Abstract
Aim
The aim of the study was to compare heart rate variability (HRV) of newly diagnosed essential hypertensive subjects with controls.
Methods
The study was conducted on 120 hypertensive subjects and 120 controls.
Results
The time-domain measures, standard deviation of all RR intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), and percentage of consecutive RR intervals that differ by more than 50 ms (pNN50) which reflect parasympathetic activity were significantly less in hypertensive subjects. In frequency-domain measures, high frequency [HF (ms2)] and [HF (nu)], which reflects parasympathetic activity, was significantly less in hypertensive subjects while LF (nu) and LF/HF (%), which reflect sympathetic activity, were comparable between the groups.
Conclusion
These findings suggest that HRV is reduced in subjects with newly diagnosed essential hypertension and the parasympathetic dysregulation is present in the early stage of essential hypertension.
Keywords: Essential hypertension, Autonomic nervous system, Heart rate variability
1. Introduction
Hypertension is defined as a persistent elevated blood pressure of ≥140/90 mmHg. Essential (primary) hypertension is the most common type of hypertension, affecting 95% of all cases of hypertension.1 Hypertension is the most important preventable risk factor for premature death worldwide.2 It can increase the risk of cerebral, cardiac, and renal events. Subtle target-organ damage, such as left-ventricular hypertrophy, microalbuminuria, and cognitive dysfunction, takes place early in the course of hypertensive cardiovascular disease while catastrophic events, such as stroke, heart attack, renal failure, and dementia, usually happen after long periods of uncontrolled hypertension only.3 Thus, primary prevention of hypertension may reduce the overall risk of cardiovascular diseases.
Blood pressure is maintained physiologically by multiple mechanisms such as neural, hormonal, and local controls. Among them, neural control by autonomic nervous system (ANS) is the most important regulatory mechanism of blood pressure. Though hypertension is a multifactorial disease, ANS dysfunction is an important factor in the development and progression of hypertension.4
Heart rare variability (HRV) is defined as the oscillation of heart rate around the mean value. A reduction in HRV is associated with an increased risk of cardiac mortality and has been shown to predict risk for cardiac events and overall mortality.5 Studies have shown that changes in autonomic regulation of the cardiovascular system tend to occur before the manifestation of raised blood pressure.6 Therefore, HRV analysis may provide important insights into the role of the autonomic nervous system in the pathogenesis of essential hypertension.7 The purpose of this study was to compare the HRV of newly diagnosed essential hypertensive subjects with control subjects.
2. Research design and methods
2.1. Subjects
The study consisted of two groups: subjects with newly diagnosed hypertension and subjects without hypertension. Two hundred and forty male and female subjects between the age group of 30 and 50 years were recruited from the student and staff population of Nepalgunj Medical College, Banke. One hundred and twenty subjects with confirmed stage 1 hypertension (systolic pressure 140–159 and diastolic pressure 90–99), who had never been treated with a hypertensive medication for any indication, were the study group, and healthy age- and sex-matched one hundred and twenty normotensive subjects were the control group. The exclusion criteria were diabetes, secondary hypertension, obese, known history of chronic illness, and known neuropathy of any other etiology. In case of smokers and alcohol users, the subjects with the low nicotine and alcohol dependence were included.8, 9 The ethical clearance was obtained from the Ethics Committee of the College. All participants gave their written informed consent.
2.2. Clinical examination
All the subjects were subjected to clinical examination. Each participant underwent the measurement of his weight and height, recorded while wearing light indoor clothes but no shoes. Using a measuring tape, waist circumference (midway between the lower rib margin and the iliac crest) and hip circumference (the maximal circumference over the buttocks) were measured. Blood pressure was measured using standard protocol.
2.3. Heart rate variability
The ECG signals for HRV were recorded using electrocardiograph (Maestros Magic R Series) after a supine rest for 15 min. The resting ECG at spontaneous respiration was recorded for five min in supine position at chart speed 100 mm/s. From ECG, R-R intervals were measured manually with a ruler. Then these R-R intervals were saved as ASCII file. This format was readable by HRV analysis software 1.1 (Biomedical Signal Analysis Group, Department of Applied Physics, University of Kuopio, Finland). In this study, we analyzed HRV by three methods: time-domain, frequency-domain, and Poincare plot.
