of the autonomic system, numerous tests are used to assess the autonomic functions, the most popular being Ewing’s test battery. They are non-invasive tests that provide a simple bedside assessment of autonomic functions and are based on the idea that heart rate responses are primarily mediated via cardiac parasympathetic pathways and blood pressure responses are controlled by sympathetic pathways (Ewing et al., 1985; Zygmunt and Stańczyk 2010).

Since regular monitoring of autonomic activity proves to be a valuable method in predicting future hypertensives (Rathi et al., 2013), early identification of these individuals will encourage them to implement and adhere to lifestyle modifications, such as weight reduction as well as starting a moderate-intensity aerobic exercise program, which provides the advantage of delaying or preventing the onset of full-blown hypertension (Davrath et al., 2003).

This study aims to determine the cardiac autonomic functions in normotensive individuals with a family history of hypertension and to compare it with normotensives with no family history of hypertension.

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Materials and Methods

This study was carried out as a comparative, cross-sectional study in the Department of Physiology, Government Medical College, Kozhikode for a period of 1 year after clearances from the Institutional Research Committee and Institutional Ethics Committee. Subjects in the age group 18–30 years were taken from among students, PG residents, and staff of Government Medical College, Kozhikode, by simple random sampling. Out of the 158 subjects included in the study, 79 were normotensives (Systolic BP 90–139 mm Hg, Diastolic BP 60–89 mm Hg) with a family history of hypertension in first-degree relatives and 79 were age and gender-matched controls. Subjects with acute illnesses, those with a history of systemic disorders/diseases that affect autonomic functions, those on medications that can alter autonomic functions, those with a history of smoking, and those involved in physical activities of any kind above routine level were omitted from the study.

After getting prior informed consent, data were collected using a standardized questionnaire which included demographic details along with detailed medical history along with dosage, duration, and type of antihypertensive therapy if family history of hypertension was present. Basal Blood Pressure, heart rate, and ECG were recorded. Cardiac Autonomic Function Assessment was done using 16 channel PHYSIOLAB with PHYSIOPAC software and by calculating the autonomic function tests and ratio by standard guidelines.

Cardiovascular autonomic function assessment (Ewing’s test battery) (Ewing and Clarke 1982)

1. Heart rate response to immediate standing (30:15 ratio)
2. Heart rate variation during deep breathing (Deep breathing test)
3. Heart rate response to Valsalva manoeuvre
4. Blood Pressure response to immediate standing
5. Blood Pressure response to sustained hand-grip (Isometric hand-grip test).

Data were analyzed using SPSS version 25 software for Windows program. Normality assessment of the data was done with the Kolmogorov–Smirnov test, for which a non-significant result (p > 0.05) indicates normality. Since the data followed normality, the unpaired T-test was the statistical test used for comparing quantitative parameters.

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Results

Resting cardiorespiratory parameters like basal heart rate and resting respiratory rate were similar in both the study groups as represented in Table 1.

Differences observed in the parasympathetic function tests between the study groups were not found to be statistically significant (p > 0.05) as shown in Table 2.

However, the sympathetic function tests showed a statistically significant difference between the two groups as depicted in Table 3. The fall in systolic blood pressure on standing is less in the normotensive group with a family history of hypertension and the rise in the diastolic blood pressure on sustained handgrip is higher as compared to the control group. These differences were found to be highly statistically significant (p < 0.001).

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Discussion

The present study aimed to assess the cardiovascular autonomic functions of normotensive individuals with a family history of hypertension and compare it with age and gender-matched controls using Ewing’s battery of tests.

Among the resting cardiorespiratory parameters, although the mean resting systolic and diastolic blood pressures were found to be higher in the normotensive group with family history of hypertension as compared to the control group, this difference was not found to be of statistical significance (p > 0.05). This shows that both the groups are normotensive at rest. These findings were analogous to those obtained in a study by Rathi et al. (2013), where the increase in resting systolic and diastolic blood pressure was found to be slightly higher in the study group, but there was no statistical significance.

Table 1. Distribution of resting cardiorespiratory parameters among the study groups.

