Heritability and Temporal Stability of Ambulatory Autonomic Stress Reactivity in Unstructured 24-Hour Recordings.

OBJECTIVE: Measurements of ambulatory autonomic reactivity can help with our understanding of the long-term health consequences of exposure to psychosocial stress in real-life settings. METHODS: In this study, unstructured 24-hour ambulatory recordings of cardiac parasympathetic and sympathetic control were obtained in 1288 twins and siblings, spanning both work time and leisure time. These data were used to define two ambulatory baseline (sleep, leisure) and four stress conditions (wake, work, work_sitting, work_peak) from which six ambulatory stress reactivity measures were derived. The use of twin families allowed for estimation of heritability and testing for the amplification of existing or emergence of new genetic variance during stress compared with baseline conditions. RESULTS: Temporal stability of ambulatory reactivity was assessed in 62 participants and was moderate to high over a 3-year period (0.36 < r < 0.91). Depending on the definition of ambulatory reactivity used, significant heritability was found, ranging from 29% to 40% for heart rate, 34% to 47% for cardiac parasympathetic control (indexed as respiratory sinus arrhythmia), and 10% to 19% for cardiac sympathetic control (indexed as the preejection period). Heritability of ambulatory reactivity was largely due to newly emerging genetic variance during stress compared with periods of rest. Interestingly, reactivity to short standardized stressors was poorly correlated with the ambulatory reactivity measures implying poor laboratory-real-life correspondence. CONCLUSIONS: Ambulatory autonomic reactivity extracted from an unstructured real-life setting shows reliable, stable, and heritable individual differences. Real-life situations uncover a new and different genetic variation compared with that seen in resting baseline conditions, including sleep.

A Novel Noninvasive Device to Assess Sympathetic Nervous System Function in Patients With Heart Failure.

BACKGROUND: Heart failure is a complex syndrome associated with sympathetic nervous system and renin-angiotensin-aldosterone system hyperactivity. Sympathoinhibition and downregulation of sympathetic activity using medications and exercise training improve outcomes in patients with heart failure. Impedance cardiography provides data on hemodynamic and autonomic function that may assist with safe medication, exercise monitoring, and titration. PURPOSE: The purpose of this pilot study was to evaluate the sensitivity of the Vrije Universiteit Ambulatory Monitoring System (VU-AMS) version 5fs to detect hemodynamic and sympathetic nervous system changes associated with postural shift in persons with heart failure with reduced ejection fraction. METHODS: In this descriptive study, participants (N = 28) were recruited from an outpatient device clinic at a tertiary care hospital in Ontario, Canada. They completed a sit-to-stand posture protocol wearing an ambulatory blood pressure (ABP) and a noninvasive VU-AMS version 5fs impedance cardiography system. RESULTS: Most (n = 18, 64%) participants were eliminated from the final analyses in this sample because of difficulty in Q-onset and B-point identification in peculiar electrocardiogram and impedance cardiogram waveforms. The remaining participants (n = 10) had a mean age of 69 years (SD = 10 years) and responses to a sit-to-stand posture protocol that included a 5% increase in heart rate (p = .001), an 18% decrease in stroke volume (p = .01), and an 8% decrease in left ventricular ejection time (p = .01). Participants had an increased preejection period (11%, p = .01), a drop in cardiac output of 13% (p = .02), and a reduced mean arterial pressure of approximately 4% (p = .09) with standing. DISCUSSION: Although the VU-AMS version 5fs system detected anticipated hemodynamic and sympathetic nervous system changes to postural shift in participants (n = 10), the elimination of 64% (n = 18) of the sample because of scoring difficulties limits the use of this impedance cardiography device using standard scoring algorithms in persons with heart failure with reduced ejection fraction.

The Adult Netherlands Twin Register: twenty-five years of survey and biological data collection.

Over the past 25 years, the Adult Netherlands Twin Register (ANTR) has collected a wealth of information on physical and mental health, lifestyle, and personality in adolescents and adults. This article provides an overview of the sources of information available, the main research findings, and an outlook for the future. Between 1991 and 2012, longitudinal surveys were completed by twins, their parents, siblings, spouses, and offspring. Data are available for 33,957 participants, with most individuals having completed two or more surveys. Smaller projects provided in-depth phenotyping, including measurements of the autonomic nervous system, neurocognitive function, and brain imaging. For 46% of the ANTR participants, DNA samples are available and whole genome scans have been obtained in more than 11,000 individuals. These data have resulted in numerous studies on heritability, gene x environment interactions, and causality, as well as gene finding studies. In the future, these studies will continue with collection of additional phenotypes, such as metabolomic and telomere length data, and detailed genetic information provided by DNA and RNA sequencing. Record linkage to national registers will allow the study of morbidity and mortality, thus providing insight into the development of health, lifestyle, and behavior across the lifespan.

