Standardized tests of heart rate variability for autonomic function tests in healthy Koreans

Heart rate variability (HRV) is a noninvasive measure of autonomic input to heart rate that has been successfully used to estimate modulation of autonomic tone. The authors investigated to determine the normal ranges as a standardized tests of heart rate variability (HRV) for autonomic function tests in a large sample of healthy Koreans. The study also evaluated the effects of age, sex, and heart rate (HR) on the results of HRV and the values of HRV in hypertension, diabetes, and obesity group. Six hundred and thirty-seven healthy subjects who visited the health improvement center for medical examination were evaluated. A standardized 5-min resting study, including spectral analysis of HR, was used to all participants after an overnight fast. HRV (SA-2000E, Medicore, Korea) was spectrally determined by three components: total-frequency (TF) component (0.01 to 0.5 Hz), low-frequency (LF) component (0.04 to 0.15 Hz), and high-frequency (HF) component (0.15 to 0.5 Hz). Also two component ratio (LF/HF) was calculated. Routine laboratory and physical examinations were used to eliminate cardiovascular diseases and neurological disorders. The determinants of short-period HRV in a random sample of 366 men and 271 women from healthy subjects were assessed. The mean age of these subjects was 45.1 +/- 10.7 years. The mean value of total power was 1106.9 +/- 1109.1 ms(2); SDNN was 35.9 +/- 15.5 ms; rMSSD was 27.3 +/- 15.6 ms for time domain analysis. The mean value of LF was 287.5 +/- 384.1 ms(2); HF was 227.0 +/- 284.4 ms(2); LF/HF was 2.2 +/- 3.4 for frequency domain analysis. Additionally, men showed that their TP, LF, and LF/HF values were significantly higher than women whereas SDNN, rMSSD, HF showed no significant differences between sexes. With increasing age, there was no significant decrease in HR. TP, SDNN, LF, and HF were significantly decreased when getting older. On the contrary, LF/HF had no significant difference related to age. The study confirmed that SDNN and rMSSD were significantly lower in hypertension and diabetes group. In conclusion, middle-aged men had more pronounced sympathetic influence than women in cardiac regulation, and HRV declined linearly with age. In addition, HRV reflecting the function of autonomic nervous system was decreased in hypertension and diabetes group.     

Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n=309). Conventional tests (deep breathing, maximum/minimum 30∶15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30∶15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middleaged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.     

Decrease in heart rate variability response to task is related to anxiety and depressiveness in normal subjects

Aims: Previous studies have shown that heart rate variability (HRV) measurement is useful in investigating the pathophysiology of various psychiatric disorders. The present study further examined its usefulness in evaluating the mental health of normal subjects with respect to anxiety and depressiveness. Methods: Heart rate (HR) and HRV were measured tonometrically at the wrist in 43 normal subjects not only in the resting condition but also during a task (random number generation) to assess the responsiveness. For HRV measurement, high‐frequency (HF; 0.15–0.4 Hz) and low‐frequency (LF; 0.04–0.15 Hz) components of HRV were obtained using MemCalc, a time series analysis technique that combines a non‐linear least square method with maximum entropy method. For psychological evaluation of anxiety and depressiveness, two self‐report questionnaires were used: State–Trait Anxiety Inventory (STAI) and Self‐Rating Depression Scale (SDS). Results: No significant relation was observed between HR and HRV indices, and the psychological scores both in the resting and task conditions. By task application, HF decreased, and LF/HF and HR increased, and significant correlation with psychological scores was found in the responsiveness to task measured by the ratio of HRV and HR indices during the task to that at rest (task/rest ratio). A positive relationship was found between task/rest ratio for HF, and STAI and SDS scores. Task/rest ratio of HR was negatively correlated with STAI‐state score. Conclusion: Decreased HRV response to task application is related to anxiety and depressiveness. Decreased autonomic responsiveness could serve as a sign of psychological dysfunction.     

