Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome—Implications for Cardiovascular Risk

Study Objectives:

Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of OSA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome.

Design:

Prospective clinical study.

Participants:

We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18).

Measurements:

OSA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations.

Results:

MSNA (34 ± 2 vs 28 ± 1 bursts/min, P = 0.02) and mean BP (111 ± 3 vs. 99 ± 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-OSA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 ± 0.6 vs 12.2 ± 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 ± 0.6 vs 11.9 ± 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = −0.38, P = 0.04).

Conclusion:

Patients with MetSyn and comorbid OSA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without OSA. These adverse cardiovascular and autonomic consequences of OSA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Citation:

Trombetta IC; Somers VK; Maki-Nunes C; Drager LF; Toschi-Dias E; Alves MJNN; Fraga RF; Rondon MUPB; Bechara MG; Lorenzi-Filho G; Negrão CE. Consequences of comorbid sleep apnea in the metabolic syndrome—implications for cardiovascular risk. SLEEP 2010;33(9):1193-1199.     

Autonomic control of the cardiovascular system during sleep in normal subjects

The autonomic control of heart rate and blood pressure during sleep is controversial: although it has been reported that vagal activity is more often lower in rapid eye movement sleep (REM) than in other stages of sleep (non-REM, NREM), the opposite has also been described. Initially, it was reported that baroreflex sensitivity (BRS) increases during sleep (REM and NREM), but in later studies, this was only partially confirmed. We therefore studied autonomic control of the cardiovascular (CV) system during sleep in 12 normal adults. The spectral components of the heart rate R-R interval, blood pressure (BP), and BRS were computed at low (LF) and actual breathing frequency (high frequency, HF). Analysis of sleep stage and a cycle-by-cycle stage II analysis were performed. CV variability is affected largely by sleep-stage and sleep-cycle organisation: NREM and the last cycle exhibit the greatest vagal activity and the lowest sympathetic activity. BRS estimation for both the LF and HF bands confirmed previous results obtained by pharmacological and spontaneous slope methods: BRS is greater during sleep than during nocturnal wake periods, and further increased in REM. BRS is frequency dependent: in NREM, the higher value of HF BRS compared to LF BRS favours the HF control of BP variability, whereas higher BRS HF and LF components contribute to the strongest control in REM. BRS variability exhibits no significant pattern during the night. Our results suggest that both sleep-cycle organisation and BRS estimation in the LF and HF bands should be considered in sleep studies of autonomic CV control. Electronic Publication     

Effects of feeding schedule changes on the circadian phase of the cardiac autonomic nervous system and serum lipid levels

Purpose

The purpose of this study was to investigate whether scheduling meals earlier in the day affects the circadian phase of the cardiac autonomic nervous system as assessed by heart rate variability (HRV) and serum lipid levels.

Methods

Healthy men aged 21.4 ± 0.5 years (n = 14) with a habit of regularly skipping breakfast participated in this parallel trial involving altered feeding schedules. Participants in the early mealtime group (EM group, n = 8) were asked to eat three meals at 8:00, 13:00, and 18:00, and the control group (n = 6) ate at 13:00, 18:00, and 23:00 for 2 weeks. On the measurement day before and after intervention, fasting blood samples and 24-h electrocardiograph recordings were collected. Spectral analysis was used for approximate 10-min HRV segments. Low frequency (LF) power, high frequency (HF) power, and the ratio of HF to total power (%HF) were calculated to assess sympathovagal balance. Acrophases of the circadian rhythm of HRV variables were obtained by nonlinear least squares regression.

Results

Triglyceride and total and LDL cholesterol levels were significantly decreased in the EM group when compared with the control group (p = 0.035, 0.008, and 0.004, respectively). Acrophases for HRV variables were advanced in the EM group and their difference between before and after the intervention in LF power (?3.2 ± 1.2 h) and %HF (?1.2 ± 0.5 h) reached significant level, respectively (p < 0.05).

Conclusions

Timing of meals was a key factor in regulating circadian phases of the cardiac autonomic nervous system and lipid metabolism.     

