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1.  Vagal Withdrawal and Sympathetic Overactivity Contribute to the Genesis of Early-Onset Pregnancy-Induced Hypertension 
Objective. In this study, we have assessed sympathovagal imbalance (SVI) by spectral analysis of heart rate variability (HRV) that contributes to the genesis of early-onset PIH. Methods. Body mass index (BMI), basal heart rate (BHR), blood pressure (BP) and HRV indices such as LFnu, HFnu, LF-HF ratio, mean RR, SDNN and RMSSD were assessed in normal pregnant women (Control group) and pregnant women having risk factors for PIH (Study group) at all the trimesters pregnancy. Retrospectively, those who did not develop PIH (Study group I) were separated from those who developed PIH (Study group II). Study group II was subdivided into early-onset and late-onset PIH. Sympathovagal balance (LF-HF ratio) was correlated with BMI, BHR and BP. Results. LF-HF ratio was significantly high in study group II compared to study group I and control group, and in early-onset PIH group compared to the late-onset category at all the trimesters of pregnancy, which was significantly correlated with BHR and BP. Alteration in HFnu in early-onset category was more prominent than the alteration in LFnu. Conclusion. Though the SVI in PIH is contributed by both sympathetic overactivity and vagal withdrawal, especially in early-onset type, SVI is mainly due to vagal inhibition.
doi:10.4061/2011/361417
PMCID: PMC3095942  PMID: 21629868
2.  Sympathovagal Imbalance in Prehypertensive Offspring of Two Parents versus One Parent Hypertensive 
Objective. Though prehypertension has strong familial predisposition, difference in pathophysiological mechanisms in its genesis in offspring of both parents and single parent hypertensive have not been elucidated. Methods. Body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), HR and BP response to standing, deep breathing difference, BP response to handgrip and spectral indices of heart rate variability (HRV) were analyzed in normotensive offspring of two parents hypertensive (Group I), normotensive offspring of one parent hypertensive (Group II), prehypertensive offspring of two parents hypertensive (Group III) and prehypertensive offspring of one parent hypertensive (Group IV). Results. Sympathovagal imbalance (SVI) in prehypertensive offspring was observed due to increased sympathetic and decreased vagal activity. In group III, SVI was more prominent with greater contribution by vagal withdrawal. LF-HF ratio, the marker of SVI was correlated more with diastolic pressure, 30 : 15 ratio and E : I ratio in prehypertensives and the degree of correlation was more in group III prehypertensives. Conclusion. Vagal withdrawal plays a critical role in development of SVI in prehypertensive offspring of hypertensive parents. The intensity of SVI was more in offspring of two parents hypertensive compared to single parent hypertensive.
doi:10.4061/2011/263170
PMCID: PMC3202093  PMID: 22121472
3.  Painful Diabetic Neuropathy Is Associated With Greater Autonomic Dysfunction Than Painless Diabetic Neuropathy 
Diabetes Care  2010;33(7):1585-1590.
OBJECTIVE
Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN.
RESEARCH DESIGN AND METHODS
Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed.
RESULTS
HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 ± 1.08 [means ± SD] vs. 2.67 ± 1.56), TP (5.73 ± 1.28 vs. 4.79 ± 1.51), and SDNN (2.91 ± 0.65 vs. 1.62 ± 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT.
CONCLUSIONS
This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN.
doi:10.2337/dc09-2314
PMCID: PMC2890363  PMID: 20587724
4.  Autonomous Nervous System Activity in Women with Detrusor Overactivity 
Korean Journal of Urology  2010;51(3):183-186.
Purpose
To identify autonomic dysfunction among patients with urinary incontinence (UI) with or without detrusor overactivity (DO), we measured and compared heart rate variability (HRV) in these groups.
Materials and Methods
We studied HRV in 12 female UI patients with DO (mean age, 57.3±11.0 years) and 53 female UI patients without DO (mean age, 56.8±9.8 years). HRV parameters were measured by SA-3000P®. Heart rates, the time domain index, and the frequency domain index were compared. To compare time domain indexes, we used the standard deviation of the N-N interval (SDNN), the square root of the mean squared differences of successive N-N intervals (RMSSD), and the frequency domain indexes total power (TP), very low frequency (VLF), low frequency (LF), high frequency (HF), and the low-frequency/high-frequency ratio (LF/HF ratio).
Results
RMSSD values were lower in UI patients with DO than in those without DO, but the values of SDNN and HR showed no significant difference. Whereas the values of LF and HF were lower in UI patients with DO than in those without DO, the LF/HF ratio was higher. TP and VLF were not significantly different.
Conclusions
RMSSD, HF, and LF were lower in DO patients than in controls without DO, but the LF/HF ratio was higher. This suggests that both sympathetic and parasympathetic activity is attenuated in DO, but the autonomic imbalance is higher.
doi:10.4111/kju.2010.51.3.183
PMCID: PMC2855458  PMID: 20414394
Heart rate; Urinary incontinence
5.  The Relationship between Heart Rate Variability and Adiposity Differs for Central and Overall Adiposity 
Journal of Obesity  2012;2012:149516.