STANDARDIZED TESTS OF HEART RATE VARIABILITY FOR AUTONOMIC FUNCTION TESTS IN HEALTHY KOREANS

Heart rate variability (HRV) is a noninvasive measure of autonomic input to heart rate that has been successfully used to estimate modulation of autonomic tone. The authors investigated to determine the normal ranges as a standardized tests of heart rate variability (HRV) for autonomic function tests in a large sample of healthy Koreans. The study also evaluated the effects of age, sex, and heart rate (HR) on the results of HRV and the values of HRV in hypertension, diabetes, and obesity group. Six hundred and thirty-seven healthy subjects who visited the health improvement center for medical examination were evaluated. A standardized 5-min resting study, including spectral analysis of HR, was used to all participants after an overnight fast. HRV (SA-2000E, Medicore, Korea) was spectrally determined by three components: total-frequency (TF) component (0.01 to 0.5 Hz), low-frequency (LF) component (0.04 to 0.15 Hz), and high-frequency (HF) component (0.15 to 0.5 Hz). Also two component ratio (LF/HF) was calculated. Routine laboratory and physical examinations were used to eliminate cardiovascular diseases and neurological disorders. The determinants of short-period HRV in a random sample of 366 men and 271 women from healthy subjects were assessed. The mean age of these subjects was 45.1 ± 10.7 years. The mean value of total power was 1106.9 ± 1109.1 ms²; SDNN was 35.9 ± 15.5 ms; rMSSD was 27.3 ± 15.6 ms for time domain analysis. The mean value of LF was 287.5 ± 384.1 ms²; HF was 227.0 ± 284.4 ms²; LF/HF was 2.2 ± 3.4 for frequency domain analysis. Additionally, men showed that their TP, LF, and LF/HF values were significantly higher than women whereas SDNN, rMSSD, HF showed no significant differences between sexes. With increasing age, there was no significant decrease in HR. TP, SDNN, LF, and HF were significantly decreased when getting older. On the contrary, LF/HF had no significant difference related to age. The study confirmed that SDNN and rMSSD were significantly lower in hypertension and diabetes group. In conclusion, middle-aged men had more pronounced sympathetic influence than women in cardiac regulation, and HRV declined linearly with age. In addition, HRV reflecting the function of autonomic nervous system was decreased in hypertension and diabetes group.     

Heart-rate variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the anticholinergic effects of clozapine and olanzapine?

Drug monitoring in psychiatry usually serves psychoactive drug plasma concentration measurement. Anticholinergic properties offer a faster approach to monitoring pharmacodynamic intraindividual effects of the drug by measuring their effects on heart rate variability (HRV), which is sympathetically and parasympathetically controlled via cholinergic synapses. The plasma concentrations of the atypical antipsychotics clozapine and olanzapine correlated with parameters of HRV in 59 patients suffering from schizophrenia or schizoaffective disorder. HRV during 4 minutes at rest was extracted from the ECG trace of a routine digital EEG registration in addition to blood sampling for plasma concentration measurement (HPLC method). We calculated sympathetically and parasympathetically controlled heart frequency bands (low, medium and high frequency) and other HRV parameters, coefficient of variation (CV), and root mean square of successive differences (RMSSD). All HRV parameters were significantly more impaired in clozapine patients (n = 33, mean clozapine plasma concentration 331 +/- 294 ng/ml) than in olanzapine patients (n = 26, mean olanzapine plasma concentration 42 +/- 32 ng/ml) and demonstrated 1.7 - 4.8 times the cardiac anticholinergic properties of clozapine in vivo. 14 out of 14 patients with a CV beyond 3.2 % had clozapine plasma concentrations below the proposed optimal therapeutic concentration of 350 ng/ml. All HRV parameters were inversely and significantly correlated with the clozapine plasma concentrations (such as lgCV: r = - 0.73, p < 0.001) and, to a lesser extent, with the olanzapine plasma concentrations (lgCV r = - 0.44, p < 0.05). These results underline the potential clinical value of HRV parameter extraction from routine ECGs in predicting plasma concentrations and objective individual neurocardiac effects of drugs with anticholinergic properties.     

