The potential role of short-term heart rate variability tests in identifying risk of hypertension in normotensive offspring of hypertensive parents

Sudipta Saha; Mahesh S Karandikar; Arunima Chaudhuri; Sibaprakash Mukherjee; Soumya Sarkar

doi:10.4103/1319-6308.149543

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ORIGINAL ARTICLE

Year : 2015 | Volume : 15 | Issue : 1 | Page : 62-67

The potential role of short-term heart rate variability tests in identifying risk of hypertension in normotensive offspring of hypertensive parents

Sudipta Saha¹, Mahesh S Karandikar¹, Arunima Chaudhuri², Sibaprakash Mukherjee¹, Soumya Sarkar¹
¹ Department of Physiology, Padmashree Dr. D Y Patil Medical College, Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
² Department of Physiology, Burdwan Medical College and Hospital, Burdwan, India

Date of Web Publication

19-Jan-2015

Correspondence Address:
Arunima Chaudhuri
Burdwan Medical College and Hospital
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1319-6308.149543

Abstract

Background: Hypertension is one of the leading causes of cardiovascular death and is primarily silent as there is hardly any symptom before target organ damage. Heredity and autonomic nervous system play pivotal roles in pathogenesis of essential hypertension. Aims: To detect early cardiovascular autonomic changes by heart rate variability (HRV) before overt hypertension, among the offspring having family history of essential hypertension. Materials and Methods: 34 normotensive offspring aged 19-24 years with parental history of essential hypertension were included as study group and the control group included 32 age, sex, and body mass index (BMI) matched normotensive offspring having normotensive parents. Resting pulse, blood pressure, and short-term supine HRV was recorded initially followed by standing HRV. Results: A statistically significant increase in resting diastolic blood pressure in study group indicated increased sympathetic tone. Postural stress in the study group revealed a greater increase (P < 0.0001) in low frequency (LF) spectrum and simultaneous greater decrease (P < 0.0001) in high frequency (HF) band as compared to control group (P < 0.05). These findings indicate greater dysfunction in both autonomic branches associated with alterations in baroreflex function in the study group. Conclusions: Current study provides an evidence of early impairments in autonomic cardiovascular regulation in young adults having hereditary history of hypertension. Early lifestyle modification with sports activity may help in improving autonomic functions and thus decrease morbidity and mortality due to cardiovascular diseases.

Abstract in Arabic

الدور المحتمل لاختبارات سرعة القلب ــ على المدى القصير ــ في تحديد خطر ارتفاع الدم بسبب ارتفاعه عند الوالدين.
خلفية: يعدّ ارتفاع ضغط الدم أحد أسباب الوفيات بسبب اعتلال القلب و الأوعية الدموية، و قد لا يشعر المريض بأية أعراض قبل تلف القلب أو الأوعية الدموية. وتؤدي الوراثة والجهاز العصبي الارادى أدوارا محورية في الإصابة بارنفاع ضغط الدم الأساسي.
أهداف الدراسة: كان هدف هذه الدراسة الكشف المبكر للتغييرات غير الإرادية في القلب والأوعية الدموية التي تؤدي إلى تفلب في معدل ضربات القلب قبل ارتفاع ضغط الدم مع وجود تاريخ عائلى للإصابة بمرض ارتفاع ضغط الدم.
المواد و منهج الدراسة: تم اختيار مجموعة الدراسة من 34 من الشباب ترواحت أعمارهم بين 19 - 24 عاما أصيب والداهم بارتفاع ضغط الدم الأساسي. واختيرت المجموعة الضابطة من 32 لم يصب والداهم بارتفاع ضغط الدم الأساسي. مع أخد العمر والجنس ومؤشرات كتلة الجسن في الحسبان. وقد سجلت معدلات النبض بعد الجهد، وضغط الدم، والنبض في وضع الاسترخاء لمدة قصيرة، متبوعا بمعدل النبض في وضع الوقوف.
النتائج: أظهرت نتائج الدراسة زيادة ملحوظة في ضغط الدم الانبساطي في مجموعة الدراسة وزيادة كبيرة في الإجهاد الوضعي في الترددات المنخفضة وانخفاضا في الترددات العاليةP< 0.0001 مقارنة بالمجموعة الضابطة 0.05 >P.
تشير هذه النتائج إلى وجود خلل وظيفي كبير في خصائص الجهاز العصبي الارادى ، مصحوبة بتبدل في وظيفة المنعكس الضعظي في مجموعة الدراسة.
الاستنتاجات: اولا تعطي هذه الدراسة دليلا على حالات القصور المبكرة في القلب و الأوعية الدموية في الشياب الذين لديهم تاريخ وراثى في الإصاية بضغط الدم. وثانيا ان ممارسة الرياضة البدنية قد تساعد في تحسين الوظائف المستقلة الارادية، و بالتالي انخفاضا فى معدلات الوفيات بسبب أمراض الدم و الأوعية الدموية.