While frank obesity is associated with reduced HRV, indicative of poorer autonomic nervous system (ANS) function, the association between body mass index (BMI) and HRV is less clear. We hypothesized that effects of adiposity on ANS are mostly mediated by visceral fat and less by subcutaneous fat; therefore, centrally distributed adipose tissue, that is, waist circumference (WC), should be more strongly associated with HRV than overall adiposity (BMI). To examine this hypothesis, we used data collected in a subset of the Baltimore Longitudinal Study of Aging to compare strength of association between HRV and WC to that of HRV and BMI. Time domain HRV variables SDNN (standard deviation of successive differences in normal-to-normal (N-N) intervals) and RMSSD (root mean square of successive differences in N-N intervals) were calculated from 24-hour Holter recordings in 159 participants (29–96 years). Increasing WC was associated with decreasing SDNN and RMSSD in younger but not older participants (P value for WC-by-age interaction = 0.003). BMI was not associated with either SDNN or RMSSD at any age. In conclusion, central adiposity may contribute to sympathetic and parasympathetic ANS declines early in life.
doi:10.1155/2012/149516
PMCID: PMC3357556  PMID: 22649714
6.  Transcutaneous Electrical Stimulation of Acupoints Changes Body Composition and Heart Rate Variability in Postmenopausal Women with Obesity 
This study aimed to evaluate the effect of transcutaneous electric acupoint stimulations (TEAS) on body composition and heart rate variability (HRV) in postmenopausal women with obesity. In this prospective study, 49 postmenopausal women were recruited in Taiwan. Body composition was used as a screening test for obesity (percentage body fat > 30%, waist circumference > 80 cm). The experimental group (n = 24) received TEAS treatment 30 min twice per week for 12 weeks at the Zusanli (ST 36) and Sanyinjiao (SP 6) acupoints. The control group (n = 25) did not receive any intervention. The study of HRV was analyzed by time (standard deviation of the normal-to-normal (NN) intervals (SDNN) and square root of the mean squared differences of successive NN intervals (RMSSD) indices) and frequency domain methods. Power spectral components were obtained at low (LF) and high (HF) frequencies. Body composition and HRV values were measured at the 4th, 8th, and 12th weeks. A total of 40 subjects completed this study. Waist circumference and percentage body fat in the experimental group (n = 20) were significantly less than those of the control group (n = 20) at the 8th and 12th weeks (all P < .05). Additionally, at the same time points, percentage lean body mass in the experimental group was significantly greater than that in the control group (P < .05). SDNN values increased significantly at the 4th and 8th weeks when compared with the control group (all P < .05). At 12 weeks, SDNN value was not significantly different from that of the control group (P = .105). TEAS treatment improves body composition, and has a transient effect on the HRV in postmenopausal women with obesity.
doi:10.1093/ecam/nep145
PMCID: PMC3137740  PMID: 19773390
7.  Night Heart Rate Variability and Particulate Exposures among Boilermaker Construction Workers 
Environmental Health Perspectives  2007;115(7):1046-1051.
Background
Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear.
Objective
Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures.
Methods
We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730–2130 hours), and night (0000–0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors.
Results
Mean (± SD) PM2.5 exposure was 0.73 ± 0.50 mg/m3 and ranged from 0.04 to 2.70 mg/m3. We observed a consistent inverse exposure–response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m3 increase in PM2.5 was associated with a change of −8.32 [95% confidence interval (CI), −16.29 to −0.35] msec nighttime rMSSD, −14.77 (95% CI, −31.52 to 1.97) msec nighttime SDNN, and −8.37 (95% CI, −17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking.
Conclusion
Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV.
doi:10.1289/ehp.10019
PMCID: PMC1913585  PMID: 17637921
environmental cardiology; heart rate variability; occupational; particulate exposures; welders
8.  The circadian pattern of cardiac autonomic modulation in a middle-aged population 
Clinical Autonomic Research  2011;21(3):143-150.
Objectives
To examine the circadian pattern of cardiac autonomic modulation (CAM) and its attributes in general population.
Methods
We obtained 24-h beat-to-beat RR data using a high resolution 12-lead Holter ECG in a community-dwelling sample of 115 non-smokers. We performed heart rate variability (HRV) analysis on the normal RRs from each 5-min segment to obtain time-specific HRV indices: high (HF; 0.15–0.40 Hz) and low (LF; 0.04–0.15 Hz) frequency powers, standard deviation of RR intervals (SDNN), and the square root of the mean of the sum of the squared differences of the adjacent RR intervals (RMSSD). For each individual, we fit the segment-specific HRV data to a cosine periodic function, and estimated 3 individual-level cosine function parameters to quantify the circadian variation: the mean (M), amplitude (A), and acrophase (θ). We then used a random-effects meta-analysis to summarize the M, A, and θ, and their 95% confidence intervals (CI).