Effects of combination psychotropic drug treatment on heart rate variability in psychiatric patients

The aim of this study was to evaluate the effects of combination psychotropic drug treatment on heart rate variability (HRV), which was mainly controlled by the parasympathetic nervous system. Mean R-R intervals (mRR) and coefficient of variation (CV), an index of HRV, were studied in 22 psychiatric patients and 21 age- and sex-matched healthy controls. Next, in the patient group focusing on both anticholinergic and antidopaminergic properties, combination psychotropic drug daily doses were converted into biperiden milligram equivalents (BPDeq) and chlorpromazine milligram equivalents (CPZeq), respectively. The relationship between mRR and CV and these equivalent dosages was examined. A significant reduction in both mRR (P < 0.05) and CV (P < 0.05) was found in the patient group. In addition, significant negative correlations were observed between the dose of BPDeq and mRR (P < 0.05), and between the dose of BPDeq and CV (P < 0.005). In contrast, no significant correlations were observed between the dose of CPZeq and either parameter. These findings suggest that the effects of combination psychotropic drug treatment on HRV are mainly due to their anticholinergic properties. Therefore, CV is a useful indicator to assess the parasympathetic activity of psychiatric patients under combination psychotropic drug treatment.     

Autonomic and emotion regulation in bereavement and depression

OBJECTIVES: Prior research suggests important differences between depression and the depressed feelings experienced in the context of bereavement, despite some overlap. Differences include an increase in restlessness, suggesting underlying physiological differences between the groups. METHOD: This study examined the level of depressive symptoms, heart rate (HR), and heart rate variability (HRV), and coping style of 10 bereaved, 10 depressed, and 10 control participants. RESULTS: Bereaved participants showed significantly higher HR than either depressed or control participants, while there were no such differences in HRV. Level of depression in the bereaved group correlated negatively with HRV. Additional analyses showed that the use of passive coping had a marginally significant negative correlation with HRV in bereaved subjects. CONCLUSION: The present data suggest that differences in HR and HRV could be associated with increased cardiovascular fatalities in bereaved individuals, known as the "broken heart phenomenon." These physiological differences have potential implications for both the mental and physical health of the bereaved.     

Determination of heart rate variability with an electronic stethoscope

Introduction

Heart rate variability (HRV) is widely used to characterize cardiac autonomic function by measuring beat-to-beat alterations in heart rate. Decreased HRV has been found predictive of worse cardiovascular (CV) outcomes. HRV is determined from time intervals between QRS complexes recorded by electrocardiography (ECG) for several minutes to 24 h. Although cardiac auscultation with a stethoscope is performed routinely on patients, the human ear cannot detect heart sound time intervals. The electronic stethoscope digitally processes heart sounds, from which cardiac time intervals can be obtained.

Methods

Accordingly, the objective of this study was to determine the feasibility of obtaining HRV from electronically recorded heart sounds. We prospectively studied 50 subjects with and without CV risk factors/disease and simultaneously recorded single lead ECG and heart sounds for 2 min.

Results

Time and frequency measures of HRV were calculated from R–R and S1–S1 intervals and were compared using intra-class correlation coefficients (ICC).

Conclusion

The majority of the indices were strongly correlated (ICC 0.73–1.0), while the remaining indices were moderately correlated (ICC 0.56–0.63). In conclusion, we found HRV measures determined from S1–S1 are in agreement with those determined by single lead ECG, and we demonstrate and discuss differences in the measures in detail. In addition to characterizing cardiac murmurs and time intervals, the electronic stethoscope holds promise as a convenient low-cost tool to determine HRV in the hospital and outpatient settings as a practical extension of the physical examination.     