The time-domain analysis of HRV consisted of the standard deviation of all RR intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), and pNN50, which is the percentage of consecutive RR intervals that differ by more than 50 milliseconds.7
The frequency-domain analysis of HRV consisted of the power of high frequency (HF), (0.15–0.40 Hz); low frequency (LF), (0.04–0.15 Hz); and very low frequency (VLF), (below 0.04 Hz) power ranges.7
It has been speculated that analysis of HRV based on the methods of nonlinear dynamics might elicit valuable information for the physiological interpretation of HRV. One nonlinear method is Poincare plot. The Poincare plot is a scatter plot of the current R-R interval plotted against the preceding R-R interval. Using the method described by Brennan,10 these plots were used to extract indexes, such as length (SD2) and width (SD1) of the long and short axes of Poincare plot images.
2.4. Statistical analysis
Different anthropometric and cardiorespiratory variables were compared between the groups using Student independent t-test and data are presented as mean ± standard deviation. However, nonparametric Mann–Whitney U test was applied for comparisons of the HRV and the results are presented as median (interquartile range). A p value of <0.05 was considered statistically significant. Data were analyzed with statistical software IBM SPSS Statistics 21.
3. Results
3.1. Subject characteristics
Clinical characteristics of study participants are shown in Table 1. There was no significant difference between the groups in terms of their age, body mass index (BMI), and waist hip ratio. However, systolic blood pressure, diastolic blood pressure, pulse rate, and respiratory rate were significantly higher in hypertensive subjects compared with normotensive subjects.
Table 1.
Anthropometric variables of hypertensive and normotensive subjects.
| Variables | Male |
Female |
||
|---|---|---|---|---|
| HTN (78) | NT (60) | HTN (42) | NT (60) | |
| Age, years | 37.3 ± 0.4 | 37.9 ± 0.9 | 42.1 ± 0.6 | 42.4 ± 0.3 |
| BMI, kg/m2 | 26.7 ± 0.4 | 25.3 ± 0.2 | 24.8 ± 0.2 | 23.9 ± 0.6 |
| Waist hip ratio | 0.86 ± 0.02 | 0.84 ± 0.12 | 0.81 ± 0.17 | 0.82 ± 0.24 |
| SBP, mmHg | 148 ± 4.3 | 118 ± 0.7* | 142 ± 4.6 | 112 ± 0.8* |
| DBP, mmHg | 94 ± 6.5 | 72 ± 0.5* | 92 ± 8.7 | 71 ± 0.3* |
| Pulse rate | 94.64 ± 0.6 | 71.32 ± 0.8* | 86.22 ± 0.7 | 73.11 ± 0.2* |
| Respiratory rate | 17.12 ± 0.7 | 15.08 ± 0.6* | 18.32 ± 0.8 | 16.41 ± 0.7* |
HTN, hypertensive; NT, normotensive; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure. Results are expressed as mean ± SD.
p < 0.05.
3.2. Heart rate variability measures
3.2.1. Time-domain variables
The time-domain measures, SDNN, RMSSD, and pNN50 were significantly less in hypertensive subjects compared to normotensive subjects. Hypertensive women had higher time-domain measures compared to hypertensive men (Table 2).
Table 2.
Time-domain variables of hypertensive and normotensive subjects.
| Variables | Male |
Female |
||
|---|---|---|---|---|
| HTN (78) | NT (60) | HTN (42) | NT (60) | |
| SDNN (ms) | 22 (11–33) | 33.5 (24–37)* | 23 (12–34) | 36 (30–40)* |
| RMSSD (ms) | 14.7 (9.5–32.4) | 30.7 (24.4–41.6)* | 14.9 (9.8–32.7) | 36.7 (27.6–43.7)* |
| pNN50 (%) | 0.95 (0.00–5.5) | 10 (3.4–24)* | 0.96 (0.00–5.7) | 16.4 (4.7–27.3)* |
SDNN, standard deviation of all RR intervals; RMSSD, root mean square of differences of successive RR intervals; pNN50, percentage of consecutive RR intervals that differ by more than 50 ms. Results are expressed as median (interquartile range).
p < 0.05.