Features of autonomic cardiovascular control during cognition in major depressive disorder

Previous research has suggested reduced parasympathetic cardiac regulation during cognitive activity in major depressive disorder (MDD). However, little is known about possible abnormalities in sympathetic control and cardiovascular reactivity. This study aimed to provide a comprehensive analysis of autonomic cardiovascular control in the context of executive functions in MDD. Thirty six MDD patients and 39 healthy controls participated. Parameters of sympathetic (pre‐ejection period, PEP) and parasympathetic control (high and low frequency heart rate variability, HF HRV, LF HRV; and baroreflex sensitivity, BRS) as well as RR interval were obtained at rest and during performance of executive function tasks (number‐letter task, n‐back task, continuous performance test, and Stroop task). Patients, as compared to controls, exhibited lower HF HRV and LF HRV during task execution and smaller shortenings in PEP and RR interval between baseline and tasks. They displayed longer reaction times during all conditions of the tasks and more omission errors and false alarms on the continuous performance test. In the total sample, on‐task HF HRV, LF HRV and BRS, and reactivity in HF HRV, LF HRV, and PEP, were positively associated with task performance. As performance reduction arose independent of executive function load of the tasks, the behavioral results reflect impairments in attention and processing speed rather than executive dysfunctions in MDD. Abnormalities in cardiovascular control during cognition in MDD appear to involve both divisions of the autonomic nervous system. Low tonic parasympathetic control and blunted sympathetic reactivity imply reduced physiological adjustment resources and, by extension, provide suboptimal conditions for cognitive performance.     

Consistent interindividual increases or decreases in muscle sympathetic nerve activity during experimental muscle pain

We recently showed that long-lasting muscle pain, induced by intramuscular infusion of hypertonic saline, evoked two patterns of cardiovascular responses across subjects: one group showed parallel increases in muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate, while the other group showed parallel decreases. Given that MSNA is consistent day to day, we tested the hypothesis that individuals who show increases in MSNA during experimental muscle pain will show consistent responses over time. MSNA was recorded from the peroneal nerve, together with blood pressure and heart rate, during an intramuscular infusion of hypertonic saline causing pain for an hour in 15 subjects on two occasions, 2–27 weeks apart. Pain intensity ratings were not significantly different between the first (5.8 ± 0.4/10) and second (6.1 ± 0.2) recording sessions. While four subjects showed significant decreases in the first session (46.6 ± 9.2 % of baseline) and significant increases in the second (159.6 ± 8.9 %), in 11 subjects, there was consistency in the changes in MSNA over time: either a sustained decrease (55.6 ± 6.8 %, n = 6) or a sustained increase (143.5 ± 6.1 %, n = 5) occurred in both recording sessions. There were no differences in pain ratings between sessions for any subjects. We conclude that the changes in MSNA during long-lasting muscle pain are consistent over time in the majority of individuals, reflecting the importance of studying interindividual differences in physiology.     

Pathological baroreceptor sensitivity in patients suffering from somatization disorders: Do they correlate with symptoms?

Aim

We conducted a study to investigate whether patients with somatization disorders (ICD-10, F45.0) show abnormal values in autonomic testing.

Method

35 patients with a diagnosis of somatization disorder (SP) were matched to 35 healthy volunteers (HV). International standardized autonomic testing based on heart rate variation and continuously measured blood pressure signals was used to assess autonomic activity and establish baroreceptor sensitivity (BRS). Three different statistical procedures were used to confirm the reliability of the findings.

Results

There were no statistical differences between the 2 groups in age, BMI, systolic and diastolic blood pressures, and spectral values (total power, low, and high frequency power). However, heart rate was higher (p = 0.044) and baroreceptor sensitivity was lower (p = 0.002) in the patients compared to the healthy volunteers. Median BRS (±S.E.M.) of patients was 9.09 ± 0.65 compared to 12.04 ± 0.94 ms/mmHg in healthy volunteers. Twenty-two of the 35 patients had a BRS of −1.0S.D. below the mean of HV. SP with lower values differed from SP with normal BRS in values of total power, low-, mid-, and high-frequency bands (p < 0.01 to <0.0001). No differences in psychometric testing were found between patients with lower or higher BRS. In addition, no correlation whatsoever was found in relation to autonomic variables between HV and SP, except for a higher LF/HF quotient in the latter (p < 0.05).

Conclusion

Autonomic regulation was impaired in 62% of patients with a somatization disorder. Severity of clinical symptoms measured by psychometric instruments did not preclude autonomic function impairment. Accordingly, autonomic dysfunction may constitute an independent somatic factor in this patient group.     