Results
The mean age was 56 (SD 8) years, with 63% female and 76% white. The averages of M, A and θ (95%CI) of log HF were 3.59 (3.43–3.76) ms2, 0.61 (0.54–0.68) ms2, and 3:10 (2:25–3:55) AM, respectively, and that of RMSSD were 22.3 (20.5–24.1) ms, 6.5 (5.4–7.5) ms, 3:45 (2:55–4:35) AM, respectively. Older age is associated with lower mean of HRV. Males have higher oscillation amplitude than females. The acrophase of LF/HF was earlier in females than in males, and in younger individuals than in older individuals.
Conclusions
The circadian pattern of CAM can be quantified by 3 cosine parameters of HRV, which are correlated with age and gender.
doi:10.1007/s10286-010-0112-4
PMCID: PMC3093547  PMID: 21240538
Autonomic modulation; Heart rate variability; Periodic rhythm; Community population
9.  Differential Association of Adiposity Measures with Heart Rate Variability Measures in Koreans 
Yonsei Medical Journal  2012;54(1):55-61.
Purpose
Although obesity has been associated with imbalances in cardiac autonomic nervous system, it is unclear whether there are differential relationships between adiposity measures and heart rate variability (HRV) measures. We aimed to examine differences in the relationship between adiposity measures and HRV indices in a healthy Korean population.
Materials and Methods
In all, 1409 non-smokers (811 males, 598 females) without known histories of cardiovascular (CV), endocrine, or neurological diseases underwent adiposity measurements [(body mass index (BMI), percentage of body fat mass (PBF), and waist-to-hip ratio (WHR)], the HRV assessment (SDNN, RMSSD, LF, HF, LF/HF, and pNN50), and examination for CV risk factors (fasting glucose, LDL-cholesterol, HDL-cholesterol, triglycerides, hs-CRP, and blood pressure).
Results
Compared with BMI and PBF, WHR was more strongly correlated with each HRV index and more likely to predict decreased HRV (<15 percentile vs. ≥15 percentile of each HRV index) in ROC curves analysis. In linear regression analysis, all adiposity measures were inversely associated with each HRV measure before adjusting for age, gender, and CV risk factors (p<0.05). After adjusting for the covariates, WHR was inversely related to RMSSD, LF, and pNN50; PBF with RMSSD, HF, and pNN50; BMI with RMSSD (p<0.05). The inversed association between HRV indices and the gender-specific WHR tertile was significant for subjects with BMI ≥25 kg/m2, but not for those with BMI <25 kg/m2.
Conclusion
WHR and PBF appear to be better indicators for low HRV than BMI, and the association between abdominal adiposity and HRV may be stronger in overweight subjects.
doi:10.3349/ymj.2013.54.1.55
PMCID: PMC3521274  PMID: 23225799
Heart rate variability; adiposity; abdominal fat; cardiac autonomic function; obesity
10.  A pilot study on short term heart rate variability & its correlation with disease activity in Indian patients with rheumatoid arthritis 
Background & objectives:
Cardiovascular complications may lead to mortality in patients with rheumatoid arthritis (RA). We assessed heart rate variability (HRV), an important autonomic function, to quantify the risk for cardiovascular complications in Indian patients with RA.
Methods:
The study was carried out in RA patients (n=45) diagnosed as per American College of Rheumatology criteria and healthy controls. HRV recording and analysis was done using Nevrokard software using time and frequency domain analyses. The overall autonomic tone, parasympathetic drive, sympathetic drive and sympatho-vagal ratio were quantified by using various parameters. It included standard deviation of all R-R intervals (SDNN), standard deviation of successive differences between adjoining normal cycles (SDSD), root-mean square of successive differences (RMSSD), and number of R-R intervals differing by >50 ms from adjacent intervals (NN50) in the time domain analysis. In frequency domain analysis, low frequency (LF) and high frequency (HF), LF/HF and total power were assessed.
Results:
Demographic profile was comparable between groups; however, systolic BP was higher in patients with RA. SDNN, SDSD, RMSSD, NN50, LF and HF power and total power (ms × ms) were significantly lower in patients with RA versus healthy controls (P<0.001). Disease activity score at 28 joints indicating severity of the disease was significantly and positively correlated with SDSD (r=0.375, R2=14.06; P=0.045) while LF and HF power (ms × ms) were significantly and inversely correlated with rheumatoid factor (r=-0.438 and -0.445; R2=19.1 and 19.8; P=0.017 and 0.016, respectively).
Interpretation & conclusions:
HRV was significantly altered in patients with RA and independently associated with disease activity. Hence autonomic function testing, using HRV, may be useful as part of cardiovascular risk assessment in these patients.