EFFECTS OF QI-THERAPY (EXTERNAL QIGONG) ON CARDIAC AUTONOMIC TONE: A RANDOMIZED PLACEBO CONTROLLED STUDY

Heart-rate variability (HRV) was compared in 40 subjects receiving external Qi-therapy (QT) or placebo control therapy, in a randomized placebo controlled design experiment. There were significant time, and group × time interactions in heart rate (HR), low frequency (LF), high frequency (HF), and LF/HF. These suggest that QT reduced the HR and increased HRV as indicated by a reduced LF/HF power ratio of HRV. These findings suggest that QT stabilizes the sympathovagal function more than placebo therapy.     

Effects of Qi-therapy (external Qigong) on cardiac autonomic tone: a randomized placebo controlled study

Heart-rate variability (HRV) was compared in 40 subjects receiving external Qi-therapy (QT) or placebo control therapy, in a randomized placebo controlled design experiment. There were significant time, and group x time interactions in heart rate (HR), low frequency (LF), high frequency (HF), and LF/HF. These suggest that QT reduced the HR and increased HRV as indicated by a reduced LF/HF power ratio of HRV. These findings suggest that QT stabilizes the sympathovagal function more than placebo therapy.     

Behavioral inhibition system (BIS), behavioral activation system (BAS) and schizophrenia: relationship with psychopathology and physiology

OBJECTIVE: The Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) have been conceptualized as two neural motivational systems that regulate sensitivity to punishment (BIS) and reward (BAS). Imbalance in BIS and BAS levels has been reported to be related to various forms of psychopathology. Since sensitivity to stress has been supposed to be a pathway for the development of psychotic symptoms, the aim of this study is to examine BIS and BAS scores in schizophrenia and their relationship with psychopathology and physiology. METHOD: Forty-two patients with schizophrenia (26 men, 16 women), stable on atypical antipsychotics, and 37 healthy controls (17 men, 20 women) were assessed with the use of the Behavioral Inhibition and Behavioral Activation scales. Since increased average heart rate (HR) and decreased heart rate variability (HRV) have been reported in patients with schizophrenia and have been shown to correlate with inhibited behaviour, these psychophysiological measures were also obtained. The BIS/BAS data and HR/HRV data were both analyzed by a (M)ANOVA. Correlation coefficients were computed for associations between BIS/BAS data, HR/HRV data, and patient variables. RESULTS: On the BIS, patients showed higher sensitivity to threat than control subjects. Higher BIS sensitivity correlated with longer duration of illness, and lower negative symptoms on the PANSS. The BAS scores did not reveal differences between patients and controls. In patients, low BAS sensitivity correlated with low dosage of medication. On the physiological measures patients showed a significantly higher HR and lower HRV compared to controls, which was limited to clozapine treated patients. No correlations were found between HR/HRV scores and BIS/BAS scores or patient variables. CONCLUSIONS: Male as well as female patients with schizophrenia are more sensitive to threat than healthy controls. This may reflect a trait-related characteristic, and is not reflected in state-related psychophysiological measures.     

Acupuncture to Danzhong but not to Zhongting increases the cardiac vagal component of heart rate variability

There is currently no convincing evidence that acupuncture has any specific effects on autonomic nervous function as assessed by heart rate variability (HRV). We examined whether the stimulation of neighboring acupunctural points, Danzhong (CV17) and Zhongting (CV16) on the anterior median line of the thorax, induced different effects on HRV. In 14 healthy males, epifascial acupunctural stimulation (single instantaneous needle stimulation on the fascial surface without producing De-Qi sensation) was performed at CV17 and CV16 on different days in a clinical study utilizing a cross-over design. We found that the stimulation of CV17, but not of CV16, decreased the heart rate (P=0.01, repeated measures ANOVA) and increased the power of the high-frequency component of the HRV, an index of cardiac vagal activity (P=0.01). The low-frequency to high-frequency ratio, an index of sympathetic activity showed no significant changes for either point. Our observations could not be explained as either nonspecific or psychological/placebo effects of needle stimulation. This study provides strong evidence for the presence of a specific acupunctural point that causes the modulation of cardiac autonomic function.     