3.2.2. Frequency-domain variables
The variables analyzed in frequency-domain measures included power of LF, HF, in ms2 and normalized units (nu), and ratio of LF to HF (LF/HF). The LF power (ms2), HF power (ms2), and HF (nu) were significantly less in hypertensive subjects whereas LF (nu) and LF/HF ratio were comparable between the groups. Hypertensive women had higher HF (ms2), HF (nu) and lower LF (ms2) than hypertensive men (Table 3).
Table 3.
Frequency domain variables of hypertensive and normotensive subjects.
| Variables | Male |
Female |
||
|---|---|---|---|---|
| HTN (78) | NT (60) | HTN (42) | NT (60) | |
| LF (ms2) | 32.5 (13–86) | 131.5 (79–157)* | 31.5 (13–85) | 126 (86–235)* |
| LF (nu) | 50 (36.6–57.3) | 49.7 (40.6–69.4) | 57.6 (42–71.8) | 55 (39.2–66.9) |
| HF (ms2) | 42.5 (11–127) | 142.5 (69–188)* | 163.5 (99–188) | 182.5 (126–271)* |
| HF (nu) | 46.1 (23.9–62.8) | 59 (51.5–69.4)* | 47 (23.9–63.4) | 59.7 (50–73.9)* |
| LF/HF (%) | 0.84 (0.58–1.41) | 0.81 (0.58–1.15) | 0.83 (0.58–1.40) | 0.80 (0.56–.98) |
LF, low frequency; HF, high frequency; nu, normalized unit. Results are expressed as median (interquartile range).
p < 0.05.
3.2.3. Poincare plot of HRV
The variables analyzed in Poincare plot were SD1, SD2, and ratio of SD2 to SD1 (SD2/SD1). Both the variables were statistically less in hypertensive subjects (Table 4).
Table 4.
Poincare plot variables of hypertensive and normotensive subjects.
| Male |
Female |
|||
|---|---|---|---|---|
| HTN (78) | NT (60) | HTN (42) | NT (60) | |
| SD1 (ms) | 11.4 (6.9–24.7) | 26.2 (19.7–31.4)* | 11.2 (6.9–24.1) | 22.1 (17.5–29.8)* |
| SD2 (ms) | 29.25 (17.7–37.5) | 47.7 (34.4–56.3)* | 46.8 (29.1–54.4) | 52.1 (42.6–58.8)* |
| SD2/SD1 | 2.59 (1.14–3.04) | 1.81 (1.22–2.27)* | 4.71 (1.9–8.2) | 1.91 (1.56–2.51)* |
SD1, standard deviation perpendicular to line of entity in Poincare plot; SD2, standard deviation along the line of entity in Poincare plot. Results are expressed as median (interquartile range).
p < 0.05.
4. Discussion
The present study was designed to detect any alteration in cardiac autonomic function in subjects with newly diagnosed essential hypertension. The findings indicate predictable change in cardiac autonomic activity as measured by HRV.
Regular HRV test provides subclinical early detection of autonomic neuropathy and thereby promotes timely diagnostic and therapeutic intervention.11 Depressed levels of HRV occur in a number of pathological conditions and predict cardiovascular morbidity and mortality.12, 13 In the present study, all the time-domain measures were statistically low in hypertensive subjects. The SDNN reflects total variability and carries the strongest prognostic information in heart disease.7 The RMSSD and pNN50 correlate highly with HF power, reflecting parasympathetic modulation.14 Thus, the time-domain analysis of HRV showed decreased parasympathetic activity in hypertensive subjects.