PMCID: PMC3516026  PMID: 23168699
Cardiovascular status; rheumatoid arthritis; short term heart rate variability
11.  Lack of Association of Estrogen Receptor Alpha Gene Polymorphisms with Cardiorespiratory and Metabolic Variables in Young Women 
This study examined the association of estrogen receptor alpha gene (ESR1) polymorphisms with cardiorespiratory and metabolic parameters in young women. In total, 354 healthy women were selected for cardiopulmonary exercise testing and short-term heart rate (HR) variability (HRV) evaluation. The HRV analysis was determined by the temporal indices rMSSD (square root of the mean squared differences of successive R–R intervals (RRi) divided by the number of RRi minus one), SDNN (root mean square of differences from mean RRi, divided by the number of RRi) and power spectrum components by low frequency (LF), high frequency (HF) and LF/HF ratio. Blood samples were obtained for serum lipids, estradiol and DNA extraction. ESR1 rs2234693 and rs9340799 polymorphisms were analyzed by PCR and fragment restriction analysis. HR and oxygen uptake (VO2) values did not differ between the ESR1 polymorphisms with respect to autonomic modulation. We not find a relationship between ESR1 T–A, T–G, C–A and C–G haplotypes and cardiorespiratory and metabolic variables. Multiple linear regression analysis demonstrated that VO2, total cholesterol and triglycerides influence HRV (p < 0.05). The results suggest that ESR1 variants have no effect on cardiorespiratory and metabolic variables, while HRV indices are influenced by aerobic capacity and lipids in healthy women.
doi:10.3390/ijms131013691
PMCID: PMC3497348  PMID: 23202974
estrogen receptor-α gene polymorphisms; heart rate variability; aerobic capacity; lipids
12.  High N-Terminal Pro-B-Type Natriuretic Peptide Levels Are Associated with Reduced Heart Rate Variability in Acute Myocardial Infarction 
PLoS ONE  2012;7(10):e44677.
Aim
We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV) and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP) in patients with acute myocardial infarction (MI).
Methods and Results
The mean of standard deviation of RR intervals (SDNN), the percentage of RR intervals with >50 ms variation (pNN50), square root of mean squared differences of successive RR intervals (rMSSD), and frequency domain parameters (total power (TP), high frequency and low frequency power ratio (LF/HF)) were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche) was measured from blood samples taken on admission. The median (IQR) Nt-proBNP level was 681(159–2432) pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = −0.19, p<0.001), LF/HF (r = −0.37, p<0.001), and LF (r = −0.29, p<0.001) but not HF (r = −0.043, p = 0.172). Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE) = −0.065(0.015), p<0.001)), even after adjustment for confounders.
Conclusions
In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI.
doi:10.1371/journal.pone.0044677
PMCID: PMC3470551  PMID: 23071500
13.  Association of Heart Rate Variability with the Framingham Risk Score in Healthy Adults 
Korean Journal of Family Medicine  2011;32(6):334-340.
Background
The aim of this study was to investigate the relationship between heart rate variability (HRV), the Framingham risk score (FRS), and the 10-year risk of coronary heart disease (CHD) development among Korean adults.
Methods
The subjects were 85 healthy Korean adults recruited from a health check-up center. The FRS and 10-year risk of CHD development were calculated.
Results
The FRS in men was inversely correlated with the standard deviation of all normal to normal RR-intervals (SDNN); the root mean square successive difference (RMSSD); the percentage of successive normal cardiac inter-beat intervals greater than 20 ms, 30 ms, and 50 ms (pNN20, pNN30, pNN50); the low frequency (LF); and the high frequency (HF) (P < 0.05). There was no significant relationship between the FRS and HRV in women. Overall, in the receiver operating characteristic (ROC) analysis, the RMSSD, HF, SDNN, LF, LF/HF ratio, and pNN30 predicted an increased 10-year CHD risk. After adjusting for sex and body mass index, those with greater than one standard deviation in the RMSSD, HF, and LF had a 52-59% reduction in their 10-year risk of CHD development ≥ 10%.
Conclusion
This study therefore indicates that the HRV indices, particularly SDNN, RMSSD, pNN30, LF, and HF may be useful parameters for the assessment of CHD risk. Most notably, the usefulness of these HRV measures as indicators for CHD risk evaluation may be greater among men than among women.
doi:10.4082/kjfm.2011.32.6.334
PMCID: PMC3383143  PMID: 22745871
Heart Rate; Risk Assessment; Electrocardiography
14.  Effects of Particle Size Fractions on Reducing Heart Rate Variability in Cardiac and Hypertensive Patients 
Environmental Health Perspectives  2005;113(12):1693-1697.
It is still unknown whether the associations between particulate matter (PM) and heart rate variability (HRV) differ by particle sizes with aerodynamic diameters between 0.3 μm and 1.0 μm (PM0.3–1.0), between 1.0 μm and 2.5 μm (PM1.0–2.5), and between 2.5 μm and 10 μm (PM2.5–10). We measured electrocardiographics and PM exposures in 10 patients with coronary heart disease and 16 patients with either prehypertension or hypertension. The outcome variables were standard deviation of all normal-to-normal (NN) intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), low frequency (LF; 0.04–0.15 Hz), high frequency (HF; 0.15–0.40 Hz), and LF:HF ratio for HRV. The pollution variables were mass concentrations of PM0.3–1.0, PM1.0–2.5, and PM2.5–10. We used linear mixed-effects models to examine the association between PM exposures and log10-transformed HRV indices, adjusting for key personal and environmental attributes. We found that PM0.3–1.0 exposures at 1- to 4-hr moving averages were associated with SDNN and r-MSSD in both cardiac and hypertensive patients. For an interquartile increase in PM0.3–1.0, there were 1.49–4.88% decreases in SDNN and 2.73–8.25% decreases in r-MSSD. PM0.3–1.0 exposures were also associated with decreases in LF and HF for hypertensive patients at 1- to 3-hr moving averages except for cardiac patients at moving averages of 2 or 3 hr. By contrast, we found that HRV was not associated with either PM1.0–2.5 or PM2.5–10. HRV reduction in susceptible population was associated with PM0.3–1.0 but was not associated with either PM1.0–2.5 or PM2.5–10.