Keywords: Essential hypertension, heart rate variability, noninvasive early detection, susceptible offspring

How to cite this article:
Saha S, Karandikar MS, Chaudhuri A, Mukherjee S, Sarkar S. The potential role of short-term heart rate variability tests in identifying risk of hypertension in normotensive offspring of hypertensive parents. Saudi J Sports Med 2015;15:62-7

How to cite this URL:
Saha S, Karandikar MS, Chaudhuri A, Mukherjee S, Sarkar S. The potential role of short-term heart rate variability tests in identifying risk of hypertension in normotensive offspring of hypertensive parents. Saudi J Sports Med [serial online] 2015 [cited 2023 Dec 4];15:62-7. Available from: https://www.sjosm.org/text.asp?2015/15/1/62/149543

Introduction

Cardiovascular diseases are one of the leading cause of death worldwide ^[1] and it has been estimated that 9.4 million deaths each year, or 16.5% of all deaths can be attributed to high blood pressure. ^[2] 1.5 million annual deaths from cardiovascular diseases have been estimated in India. ^[3] Prevalence of hypertension is increasing rapidly among the Indian population with increased industrialization and urbanization.

Essential hypertension accounts for more than 90% of the all cases of hypertension. ^[4] It is found to cluster in families suggesting probable genetic inheritance. Furthermore autonomic nervous system is known to play a pivotal role in cardiovascular homeostasis in essential hypertension. ^[4] Several studies utilizing invasive techniques such as muscle sympathetic nervous activity ^[5] and norepinephrine spillover ^[6] have shown that augmented peripheral sympathetic activity is discernable in normotensive subjects with a family history of hypertension.

An early diagnosis and better control can lead to prevention of 3,00,000 of the 1.5 million annual deaths from cardiovascular diseases in India. ^[3] Heart rate variability (HRV) is a noninvasive, easy to perform, reproducible, measure of autonomic cardiovascular control. ^[7],[8] Spectral analysis of heart rate variability (HRV) has already been used as a sensitive tool for quantitative assessment of autonomic dysfunction in various clinical disorders and also provides prognostic information. ^{[7],[8],[9],[10],[11]} If autonomic differences can be detected subclinically, before an elevation in blood pressure occurs, elucidation of these differences may lead to a design for early noninvasive detection of hypertension. Early identification of young individuals with a prehypertensive profile will provide an incentive for implementing and adhering to lifestyle modifications measures which may delay or prevent the onset of full-blown hypertension.

The main goal in this study was to evaluate autonomic control by means of noninvasive analysis of the fluctuations in cardiovascular responses in the form of HRV in young, adult, normotensive offspring with the parental history of essential hypertension.

Materials and methods

This cross-sectional pilot study was conducted in a time span of one year in a tertiary care hospital of India after obtaining institutional ethical clearance. Written and informed consent were taken from the subjects. A total number of 287 subjects of both sexes in the age-group of 19-24 years were screened with standard health history and parental history of essential hypertension while treatment records were also verified and history data were cross validated with telephonic interview of parents whenever required.

Inclusion criteria

Subjects were normotensive, nonobese, without any gross systemic disease and nonsmoker, and nonalcoholic. No persons were taking any sympathetic stimulant, blocker and Parasympathomimetics, or lytics. All subjects were told to abstain from caffeine-containing beverages and drugs. Females were examined during follicular phase of menstrual cycle.