Table 2. Distribution of parasympathetic function among study groups.

Table 3. Distribution of sympathetic function among the study groups.

Assessment of parasympathetic function tests did not show statistical significance in the difference between the two groups. While a number of studies including those conducted by Nandre et al. (2017) and Rathi et al. (2013) showed similar results while assessing the parasympathetic arm of the ANS, there were other studies by Wu et al. (2008) and Muralikrishnan et al. (2011) that showed that there was a decrease in the parasympathetic drive in the normotensive group with a family history of hypertension. However, in the study by Wu et al. (2008), from normotensives with a family history of hypertension to frank hypertensives, the degree of parasympathetic drive reduction increased over time, thereby suggesting that parasympathetic disruption is a dynamic phenomenon that may be minimal in young normotensives with a family history of hypertension.

Assessment of sympathetic function tests, however, showed a highly statistically significant difference (p < 0.001) between the two groups. These results were in concordance with those of the study by Nandre et al. (2017). whereas the study by Rathi et al. (2013). showed a significant difference between the study groups in the blood pressure response to sustained handgrip but not on standing. Studies by Karmacharya et al. (2020) and Garg (2013) which tested the blood pressure response to isometric hand grip found a significant increase in the systolic as well as diastolic pressure in normotensive offspring of hypertensive parents.

These results suggest that there is an inappropriate increase in sympathetic response to stressors like isometric handgrip in normotensives with a family history of hypertension. This test is of prognostic importance in determining sympathetic reactivity as it causes peripheral vasoconstriction mediated by adrenergic receptors of the sympathetic nervous system along with concomitant release of endothelin. Offspring of hypertensive parents have higher plasma catecholamine levels as compared to offspring of normotensive parents, which is further accentuated by this release of endothelin, and in turn alters the activity and vascular effects of the sympathetic nervous system (Karmacharya et al., 2020). As suggested in a study by Pramanik et al. (2008), stress-induced tests may be utilized as predictors of hypertension since those who respond to them more strongly and for longer periods of time are more likely to acquire hypertension (Pramanik et al., 2008).

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Conclusion

The results obtained from the study strongly suggest that even though resting cardiorespiratory parameters and parasympathetic activity appear to remain unchanged, there is a significant increase in the activity of the sympathetic nervous system in normotensive individuals with a family history of hypertension as compared to age and gender-matched controls.

The evidence of increased sympathetic activation at such an early stage of disease progression highlights the importance of genetic influence on the prehypertensive phase of hypertension and the necessity of targeting a decrease in sympathetic activation as the main objective in the prevention and treatment of hypertension (Davrath et al., 2003).

Early detection of sympathetic overactivity in offspring of hypertensive parents is gradually becoming a necessity, as it helps in implementation of lifestyle modifications like weight reduction, salt restriction as well as staring a moderate intensity aerobic exercise program, along with regular monitoring of autonomic activity, that slow the progression of the disease (American College of Sports Medicine. Position Stand. Physical activity, physical fitness, and hypertension, 1993; Rathi et al., 2013; Taler et al., 2018). Moreover, this is economically advantageous as the relative cost of testing will always be less than the costs of treating the complications that could eventually occur if left undiagnosed.

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Acknowledgments

The authors would like to acknowledge the Dept. of Physiology, Govt. Medical College Kozhikode for providing the facilities for conducting the research as well as the staff and students who participated in the study.

Conflict of interest

None.

Funding

No funding was received for conducting the study.

Authors’ contributions

Conception and Design: Sandra Christina George, Ahammed Naseem V. H; Acquisition of data: Sandra Christina George, Ajay Kumar Saran, Nayana M. Nair; Analysis and Interpretation of data: Sandra Christina George, Ajay Kumar Saran, Nayana M. Nair; Writing – original draft: Sandra Christina George; Writing – review and editing: Sandra Christina George, Ahammed Naseem V. H., Ajay Kumar Saran, Nayana M. Nair; Final approval of completed article: Sandra Christina George, Ahammed Naseem V. H., Ajay Kumar Saran, Nayana M. Nair.

Data availability

The data that support the findings of this study are available from the corresponding author on request.

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