doi:10.1289/ehp.8145
PMCID: PMC1314907  PMID: 16330349
air pollution; autonomic system; epidemiology; heart rate variability; particulate matter
15.  Sensitivity, specificity and predictive values of linear and nonlinear indices of heart rate variability in stable angina patients 
Background
Decreased heart rate variability (HRV) is related to higher morbidity and mortality. In this study we evaluated the linear and nonlinear indices of the HRV in stable angina patients submitted to coronary angiography.
Methods
We studied 77 unselected patients for elective coronary angiography, which were divided into two groups: coronary artery disease (CAD) and non-CAD groups. For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 40 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal], NN50 [total number of adjacent RR intervals with a difference of duration greater than 50ms] and RMSSD [root-mean square of differences]) and frequency domains ultra-low frequency (ULF) ≤ 0,003 Hz, very low frequency (VLF) 0,003 – 0,04 Hz, low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.40 Hz) as well as the ratio between LF and HF components (LF/HF). In relation to the nonlinear indices we evaluated SD1, SD2, SD1/SD2, approximate entropy (−ApEn), α1, α2, Lyapunov Exponent, Hurst Exponent, autocorrelation and dimension correlation. The definition of the cutoff point of the variables for predictive tests was obtained by the Receiver Operating Characteristic curve (ROC). The area under the ROC curve was calculated by the extended trapezoidal rule, assuming as relevant areas under the curve ≥ 0.650.
Results
Coronary arterial disease patients presented reduced values of SDNN, RMSSD, NN50, HF, SD1, SD2 and -ApEn. HF ≤ 66 ms2, RMSSD ≤ 23.9 ms, ApEn ≤−0.296 and NN50 ≤ 16 presented the best discriminatory power for the presence of significant coronary obstruction.
Conclusion
We suggest the use of Heart Rate Variability Analysis in linear and nonlinear domains, for prognostic purposes in patients with stable angina pectoris, in view of their overall impairment.
doi:10.1186/1755-7682-5-31
PMCID: PMC3549885  PMID: 23110977
Heart rate variability; Nonlinear dynamics; Coronary artery disease; Cardiovascular physiology; Stable angina
16.  Acute Application of Bilevel Positive Airway Pressure Influences the Cardiac Autonomic Nervous System 
Clinics (Sao Paulo, Brazil)  2009;64(11):1085-1092.
INTRODUCTION
Noninvasive positive pressure has been used to treat several diseases. However, the physiological response of the cardiac autonomic system during bilevel positive airway pressure (Bilevel) remains unclear.
OBJECTIVE
The aim of this study was to evaluate the heart rate variability (HRV) during Bilevel in young healthy subjects.
METHODS
Twenty men underwent 10-minute R-R interval recordings during sham ventilation (SV), Bilevel of 8–15 cmH2O and Bilevel of 13–20 cmH2O. The HRV was analyzed by means of the parallel R-R interval (mean R-Ri), the standard deviation of all R-Ri (SDNN), the root mean square of the squares of the differences between successive R-Ri (rMSSD), the number of successive R-Ri pairs that differ by more than 50 milliseconds (NN50), the percentage of successive R-Ri that differ by more than 50 milliseconds (pNN50), the low frequency (LF), the high frequency (HF) and SD1 and SD2. Additionally, physiological variables, including blood pressure, breathing frequency and end tidal CO2, were collected. Repeated-measures ANOVA and Pearson correlation were used to assess the differences between the three studied conditions and the relationships between the delta of Bilevel at 13–20 cmH2O and sham ventilation of the HRV indexes and the physiological variables, respectively.
RESULTS
The R-Ri mean, rMSSD, NN50, pNN50 and SD1 were reduced during Bilevel of 13–20 cmH2O as compared to SV. An R-Ri mean reduction was also observed in Bilevel of 13–20 cmH2O compared to 8–15 cmH2O. Both the R-Ri mean and HF were reduced during Bilevel of 8–15 cmH2O as compared to SV, while the LF increased during application of Bilevel of 8–15 cmH2O as compared to SV. The delta (between Bilevel at 13–20 cmH2O and sham ventilation) of ETCO2 correlated positively with LF, HF, the LF/HF ratio, SDNN, rMSSD and SD1. Acute application of Bilevel was able to alter the cardiac autonomic nervous system, resulting in a reduction in parasympathetic activity and an increase in sympathetic activity and higher level of positive pressure can cause a greater influence on the cardiovascular and respiratory system.
doi:10.1590/S1807-59322009001100008
PMCID: PMC2780525  PMID: 19936182
Heart rate; Neural control; Heart rate variability; Noninvasive positive pressure ventilation; Physiological responses
17.  A longitudinal study in youth of heart rate variability at rest and in response to stress 
Background
Few longitudinal studies have examined ethnic and sex differences, predictors and tracking stabilities of heart rate variability (HRV) at rest and in response to stress in youths and young adults.