Exclusion criteria

Subjects with any systemic, metabolic, or infectious disease were excluded. Females on oral contraceptives were excluded. No pregnant subject was included. None of the subjects were taking any daily exercise or practicing yoga. The control and study group were selected through stratified random sampling. Each MBBS batch consisted of 150 students and 50 students were randomly selected from 6 batches. Among them 13 refused to participate in the study. So, 287 students were administered questionnaires, history was carefully recorded, and clinical examination was done. A person blinded about the study recorded BP on three consecutive occasions and averaged them.

27 subjects were chronic smokers and 30 were alcoholic. Five subjects were hypertensive, 20 were on daily exercise regime, and 3 were practicing yoga, 22 were obese. Among these subjects only 92 were selected as others met exclusion criteria. 42 had parenteral history of hypertension. Six subjects did not turn up during the study. The ultimate "Study" group included total 34 (18 male and 16 female) normotensive subjects with at least one parent having essential hypertension. The "Control" group included total 32 (14 male and 18 female) age, sex, and body mass index (BMI) matched normotensive students with both parents were normotensive.

Pretest instructions

Subjects were instructed to avoid drugs that may alter autonomic or cardiac function 48 hours prior to test. Subjects abstained from strenuous exercise for 24 hours before the study and the smoking. Subjects were advised a restful night sleep and to report the laboratory at 10 AM after a light standard breakfast minimum 2 hours before arrival. The subjects were advised to have light dinner within 8 PM and go to bed early, and avoid stressful situations during the day before the tests were conducted. Relaxing bedtime routine, such as soaking in a hot bath or hot tub and then reading a book or listening to soothing music, was advised. They were asked to avoid caffeine (e.g. coffee, tea, and soft drinks, chocolate), nicotine (e.g. cigarettes, tobacco products), and alcohol close to bedtime. Enquiry was done regarding how they slept on the previous night as stress may alter autonomic functions.

Preparation of subject

To maintain constancy of conditions, all tests were carried out between 10 AM and 1PM with laboratory room temperature controlled at 22-24°C. Subjects were requested to empty their bladder before beginning the test to avoid any increase of sympathetic activity through bladder distension. ^[12]

Basic anthropometric measurements: Next, height and weight were recorded to the nearest 0.5 cm and to the nearest 0.5 Kg, respectively. BMI was calculated. ^[13] For Asians population the values of BMI have been reset as their body composition is different from that of the western world. ^[14] Proposed classification of weight by BMI in adult Asians: Underweight <18.5 Kg/m ² ; Normal range: 18.5-22.9 Kg/m ² ; Overweight >23 Kg/m ² ; Obese I: 25-29.9 Kg/m ² ; Obese II >30 Kg/m ² . Subjects with BMI between >18.5 to <25 Kg/m ² were included in this study as obesity is known to influence cardiac autonomic functions.

Then the subjects were advised rest in the supine position for 15 minutes before commencement of tests.

Determination of resting pulse rate and resting blood pressure: After 15 minutes of rest in supine position with normal quiet breathing, the pulse rate was determined. Systolic and diastolic blood pressure was measured.

Supine HRV

Polyrite-D [Multichannel digitized polygraph machine Model DSMP0410_ Version 2.4_Recorders and Medicare Systems Private Limited, Chandigarh, India] a short term 5 minute continuous lead II electrocardiograph (ECG) tracing was acquired in supine resting condition with quiet breathing and eyes closed and stabilized signals were stored automatically after filtering ectopic beats, artefacts, noise. Recording was subsequently analysed offline with inbuilt software to determine the short term HRV indices in frequency domain (power spectral density) and time domain. RMS proprietary algorithms for HRV recording and HRV calculation were validated with the recommended standardized guidelines of the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (1996). ^[7]

Standing HRV

Next, subject was asked to stand unaided on the ground from previous supine position with ECG leads already attached. Then another short span of 5 minute continuous lead II ECG tracing at same speed was acquired with Polyrite-D in standing position followed by subsequent analysis to determine HRV indices in frequency and time domain again.