Sleep variability and cardiac autonomic modulation in adolescents – Penn State Child Cohort (PSCC) study

ObjectiveTo investigate the effects of objectively measured habitual sleep patterns on cardiac autonomic modulation (CAM) in a population-based sample of adolescents.MethodsWe used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. CAM was assessed by heart rate (HR) variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-h electrocardiogram, on a 30-min basis. The HRV indices included frequency domain (HF, LF, and LF/HF ratio), and time domain (SDNN, RMSSD, and heart rate or HR) variables. Actigraphy was used for seven consecutive nights to estimate nightly sleep duration and time in bed. The seven-night mean (SD) of sleep duration and sleep efficiency were used to represent sleep duration, duration variability, sleep efficiency, and efficiency variability, respectively. HF and LF were log-transformed for statistical analysis. Linear mixed-effect models were used to analyze the association between sleep patterns and CAM.ResultsAfter adjusting for major confounders, increased sleep duration variability and efficiency variability were significantly associated with lower HRV and higher HR during the 39-h, as well as separated by daytime and nighttime. For instance, a 1-h increase in sleep duration variability is associated with −0.14(0.04), −0.12(0.06), and −0.16(0.05) ms² decrease in total, daytime, and nighttime HF, respectively. No associations were found between sleep duration, or sleep efficiency and HRV.ConclusionHigher habitual sleep duration variability and efficiency variability are associated with lower HRV and higher HR, suggesting that an irregular sleep pattern has an adverse impact on CAM, even in healthy adolescents.     

Variability in emotional/behavioral problems in boys with oppositional defiant disorder or conduct disorder: the role of arousal

It is often reported that children with oppositional defiant disorder (ODD) or conduct disorder (CD) are under-aroused. However, the evidence is mixed, with some children with ODD/CD displaying high arousal. This has led to the hypothesis that different profiles of arousal dysfunction may exist within children with ODD/CD. This knowledge could explain variability within children with ODD/CD, both in terms of specific types of aggression as well as comorbid symptoms (e.g., other emotional/behavioral problems). We measured heart rate variability (HRV), heart rate (HR) and skin conductance level (SCL) during rest and stress, and obtained parent and teacher reports of aggression, anxiety, attention problems and autism traits in a sample of 66 ODD/CD and 36 non-clinical boys (aged 8–12 years). The ODD/CD group scored significantly higher on aggression, anxiety, attention problems and autism traits than the controls; boys with ODD/CD also had higher resting HRs than controls, but HR stress, HRV and SCL did not differ. Hierarchical regressions showed different physiological profiles in subgroups of boys with ODD/CD based on their type of aggression; a pattern of high baseline HR and SCL, but low stress HRV was related to reactive aggression, whereas the opposite physiological pattern (low HR, low stress SCL, high stress HRV) was related to proactive aggression. Furthermore, high stress SCL was related to anxiety symptoms, whereas low stress SCL was related to attention problems. These findings are important because they indicate heterogeneity within boys with ODD/CD and highlight the importance of using physiology to differentiate boys with different ODD/CD subtypes.     

Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans

PURPOSE: The purpose of this study was to determine if stimulation of the left vagus nerve (LVNS) with the neurocybernetic prosthesis (NCP) in humans is, as claimed in the literature, without cardiac chronotropic actions. METHODS: We analyzed 228 h of ECG recorded from five subjects with intractable epilepsy who had not benefited from LVNS, for effects on instantaneous heart rate (IHR) and heart rate variability (HRV). RESULTS: There were two main cardiac responses: (a) bradycardia, and (b) tachycardia during the first half, followed by bradycardia during the second half of stimulation (biphasic response). Multiphasic responses characterized by alternating bradycardia and tachycardia were rarely observed. HRV was either increased or decreased depending on the subject and on the stimulation parameters. HRV as a function of HR also showed high interindividual variability, and interestingly, in one case behaved paradoxically, increasing at higher and decreasing at lower heart rates. CONCLUSIONS: LVNS at high intensities has complex effects on IHR and HRV, which show large interindividual variability. These spectra of cardiac responses reflect the interplay of autonomic, visceral, and somatic sensory afferences and the role of central structures in their integration. These findings also point to the need for more comprehensive studies of cardiac function in humans implanted with the NCP, using sensitive methods for data processing and analysis such as those developed for this study.     

Autonomic reactivity to induced emotion as potential predictor of response to antidepressant treatment

Distinct factors have been identified as potential predictors of antidepressant treatment response. Although autonomic function changes have been described in depressive subjects, their value as predictors of antidepressant response has not been systematically evaluated. Eight un-medicated patients with major depressive order (MDD) have their skin conductance (SC) and heart rate variability (HRV) measured at basal condition and during four induced emotional states: happy, angry, sad and neutral. The high frequency (HF) and low frequency (LF) power parameters of HRV were assessed. Subsequently, patients were treated with fluoxetine 20 mg/day for 8 weeks. The antidepressant response was measured with the Beck Depression Inventory (BDI). The BDI percentage reduction correlated significantly with HRV responses during sad condition in LF power, and during happy condition with LF/HF ratio. The BDI percentage reduction also correlated significantly with HR responses in happy and in neutral conditions, and also with SC responses in neutral condition. These preliminary findings indicate that automatic responses to induced emotions may predict antidepressant response in MDD patients. Confirmatory studies are warranted.     

AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain

INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by ACE inhibitors has been demonstrated to reduce total mortality in cardiovascular diseases. This advantage was attributed in part to changes of autonomic cardiovascular control, exemplified by an increase of heart rate variability (HRV) and baroreflex gain (BRG). We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG. MATERIALS AND METHODS: In a double-blind randomized cross-over design 25 young males took eprosartan (600 mg/day) and placebo each for a period of 7 days with a wash-out period of at least 4 weeks in between. At the end of the intake phases simultaneous recordings of arterial blood pressure (AP; Finapres) and electrocardiogram (ECG) were taken. Power spectra of HRV and arterial blood pressure variability (APV) were calculated by fast Fourier transform (FFT) and served to calculate BRG. Ang-II levels were measured by radioimmunoassay. RESULTS: Eprosartan tended to lower mean AP, it slightly increased heart rate (HR) (p<0.05), and markedly increased circulating Ang-II levels (p<0.01). Eprosartan diminished the total power of HRV (p<0.05) and the BRG (p<0.01). The low/high frequency (LF/HF) ratio of HRV and the APV were not altered. CONCLUSIONS: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. We speculate that these findings are due to the marked increase in circulating angiotensin II (Ang II). Further studies are needed to clarify whether angiotensin type 1 (AT1) blockers with potential actions inside the blood-brain barrier (BBB) may have different effects on HRV and BRG.     

高血压合并急性脑血管病的心率变异分析

目的：探讨急性脑组织损害对原发性高血压（EH）患者心率变异（HRV）的影响。方法：对26例EH并急性脑血管病（ACVD）患者进行24h动态心电图HRV测定,并与20例EH元ACVD患者进行对比。结果:EH并ACVD组最小心率及平均心率明显高于无ACVD组（P＜0．01;P＜0．01）;24h相邻R-R间期之差的均方根（rMSSD)、相邻R-R间期之差大于50ms的心搏数占心搏总数的百分比（PNN50）较无ACVD组明显减低（P＜0．01;P＜0．001）。结论：EH合并ACVD患者HRV低于EH无ACVD患者,与其自主神经中枢损害有关。