Methods
Two evaluations were performed approximately 1.5 years apart on 399 youths and young adults (189 European Americans [EAs] and 210 African Americans [AAs]; 190 males and 209 females). HRV was measured at rest and during a video game challenge.
Results
AAs showed significantly higher resting root mean square of successive differences (RMSSD) of normal R-R intervals and high-frequency (HF) power than EAs (Ps< 0.01). Females displayed larger decrease of RMSSD and HF during video game challenge than males (Ps< 0.05). These ethnic and sex differences were consistent across 1.5 years. No significant sex difference of resting HRV or ethnic difference of HRV response to stress was observed. In addition to age, ethnicity or sex, baseline resting HRV or HRV response to stress are predictors of the corresponding variables 1.5 years later (Ps< 0.01). Furthermore, weight gain indexed by either body mass index or waist circumference predicts declined resting HRV levels during follow up (Ps < 0.05). Tracking stabilities were high (>0.5) for resting HRV, but relatively low (<0.3) for HRV in response to stress.
Conclusion
AAs show higher resting HRV than EAs, and females display greater HRV response to stress than males; and these ethnic and sex differences are consistent across 1.5 years. Resting HRV declines with weight gain.
doi:10.1016/j.ijpsycho.2009.03.002
PMCID: PMC2719684  PMID: 19285108
heart rate variability; longitudinal study; sex; ethnicity
18.  The Effect of Lavender Aromatherapy on Autonomic Nervous System in Midlife Women with Insomnia 
The objective of this study is to determine the effects of 12 weeks of lavender aromatherapy on self-reported sleep and heart rate variability (HRV) in the midlife women with insomnia. Sixty-seven women aged 45–55 years, with a CPSQI (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were recruited from communities in Taiwan. The experimental group (n = 34) received lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total of 24 times. The control group (n = 33) received health education program for sleep hygiene with no intervention. The study of HRV was analyzed by time- and frequency-domain methods. Significant decrease in mean heart rate (HR) and increases in SDNN (standard deviation of the normal-to-normal (NN) intervals), RMSDD (square root of the mean squared differences of successive NN intervals), and HF (high frequency) of spectral powers analysis after lavender inhalation were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of study subjects was significantly decreased in the experimental group (P < 0.001), while no significant difference was observed across the same time period (P = 0.776) in the control group. Resting HR and HRV measurements at baseline 1 month and 3 months after allocation showed no significant difference between the experimental and control groups. The study demonstrated that lavender inhalation may have a persistent short-term effect on HRV with an increase in parasympathetic modulation. Women receiving aromatherapy experienced a significant improvement in sleep quality after intervention. However, lavender aromatherapy does not appear to confer benefit on HRV in the long-term followup.
doi:10.1155/2012/740813
PMCID: PMC3159017  PMID: 21869900
19.  Dysfunction of Autonomic Nervous System in Childhood Obesity: A Cross-Sectional Study 
PLoS ONE  2013;8(1):e54546.
Objective
To assess the distribution of autonomic nervous system (ANS) dysfunction in overweight and obese children.
Methods
Parasympathetic and sympathetic ANS function was assessed in children and adolescents with no evidence of impaired glucose metabolism by analysis of heart rate variability (low frequency power ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio, ratio of longest RR interval during expiration to shortest interval during inspiration (E/I ratio), root mean square of successive differences (RMSSD); sympathetic skin response (SSR); and quantitative pupillography (pupil diameter in darkness, light reflex amplitude, latency, constriction velocity, re-dilation velocity). The relationship of each ANS variable to the standard deviation score of body mass index (BMI-SDS) was assessed in a linear model considering age, gender and pubertal stage as co-variates and employing an F-statistic to compare the fit of nested models. Group comparisons between normal weight and obese children as well as an analysis of dependence on insulin resistance (as indexed by the Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) were performed for parameters shown to correlate with BMI-SDS. Statistical significance was set at 5%.
Results
Measurements were performed in 149 individuals (mean age 12.0 y; 90 obese 45 boys; 59 normal weight, 34 boys). E/I ratio (p = 0.003), ln(HF) (p = 0.03), pupil diameter in darkness (p = 0.01) were negatively correlated with BMI-SDS, whereas ln(LF/HF) was positively correlated (p = 0.05). Early re-dilation velocity was in trend negatively correlated to BMI-SDS (p = 0.08). None of the parameters that depended significantly on BMI-SDS was found to be significantly correlated with HOMA-IR.
Conclusion
These findings demonstrate extended ANS dysfunction in obese children and adolescents, affecting several organ systems. Both parasympathetic activity and sympathetic activity are reduced. The conspicuous pattern of ANS dysfunction raises the possibility that obesity may give rise to dysfunction of the peripheral autonomic nerves resembling that observed in normal-weight diabetic children and adolescents.
doi:10.1371/journal.pone.0054546
PMCID: PMC3554723  PMID: 23358101
20.  Increased Sympathetic Nervous System Activity 
Texas Heart Institute Journal  2003;30(2):100-104.