Statistical analysis

Epi Info version 7 and Microsoft Office Excel 2007 software were used for statistical analysis. All data were presented as Mean ± SD. The level of significance between two groups was evaluated with independent sample unpaired t- test for normally distributed data and with Mann-Whitney nonparametric rank test for non-homogenous data. Whereas student's paired t- test (two tailed) were used to assess the effect of postural change on HRV parameters. Differences were accepted as statistically significant at P < 0.05.

Results

In the present study, no significant difference was found in resting pulse rate and systolic blood pressure between the study and the control groups. However, significantly increased resting diastolic blood pressure in the study group was observed.

The supine high frequency fluctuations in heart rate expressed in normalized unit (HF _nu ) was found to be slightly lower and the low frequency (LF) fluctuations in heart rate expressed in normalized unit (LF _nu ) was found slightly greater in the study group as compared to the control group. However, the difference was not significant statistically (P value = 0.39 and 0.38 respectively). LF: HF ratio in supine HRV was marginally higher in the study group than the control. The difference was, however, statistically non-significant (P = 0.51).

During active change of posture from supine to upright, the HF _nu was found to be decreased within both the control and the study groups, but the decrease was significantly greater (P < 0.0001) in the study group as compared to control group (P = 0.002). The LF _nu was found increased within both the control and the study. The rise was, however, significantly greater in study group (P < 0.0001) as compared to the control group (P = 0.002). The increase in

LF: HF was highly significant statistically in the study group (P < 0.0001) compared to control group (P = 0.01). The decrease in standard deviation of all normal to normal intervals (SDNN) induced by standing was significant statistically (P = 0.02) in the study group and insignificant in the control group (P = 0.68). Another time domain parameter root mean squared successive normal to normal differences (RMSSD) was also more significantly decreased within the study group (P < 0.0001) compared to the control group (P = 0.0003) as an effect of postural change to upright from supine.

Discussion

In the present study, significantly increased resting diastolic blood pressure in the study group [Table 1] is indicative of increased peripheral vascular resistance. According to Grassi et al., ^[15] the arterial compliance is under a pronounced tonic restraint by sympathetic influences and can be modulated in either direction by reflex or central alterations in sympathetic drive. In the present study, increased peripheral vascular resistance in the study group might be an effect of reduced arterial compliance probably triggered by enhanced sympathetic tone. The elevated peripheral resistance could also be due to reduced lumen areas and increased media-lumen ratios without an increase in cross-sectional area in resistance vessels (inward, eutrophic remodelling) which is probably due to vascular smooth muscle cell proliferation. ^[4] The vascular lumen and wall thickness, however, has not been measured here and the increased resistance could be due to decreased vascular lumen also. This would require further evaluation. An elevated sympathetic drive in the study group induces vascular smooth muscle cell proliferation by stimulating the release of various trophic factors such as transforming growth factor-β, insulin like growth factor-1 and fibroblast growth factor. ^[4] Thus probably, both an enhanced sympathetic tone and a decreased vascular lumen due to remodelling lead to increased peripheral vascular resistance.

Table 1: Comparison of age, anthropometric, and basalcardiovascular parameters between control and study
groups

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Resting HRV High frequency fluctuations in heart rate expressed in normalised unit (HF _nu ) are known to be solely parasympathetically mediated. ^{[16],[17],[18],[19]} The present resting HRV finding thus indicates a lower vagal tone in the study group as compared to control group, though this difference is insignificant. According to Akselrod et al., ^[16] the LF HRV is mediated jointly by sympathetic activity as well as parasympathetic system. Thus, an enhanced resting LF value would probably indicate increased sympathetic contribution in the study group. However, according to some other workers (Malliani et al., ^[18] Pagani et al. ^[20]) the LF heart rate oscillations were exclusively of sympathetic origin. If this is the case, our finding of higher resting LF value clearly indicates the enhanced sympathetic tone in the study group. The LF: HF ratio is an index of the sympathovagal balance modulating sinus node pacemaker activity. ^{[18],[21],[22]} The current observation of marginally higher LF: HF in the study group indicates that, the resting sympathovagal balance has shifted more in favour of sympathetic activity in the study group.

The spectral analysis of the supine short term HRV in the present study revealed an enhanced sympathetic activity coupled with less vagal tone in the normotensive offspring of hypertensive parents compared to the control group, though they were not significant statistically [Table 2].