In frequency-domain measures, HF (ms2), LF (ms2), and HF (nu) were significantly low in hypertensive subjects; however, LF (nu) and LF/HF were comparable between the groups. The HF component of HRV is equivalent to spontaneous respiratory sinus arrhythmia and is considered to represent the vagal control of heart rate.15, 16, 17 The physiological explanation of VLF alone is not well defined.7 The LF seems to be jointly contributed by both, vagal and sympathetic nerves.18 The LF/HF is considered to reflect sympathovagal balance, and acts as an indicator for the sympathetic nervous activity. The LF (nu) is also considered as marker of sympathetic nervous function.7 Thus, frequency-domain analysis of HRV indicates that hypertensive subjects have decreased cardiac parasympathetic activity but not the cardiac sympathetic activity.
The above differences between hypertensive and normotensive subjects are in accordance with previous studies on HRV regarding a small and nonsignificant increase in the LF (nu) and the LF/HF in the hypertensive group.19 However, Huikuri et al. displayed decreased LF/HF in the hypertensive subjects.13 The subjects in the study by Huikuri et al. were using vasoactive drugs at the time of the examination, which may have influenced the results.
In both hypertensive and normotensive subjects, HF was higher in women, which suggests a higher tonic parasympathetic activity in women than in men. The observed difference in heart rate dynamics between men and women could reflect a protective role of estrogen in women. The compliance of the brachial artery is higher in women than in men.20 Women have greater HRV and greater complexity of heart rate dynamics then men across a wide adult age spectrum.21 In addition, hypertensive women have less cardiovascular reactivity to stress compared with hypertensive men.22
In Poincare plot measures, SD1 and SD2 were significantly low in hypertensive subjects. Analysis of the SD2/SD1 ratio provides information on the relationship between sympathetic and parasympathetic tone. The present study showed a higher ratio in subjects with hypertension. A higher SD2/SD1 ratio may reflect an increase in SD2, a decrease in SD1, or both. A decrease in SD1 means a decrease in parasympathetic activity while a decrease in SD2 means an increase in sympathetic activity.23, 24, 25 In the present study, decrease in SD1 was greater than in SD2, so a higher ratio implies both reduced parasympathetic activity and greater sympathetic activity in subjects with hypertension.
In most studies, HRV measures have been lower in hypertensive subjects compared with normotensive subjects.19, 26, 27, 28 Investigators suggested that essential hypertension is commonly neurogenic and attributed to sympathetic overdrive; the parasympathetic branch has largely been neglected. In contrast to those studies, our study suggests that first parasympathetic withdrawal takes place in the early stage of hypertension. This is confirmed by decrease in all the markers of parasympathetic system but by either significant or nonsignificant increase or decrease in the markers of sympathetic system. Moreover, the results in essential hypertension have been inconsistent showing changes in HF and LF in opposite directions. It might be because the hypertensive subjects had never been treated with antihypertensive medication. β-Blockers have been shown to increase HF component while LF component of HRV has remained unchanged or increased.28 This also confirmed that a reduction in parasympathetic cardiac control significantly contributes to a disturbance in cardiovascular control in subjects with essential hypertension.
In clinical practice, it is not routine to assess sympathovagal balance in those with diagnosed essential hypertension, and there is no recommended clinical method on how to do so in this circumstance. However, it may be appropriate to assess HRV at an early stage in hypertension and identifying cardiovascular autonomic failure at an early stage helps in implementing appropriate interventions.
In conclusion, parasympathetic system is more involved than the sympathetic system in subjects with newly diagnosed essential hypertension. The decreased parasympathetic tone in hypertension is associated with increased sympathetic tone. We also find that women have relatively greater HRV markers that are associated with parasympathetic activity than men. This complementary finding indicates the importance of gender-related difference in heart rate dynamics. Whether reduced HRV contributes to the increased cardiac mortality in hypertension requires further study.
Conflicts of interest
The authors have none to declare.
Contributor Information
Rajesh Kumar Goit, Email: goit_rajesh@yahoo.com.
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