In this prospective study, we set out to determine whether analysis of heart rate variability (HRV) in patients with exercise-induced ventricular tachycardia (EIVT) and normal coronary arteries would reveal increased sympathetic nervous system activity. From January 1996 to December 2001, we compared 16 patients with EIVT and normal coronary arteries with an age- and sex-matched control group. Analysis of HRV showed that parameters indicative of parasympathetic activity were lower in our study group than in our control group: standard deviation of the mean of qualified NN intervals (SDNN), 81.6 ± 14.5 vs 139.3 ± 11.0, P < 0.001; root mean square of successive differences (RMSSD), 22.3 ± 4.8 vs 36.3 ± 6.6, P < 0.001; number of NN intervals that differed by more than 5 ms from the adjacent interval, divided by the total number of NN intervals (PNN50), 4.8 ± 1.5 vs 10.2 ± 3.1, P < 0.001; and high-frequency component (HF), 28.7 ± 2.5 vs 32.4 ± 3.9, P < 0.05. Conversely, parameters indicative of sympathetic activity were higher in patients with EIVT: low-frequency component (LF), 71.2 ± 5.0 vs 52.0 ± 5.8, P < 0.001; and absolute low/high frequency component ratio (LF/HF), 2.7 ± 0.2 vs 1.6 ± 0.2, P < 0.001. There was a positive correlation between EIVT and LF (r = 0.79, P < 0.001) and between EIVT and LF/HF (r = 0.81, P < 0.001). Our results suggest the presence of increased sympathetic and decreased parasympathetic tone in patients with EIVT. We conclude that EIVT is associated with an imbalance in the autonomic nervous system. (Tex Heart Inst J 2003;30:100–4)
PMCID: PMC161893  PMID: 12809249
Electrocardiography; exercise test/adverse effects; heart rate; parasympathetic nervous system; sympathetic nervous system; tachycardia, paroxysmal/etiology; tachycardia, ventricular/etiology; ventricular premature complexes/etiology
21.  The influence of oral water load on energy expenditure and sympatho-vagal balance in obese and normal weight women 
Archives of Medical Science : AMS  2012;8(6):1003-1008.
Introduction
Oral water load may increase the energy expenditure (EE) by stimulation of sympathetic dependent thermogenesis. Thus, drinking of water may be helpful in weight reduction. The aim of the study is to assess the influence of water load on energy expenditure and sympathetic activity in obese and normal weight women.
Material and methods
Forty-five women were included. Energy expenditure was measured twice, in the morning and after oral water load, by the indirect calorimetric method. The heart rate variability parameters low frequency (LF), high frequency (HF), LF/HF index, standard deviation of normal RR intervals (SDNN) and root mean square difference among successive RR normal intervals (rMSSD) were used for the indirect assessment of the sympatho-vagal balance.
Results
Resting energy expenditure (REE) was significantly higher in obese than in normal weight women (1529 ±396 kcal/day vs. 1198 ±373 kcal/day; p = 0.02). In both study groups after water load EE increased significantly (by 20% and by 12%, corresponding to 8.6 kcal/h and 5.2 kcal/h respectively), while, LF/HF index increased simultaneously. The increase of energy expenditure (EE) did not exceed the energetic cost of water heating, from room to body temperature – 15 kcal/1000 ml. There was no correlation between changes of energy expenditure (EE) and heart rate variability (HRV) parameters.
Conclusions
The increase of EE induced by water load is mostly related to the heating of the consumed water to body temperature. The assessment of autonomic balance by means of standard HRV indices had been found insufficient for detection of actually operating mechanisms.
doi:10.5114/aoms.2012.32406
PMCID: PMC3542490  PMID: 23319974
energy expenditure; sympatho-vagal balance; oral water load; obesity
22.  Determinants for Heart Rate Variability in a Normal Korean Population 
Journal of Korean Medical Science  2011;26(10):1293-1298.
This study examined the normal ranges and the determinants for various parameters of the short-term heart rate variability (HRV) measurements in a large Korean sample of healthy people. HRV measurements were obtained in 2,748 healthy men and 735 healthy women 18-65 yr of age. The mean total power (TP), low frequency (LF), high frequency (HF), and LF/HF ratio were 1,358.9 ± 1,840.8 ms2, 417.3 ± 807.6 ms2, 254.1 ± 414.1 ms2, and 2.4 ± 20.9 ms2 in the frequency-domain spectral analysis. The mean standard deviation of the normal-to-normal (NN) interval (SDNN) and the square root of the mean squared differences of successive NN intervals (RMSSD) were 39.6 ± 22.1 ms and 29.7 ± 18.1 ms in the time-domain analysis. The female subjects had significantly higher SDNN, RMSSD, and HF values than the male subjects. After controlling for age, there was no statistically significant difference in the SDNN. Quantile regression analysis showed that age and mean heart rate had a significant impact on short-term HRV measurement. Given that both clinicians and researchers are increasingly relying on short-term HRV assessment in measuring stress, our work suggests that age and gender should be considered as independent determinants for HRV.
doi:10.3346/jkms.2011.26.10.1293
PMCID: PMC3192339  PMID: 22022180
Age; Gender; Heart Rate Variability; Autonomic Nervous System; Psychophysiology
23.  Fractal correlation property of heart rate variability in chronic obstructive pulmonary disease 
Background
It was reported that autonomic nervous system function is altered in subjects with chronic obstructive pulmonary disease (COPD). We evaluated short- and long-term fractal exponents of heart rate variability (HRV) in COPD subjects.