Table 2: Comparison of short‑term supine HRV parameters between control and study groups

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Effect of postural stress on spectral and time domain of HRV

Arterial baroreceptors are more sensitive to pulsatile or phasic pressure than to constant pressure. The spectral and time domain HRV parameters were compared during the change of posture from supine to erect in both the groups for better insight and quantification of the effect of postural stress, as an index of cardiovascular reactivity or baroreceptor responsiveness to autonomic challenges.

During active change of posture from supine to upright the HF _nu was found to be decreased within both the control and the study groups due to vagal withdrawal on standing. However, the decrease in HF _nu was significantly greater in the study group as compared to control group indicating larger parasympathetic withdrawal in response to postural challenge in the study group. The LF _nu was higher within both the control and the study groups indicating the expected sympathetic activation. The rise was, however, significantly larger in study group indicating greater sympathetic response to autonomic challenge in the study group. The increase in LF: HF ratio was observed within both the control and the study groups [Table 3] probably due to altered sympathovagal balance modulating sinus node activity in response to standing which was tilted towards sympathetic overdrive. The rise was highly significant statistically in the study group compared to rise in the control group probably indicating impaired baroreceptor sensitivity (BRS) in response to postural challenge in the study group. Furthermore, in the study group there was a clear decrease in the total variance of heart period (R-R interval) reflected by diminished total spectral power, however, the difference was not significant statistically. This finding probably indicates the attenuated vagal potency of cardiac modulation consequent to impaired baroreflex sensitivity in response to postural stress in the study group. On standing total spectral power (TP) found to have increased marginally in the control group, however, it was not statistically significant. This observation might indicate normal cardiac vagal modulation consequent to intact baroreceptor sensitivity in response to postural stress in the control group.

Table 3: Comparison of HRV to estimate the effect of postural change within the both groups

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Moreover during active change of posture from supine to upright, the HRV analysis in the time domain demonstrated that the significant decrease in SDNN in the study group probably indicating significant decrease in the overall HRV (as SDNN reflects the total variance or all HRV spectrums ^[7] ) in normotensive offspring of hypertensive parents, indicative of diminished baroreflex modulation of heart period (R-R interval) in response to postural stress. Another time domain parameter RMSSD correlates with the high frequency modulation in short term HRV. ^[17] The observation of more significantly lower RMSSD coupled with more significantly reduced HF power in response to postural challenge clearly indicates diminished baroreflex modulation of heart period which further reflects poor cardiac vagal control on autonomic challenge in the study group as compared to control group.

The HRV revealed an enhanced sympathetic activity coupled with greater vagal withdrawal which was pronounced on challenge with postural stress probably due to attenuated baroreflex sensitivity among the normotensive offspring with parental history of essential hypertension. The sympathetic tone was also found to be higher in the genetically predisposed subjects.

In the present study, the continuous invasive blood pressure parameters like spectral analysis of systolic arterial pressure variability and "α- index" (an index which measures overall baroreflex gain) ^[23] could not be evaluated due to limited logistic resources. This could have been a useful inclusion to provide more insight. The arterial lumen and wall thickness measurement parameters can be included in the study to elucidate the autonomic vascular effect directly. Our observations may contribute to future deduction of the HRV indices with valid linear forecasting power in a clinical setting. Subjects with a genetic pre-disposition to hypertension and controls with no parental history might potentially shed light on early changes in autonomic function as a predictor of risk of hypertension, although scatter grams showing the distributions of HRV parameters in the two groups would potentially show that some of those at risk for hypertension actually fell within the values found in those who were not at risk while others were clearly abnormal. This is an interesting study conducted, with limited resources, which is actually the strength of the study.

Conclusions

The current study was carried out using the simple noninvasive analysis of HRV and autonomic function tests in the genetically susceptible, but normotensive individuals. Current study provides an evidence of early impairments in autonomic cardiovascular regulation in young adults having hereditary history of hypertension. Early lifestyle modification with sports activity may help in improving autonomic functions and thus decrease morbidity and mortality due to cardiovascular diseases.

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Tables

[Table 1], [Table 2], [Table 3]

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