Impact of chronic obstructive pulmonary disease on linear and nonlinear dynamics of heart rate variability in patients with heart failure

The objective of this study was to investigate the impact of chronic obstructive pulmonary disease (COPD)-heart failure (HF) coexistence on linear and nonlinear dynamics of heart rate variability (HRV). Forty-one patients (14 with COPD-HF and 27 HF) were enrolled and underwent pulmonary function and echocardiography evaluation to confirm the clinical diagnosis. Heart rate (HR) and R-R intervals (iRR) were collected during active postural maneuver (APM) [supine (10 min) to orthostasis (10 min)], respiratory sinus arrhythmia maneuver (RSA-M) (4 min), and analysis of frequency domain, time domain, and nonlinear HRV. We found expected autonomic response during orthostatic changes with reduction of mean iRR, root mean square of successive differences between heart beats (RMSSD), RR tri index, and high-frequency [HF (nu)] and an increased mean HR, low-frequency [LF (nu)], and LF/HF (nu) compared with supine only in HF patients (P<0.05). Patients with COPD-HF coexistence did not respond to postural change. In addition, in the orthostatic position, higher HF nu and lower LF nu and LF/HF (nu) were observed in COPD-HF compared with HF patients. HF patients showed an opposite response during RSA-M, with increased sympathetic modulation (LF nu) and reduced parasympathetic modulation (HF nu) (P<0.05) compared with COPD-HF patients. COPD-HF directly influenced cardiac autonomic modulation during active postural change and controlled breathing, demonstrating an autonomic imbalance during sympathetic and parasympathetic maneuvers compared with isolated HF.     

Psychophysiological Responses to Emotional Stimuli in Children and Adolescents with Autism and Fragile X Syndrome

Individuals with autism demonstrate atypical and variable responses to social and emotional stimuli, perhaps reflecting heterogeneity of the disorder. The goal of this study was to determine whether unique profiles of psychophysiological responses to such stimuli could be identified in individuals diagnosed with autism spectrum disorder (ASD), with fragile X syndrome (FXS), and with comorbid autism and fragile X syndrome (ASD + FXS), and in typically developing (TYP) individuals. This study included 52 boys (ages 10–17): idiopathic ASD (n = 12), FXS (n = 12), comorbid ASD + FXS (n = 17), and TYP (n = 11). Physiological responses, including potentiated startle, electrodermal response, heart rate variability, and vagal tone, were collected concurrently while participants viewed emotionally evocative pictures of human faces or nonsocial images. Although some of these measures have been utilized separately for investigations on these diagnostic groups, they have not been considered together. Results using Kruskal-Wallis one-way analysis of variance by ranks indicate statistically significant differences in distributions of autonomic regulation responses between groups. The most notable differences were between the ASD group and both the FXS groups on measures of sympathetic activity, with FXS groups evincing increased activity. Also, both the ASD and ASD + FXS groups showed significantly decreased parasympathetic activity compared with FXS and TYP groups. In addition, the ASD + FXS group demonstrated a unique distribution of startle potentiation and arousal modulation. This study provides evidence that autonomic arousal and regulation profiles could be useful for distinguishing subgroups of autism and shed light on the variability underlying emotional responsivity.     

Ventricular and autonomic benefits of exercise training persist after detraining in infarcted rats

We evaluate the effects of detraining (DT, for 1 month) on the left ventricular (LV) remodeling and function, hemodynamic and baroreflex sensitivity (BRS), as well as on mortality rate of infarcted (MI) rats after 3 months of exercise training (ET, 50–70 % of VO_2max). Male Wistar rats were divided into five groups: control (C, n = 10), untrained-infarcted (UI, n = 15), trained-infarcted (TI, n = 12), untrained-infarcted plus 1 month (UI-1, n = 15) and detrained-infarcted 1 month (DI-1, n = 15). LV function was evaluated by echocardiography at the initial and final of the protocols. After following, ET and/or DT protocols, hemodynamic and BRS [by tachycardic (TR) and bradycardic (BR) responses] were assessed. TI group displayed increased VO_2max in comparison with UI and DI-1 groups; however, DI-1 values remained increased compared to UI-1 group. MI area was reduced by ET and maintained after DT. Ejection fraction (TI = 60 ± 2 and DI-1 = 61 ± 2 % vs. UI = 41 ± 1 and UI-1 = 37 ± 3 %), E/A ratio (TI = 1.6 ± 0.1 and DI-1 = 1.9 ± 0.1 vs. UI = 2.9 ± 0.2 and UI-1 = 2.9 ± 0.3), TR (TI = 3.3 ± 0.3 and DI-1 = 3.3 ± 0.4 vs. UI = 1.7 ± 0.1 and UI-1 = 1.6 ± 0.1 bpm/mmHg) and BR (TI = ?2.2 ± 0.1 and DI-1 = ?2.0 ± 0.1 vs. UI = ?1.3 ± 0.09 and UI-1 = ?1.2 ± 0.09 bpm/mmHg) were improved by ET and maintained after DT in comparison with untrained rats. These changes resulted in mortality reduction in the TI (8 %) and DI-1 groups (13 %) compared with the UI (46 %) and UI-1 (53 %) groups. These findings indicate that ET is not only an effective tool in the management of cardiovascular and autonomic MI derangements, but also that these positive changes were maintained even after 1 month of DT in rats.     