Patients and methods
We analyzed data from 30 volunteers, who were divided into two groups according to spirometric values: COPD (n = 15) and control (n = 15). For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 30 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal] and RMSSD [root-mean square of differences]) and frequency domains (low frequency [LF], high frequency [HF], and LF/HF), and the short- and long-term fractal exponents were obtained by detrended fluctuation analysis. We considered P < 0.05 to be a significant difference.
Results
COPD patients presented reduced levels of all linear exponents and decreased short-term fractal exponent (alpha-1: 0.899 ± 0.18 versus 1.025 ± 0.09, P = 0.026). There was no significant difference between COPD and control groups in alpha-2 and alpha-1/alpha-2 ratio.
Conclusion
COPD subjects present reduced short-term fractal correlation properties of HRV, which indicates that this index can be used for risk stratification, assessment of systemic disease manifestations, and therapeutic procedures to monitor those patients.
doi:10.2147/COPD.S15099
PMCID: PMC3034287  PMID: 21311690
pulmonary disease; chronic obstructive; heart rate; nervous system; cardiology
24.  Heart rate variability and biomarkers of systemic inflammation in patients with stable coronary heart disease: findings from the Heart and Soul Study 
Background
Chronic low-grade systemic inflammation is a key component in atherogenesis. Decreased heart rate variability (HRV), a strong predictor of cardiovascular events, has been associated with elevations in circulating levels of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen in apparently healthy individuals. We investigated whether decreased HRV is associated with inflammatory markers in patients with coronary heart disease (CHD).
Methods
We studied the relationship between HRV and CRP, IL-6, and fibrinogen in 862 outpatients with CHD. All participants provided fasting blood samples and underwent 24-h ambulatory monitoring to assess time-domain measures of HRV (MeanNN, SDNN, SDANN, and RMSSD). Regression analyses were adjusted for age, sex, ethnicity, body mass index, smoking, diabetes, beta blocker use, and cardiopulmonary history.
Results
MeanNN, SDNN, and SDANN were significantly and inversely associated with CRP and IL-6 levels in age-adjusted models and after adjustment for all covariates (p ≤ 0.02). MeanNN, SDNN, and SDANN were also inversely associated with fibrinogen levels in age-adjusted models (p < 0.03), but not significantly so in multivariable-adjusted models. Reduced vagal modulation of heart rate (RMSSD) was not significantly associated with any inflammatory measures.
Conclusions
Reduced cardiac autonomic control is associated with increased systemic inflammation in patients with stable CHD. This relationship was largely independent of important covariates.
doi:10.1007/s00392-010-0236-5
PMCID: PMC3207966  PMID: 20857123
Autonomic nervous system; Biomarkers; Cardiac autonomic function; Cardiovascular disease; Heart rate variability; Inflammation
25.  The Relationship among Pulse Wave Velocity, Ankle-Brachial Pressure Index and Heart Rate Variability in Adult Males 
Korean Journal of Family Medicine  2011;32(7):406-411.
Background
Pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) are non-invasive tools to measure atherosclerosis and arterial stiffness. Heart rate variability (HRV) has proven to be a non-invasive powerful tool in the investigation of the autonomic cardiovascular control. Therefore, the purpose of this study was to determine the relationship among PWV, ABI, and HRV parameters in adult males.
Methods
The study was carried out with 117 males who visited a health care center from April, 2009 to May, 2010. We conducted blood sampling (total cholesterol, triglyceride, high density lipoprotein, cholesterol, fasting glucose) and physical examination. We studied brachial-ankle PWV (baPWV) and ABI. We examined HRV parameters including standard deviation of NN interval (SDNN), low frequency (LF), high frequency (HF), LF/HF ratio. We analyzed the relationship among baPWV, ABI, and HRV parameters.
Results
SDNN had a significant negative correlation with age, systolic blood pressure and heart rate. LF and HF had a significant negative correlation with age, and age and heart rate, respectively. baPWV was significantly and positively associated with age, systolic and diastolic blood pressures, total cholesterol, fasting glucose and heart rate. ABI was negative correlated significantly with systolic and diastolic blood pressures and heart rate. After adjusting for all associated variables, baPWV was not correlated with HRV parameters, but there was a significant positive association between SDNN and ABI (r = 0.195, P = 0.014).
Conclusion
SDNN of HRV parameters had a significant positive correlation with ABI.
doi:10.4082/kjfm.2011.32.7.406
PMCID: PMC3383151  PMID: 22745879
Heart Rate Variability; Pulse Wave Velocity; Ankle-Brachial Pressure Index

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