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p < 0.01), but metabolic stress-specific alterations were not apparent. There was a trend for increased absolute high-frequency (HF) power (p = 0.10) whereas both absolute low-frequency (LF) power (p = 0.05) and overall power (p = 0.02) were increased to a similar degree following both training programmes. Non-linear heart rate dynamics such as detrended fluctuation analysis $({| {1 - \alpha_{1} }|})$ also improved (p > 0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress.     

Vestibular modulation of muscle sympathetic nerve activity by the utricle during sub-perceptual sinusoidal linear acceleration in humans

We assessed the capacity for the vestibular utricle to modulate muscle sympathetic nerve activity (MSNA) during sinusoidal linear acceleration at amplitudes extending from imperceptible to clearly perceptible. Subjects (n = 16) were seated in a sealed room, eliminating visual cues, mounted on a linear motor that could deliver peak sinusoidal accelerations of 30 mG in the antero-posterior direction. Subjects sat on a padded chair with their neck and head supported vertically, thereby minimizing somatosensory cues, facing the direction of motion in the anterior direction. Each block of sinusoidal motion was applied at a time unknown to subjects and in a random order of amplitudes (1.25, 2.5, 5, 10, 20 and 30 mG), at a constant frequency of 0.2 Hz. MSNA was recorded via tungsten microelectrodes inserted into muscle fascicles of the common peroneal nerve. Subjects used a linear potentiometer aligned to the axis of motion to indicate any perceived movement, which was compared with the accelerometer signal of actual room movement. On average, 67 % correct detection of movement did not occur until 6.5 mG, with correct knowledge of the direction of movement at ~10 mG. Cross-correlation analysis revealed potent sinusoidal modulation of MSNA even at accelerations subjects could not perceive (1.25–5 mG). The modulation index showed a positive linear increase with acceleration amplitude, such that the modulation was significantly higher (25.3 ± 3.7 %) at 30 mG than at 1.25 mG (15.5 ± 1.2 %). We conclude that selective activation of the vestibular utricle causes a pronounced modulation of MSNA, even at levels well below perceptual threshold, and provides further evidence in support of the importance of vestibulosympathetic reflexes in human cardiovascular control.     

Modulation of muscle sympathetic nerve activity by low-frequency physiological activation of the vestibular utricle in awake humans

We recently showed that selective stimulation of one set of otolithic organs—those located in the utricle, sensitive to displacement in the horizontal axis—causes a marked entrainment of skin sympathetic nerve activity (SSNA). Here, we assessed whether muscle sympathetic nerve activity (MSNA) is similarly modulated. MSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in 12 awake subjects, seated (head vertical, eyes closed) on a motorised platform. Slow sinusoidal accelerations–decelerations (±4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at 0.08 Hz. Cross-correlation analysis revealed partial entrainment of MSNA: vestibular modulation was 32 ± 3 % for displacements in the X-axis and 29 ± 3 % in the Y-axis; these were significantly smaller than those evoked in SSNA (97 ± 3 and 91 ± 5 %, respectively). For each sinusoidal cycle, there were two peaks of modulation—one associated with acceleration as the platform moved forward or to the side and one associated with acceleration in the opposite direction. We believe the two peaks reflect inertial displacement of the stereocilia within the utricle during sinusoidal acceleration, which evokes vestibulosympathetic reflexes that are expressed as vestibular modulation of MSNA as well as of SSNA. The smaller vestibular modulation of MSNA can be explained by the dominant modulation of MSNA by the arterial baroreceptors.     

Sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks in noncirrhotic subjects chronically infected with hepatitis C virus genotype 1: a randomized clinical trial

Objective

To investigate the efficacy and safety of sofosbuvir (SOF) plus daclatasvir (DCV) or simeprevir (SMV) in a randomized, open-label, noninferiority trial of patients infected with hepatitis C virus genotype 1, who were previously unresponsive to pegylated interferon and ribavirin or were treatment naive.

Autonomic activity and baroreflex sensitivity in patients submitted to carotid stenting

Arterial baroreflex and cardiac autonomic control play important roles in hemodynamic instability after carotid artery stenting (CAS). Spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and blood pressure variability (BPV) are established tools for the assessment of arterial baroreflex and cardiac autonomic activity. Aim of the study was to evaluate cardiac autonomic activity (by means of HRV, BPV and BRS) after CAS and to explore the impact of internal carotid artery stenosis on BRS changes after CAS. 37 patients (68±10.45 years) with internal carotid stenosis underwent CAS. HRV, BPV and BRS were measured in all subjects before and at 1 and 72h after CAS. ANOVA was performed to compare BRS, HRV and BPV parameters before and after CAS. Spearman analysis was performed to determine a possible correlation between carotid stenosis degree (or carotid plaque diameter) and BRS changes (ΔBRS). LF/HF (index of sympatho-vagal balance) decreased during postoperative period, in comparison with baseline (2.32±1.70 vs 1.65±1.40, p<0.05). There was a significant negative correlation between carotid stenosis degree and ΔBRS (r=-0.35, p=0.03) and between carotid plaques thickness and ΔBRS (r=-0.36, p=0.02). CAS procedure may cause an alteration of carotid wall mechanical properties, increasing baroreflex sensitivity. BRS does not increase in all the patients, because arterial wall damage and nerve destruction determined by atherosclerotic plaque may reduce ΔBRS.     

Differential effect of head-up tilt on cardiovagal and sympathetic baroreflex sensitivity in humans

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat-by-beat R-R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head-up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R-R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R-R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 +/- 2 ms mmHg(-1) versus 7.6 +/- 1.2 ms mmHg(-1); P < 0.01). In contrast, sympathetic BRS increased from -6.1 +/- 1.4 a.u. mmHg(-1) in Supine to -14 +/- 2 a.u. mmHg(-1) in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex-mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading.     

Signs of sympathetic dominance in sleep and wake based on spectral analysis of heart rate variability in children with obstructive sleep apnea

Background

The low- to high-frequency components ratio (LF/HF) of heart rate variability reflects the balance between sympathetic and parasympathetic activity. The autonomic response in individuals with obstructive sleep apnea (OSA) may lead to sympathetic activation demonstrated by an increase in the LF/HF ratio. Studies examining autonomic function during sleep and wake in children with OSA are relatively scarce.

Aim

A meta-analysis of the relevant available publications.

Methods

A MEDLINE search from 2000 through 2013 at PubMed (NLM) was performed. A search for the index terms (“sleep disordered breathing” OR “obstructive sleep apnea”) AND “heart rate” in all fields was done. Studies that included comparisons between children with and without diagnosed OSA were included into the analysis. Types of “outcome measures” were the values of the LF/HF indices in different states of the sleep–wake cycle.

Results

Four studies met the inclusion criteria. A total of 518 control children and 272 children with different degrees of OSA whose mean age ranged between 4.2 and 9.8 years were reported in the studies. Large inconsistencies concerning the effect sizes across publications were found. Meta-regression revealed a statistically significant association between calculated values of the effect sizes and the reported mean values of the apnea–hypopnea indices in the OSA groups (intercept: ??0.11826, regression coefficient: 0.01667, p?=?0.048).

Conclusion

Power analysis of heart rate variability in children with OSA may help to provide further information regarding neural control mechanisms that are altered in OSA. The LF/HF index may serve as an indicator of OSA severity and as a possible marker for risk stratification in children with OSA.     

Autonomic dysfunction and arterial stiffness in female overactive bladder patients and antimuscarinics related effects

Objectives

To investigate the characteristics of autonomic function and arterial stiffness of OAB women, their relations with urodynamic parameters, and the impact of antimuscarinics on the above parameters.

Study design

A total of 85 OAB women and another 65 women without OAB were selected. Forty-two OAB women who enrolled before March 2009 were treated with tolterodine for 12 weeks, and another 43 OAB women who enrolled thereafter were treated with solifenacin.

Main outcome measures

The differences of the heart rate variability, cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI) between OAB and asymptomatic women, and their changes after 12 weeks’ antimuscarinics for OAB women.

Results

OAB women had higher low frequency/high frequency ratios (LF/HF) (OAB: 1.5 ± 1.1 vs. the control: 1.1 ± 0.7, P = 0.04). Nonetheless, CAVI and ABI did not differ between OAB and the control group. The square root of the mean squared differences of successive NN intervals (RMSSD) is associated with nocturia (Spearman's ρ = 0.23, P = 0.049), LF is associated with urgency episodes (Spearman's ρ = 0.28, P = 0.01), and maximum urethral closure pressure is negatively associated with CAVI (Spearman's ρ = −0.26, P = 0.02). After 12 weeks’ treatment, a decrease of RMSSD, HF, CAVI and an increase of LF/HF were found in the tolterodine group but not in the solifenacin group.

Conclusions

OAB women have higher severity of autonomic dysfunction with sympathetic predominance. Tolterodine may improve arterial stiffness but may deteriorate autonomic dysfunction to more sympathetic predominance. Thus, tolteridine should be used for OAB with caution in women with preexisting symptoms of autonomic dysfunction.     

Recovery of heart rate variability after treadmill exercise analyzed by lagged Poincaré plot and spectral characteristics

The aim of this study was to analyze the recovery of heart rate variability (HRV) after treadmill exercise and to investigate the autonomic nervous system response after exercise. Frequency domain indices, i.e., LF(ms²), HF(ms²), LF(n.u.), HF(n.u.) and LF/HF, and lagged Poincaré plot width (SD1 _m ) and length (SD2 _m ) were introduced for comparison between the baseline period (Pre-E) before treadmill running and two periods after treadmill running (Post-E1 and Post-E2). The correlations between lagged Poincaré plot indices and frequency domain indices were applied to reveal the long-range correlation between linear and nonlinear indices during the recovery of HRV. The results suggested entirely attenuated autonomic nervous activity to the heart following the treadmill exercise. After the treadmill running, the sympathetic nerves achieved dominance and the parasympathetic activity was suppressed, which lasted for more than 4 min. The correlation coefficients between lagged Poincaré plot indices and spectral power indices could separate not only Pre-E and two sessions after the treadmill running, but also the two sessions in recovery periods, i.e., Post-E1 and Post-E2. Lagged Poincaré plot as an innovative nonlinear method showed a better performance over linear frequency domain analysis and conventional nonlinear Poincaré plot.     

Effects of deep and superficial experimentally induced acute pain on muscle sympathetic nerve activity in human subjects

Human studies conducted more than half a century ago have suggested that superficial pain induces excitatory effects on the sympathetic nervous system, resulting in increases in blood pressure (BP) and heart rate (HR), whereas deep pain is believed to cause vasodepression. To date, no studies have addressed whether deep or superficial pain produces such differential effects on muscle sympathetic nerve activity (MSNA). Using microneurography we recorded spontaneous MSNA from the common peroneal nerve in 13 awake subjects. Continuous blood pressure was recorded by radial arterial tonometry. Deep pain was induced by intramuscular injection of 0.5 ml hypertonic saline (5%) into the tibialis anterior muscle, superficial pain by subcutaneous injection of 0.2 ml hypertonic saline into the overlying skin. Muscle pain, with a mean rating of 4.9 ± 0.8 ( s.e.m. ) on a 0–10 visual analog scale (VAS) and lasting on average 358 ± 32 s, caused significant increases in MSNA (43.9 ± 10.0%), BP (5.4 ± 1.1%) and HR (7.0 ± 2.0%) – not the expected decreases. Skin pain, rated at 4.9 ± 0.6 and lasting 464 ± 54 s, also caused significant increases in MSNA (38.2 ± 12.8%), BP (5.1 ± 2.1%) and HR (5.6 ± 2.0%). The high-frequency (HF) to low-frequency (LF) ratio of heart rate variability (HRV) increased from 1.54 ± 0.25 to 2.90 ± 0.45 for muscle pain and 2.80 ± 0.52 for skin pain. Despite the different qualities of deep (dull and diffuse) and superficial (burning and well-localized) pain, we conclude that pain originating in muscle and skin does not exert a differential effect on muscle sympathetic nerve activity, both causing an increase in MSNA and an increase in the LF : HF ratio of HRV. Whether this holds true for longer lasting experimental pain remains to be seen.     

Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes

Power spectral analysis of heart rate variability has often been used to assess cardiac autonomic function; however, the relationship of low-frequency (LF) power of heart rate variability to cardiac sympathetic tone has been unclear. With or without adjustment for high-frequency (HF) power, total power or respiration, LF power seems to provide an index not of cardiac sympathetic tone but of baroreflex function. Manipulations and drugs that change LF power or LF:HF may do so not by affecting cardiac autonomic outflows directly but by affecting modulation of those outflows by baroreflexes.