Ambulatory measurement of the ECG T-wave amplitude.

Ambulatory recording of the preejection period (PEP) can be used to measure changes in cardiac sympathetic nervous system (SNS) activity under naturalistic conditions. Here, we test the ECG T-wave amplitude (TWA) as an alternative measure, using 24-h ambulatory monitoring of PEP and TWA in a sample of 564 healthy adults. The TWA showed a decrease in response to mental stress and a monotonic decrease from nighttime sleep to daytime sitting and more physically active behaviors. Within-participant changes in TWA were correlated with changes in the PEP across the standardized stressors (r = .42) and the unstandardized naturalistic conditions (mean r = .35). Partialling out changes in heart rate and vagal effects attenuated these correlations, but they remained significant. Ambulatory TWA cannot replace PEP, but simultaneous recording of TWA and PEP provides a more comprehensive picture of changes in cardiac SNS activity in real-life settings.

A fluid response: Alpha-amylase reactions to acute laboratory stress are related to sample timing and saliva flow rate.

Salivary alpha-amylase (sAA) is used as a sympathetic (SNS) stress marker, though its release is likely co-determined by SNS and parasympathetic (PNS) activation. The SNS and PNS show asynchronous changes during acute stressors, and sAA responses may thus vary with sample timing. Thirty-four participants underwent an eight-minute memory task (MT) and cold pressor task (CPT). Cardiovascular SNS (pre-ejection period, blood pressure) and PNS (heart rate variability) activity were monitored continuously. Unstimulated saliva was collected repeatedly during and after each laboratory stressor, and sAA concentration (U/ml) and secretion (U/minute) determined. Both stressors increased anxiety. The MT caused an immediate and continued cardiac SNS activation, but sAA concentration increased at task cessation only (+54%); i.e., when there was SNS-PNS co-activation. During the MT sAA secretion even decreased (-35%) in conjunction with flow rate and vagal tone. The CPT robustly increased blood pressure but not sAA. In summary, sAA fluctuations did not parallel changes in cardiac SNS activity or anxiety. sAA responses seem contingent on sample timing and flow rate, likely involving both SNS and PNS influences. Verification using other stressors and contexts seems warranted.

Autonomic Nervous System Responses to Viewing Green and Built Settings: Differentiating Between Sympathetic and Parasympathetic Activity.

This laboratory study explored buffering and recovery effects of viewing urban green and built spaces on autonomic nervous system activity. Forty-six students viewed photos of green and built spaces immediately following, and preceding acute stress induction. Simultaneously recorded electrocardiogram and impedance cardiogram signal was used to derive respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP), indicators of respectively parasympathetic and sympathetic activity. The findings provide support for greater recovery after viewing green scenes, as marked by a stronger increase in RSA as a marker of parasympathetic activity. There were no indications for greater recovery after viewing green scenes in PEP as a marker of sympathetic activity, and there were also no indications of greater buffering effects of green space in neither RSA nor PEP. Overall, our findings are consistent with a predominant role of the parasympathetic nervous system in restorative effects of viewing green space.

Heritability of cardiac vagal control in 24-h heart rate variability recordings: influence of ceiling effects at low heart rates.

This study estimated the heritability of 24-h heart rate variability (HRV) measures, while considering ceiling effects on HRV at low heart rates during the night. HRV was indexed by the standard deviation of all valid interbeat intervals (SDNN), the root mean square of differences between valid, successive interbeat intervals (RMSSD), and peak-valley respiratory sinus arrhythmia (pvRSA). Sleep and waking levels of cardiac vagal control were assessed in 1,003 twins and 285 of their non-twin siblings. Comparable heritability estimates were found for SDNN (46%-53%), RMSSD (49%-54%), and pvRSA (48%-57%) during the day and night. A nighttime ceiling effect was revealed in 10.7% of participants by a quadratic relationship between mean pvRSA and the interbeat interval. Excluding these participants did not change the heritability estimates. The genetic factors influencing ambulatory pvRSA, RMSSD, and SDNN largely overlap. These results suggest that gene-finding studies may pool the different cardiac vagal indices and that exclusion of participants with low heart rates is not required.

Estimated preejection period (PEP) based on the detection of the R-wave and dZ/dt-min peaks does not adequately reflect the actual PEP across a wide range of laboratory and ambulatory conditions.

The current study evaluates the validity of the PEP computed from a fixed value for the Q-wave onset to R-wave peak (QR) interval and an R-wave peak to B-point (RB) interval that is estimated from the R-peak to dZ/dt-min peak (ISTI) interval. Ninety-one subjects participated in a 90min laboratory experiment in which a variety of often employed physical and mental stressors were presented and 31 further subjects participated in a structured 2hour ambulatory recording in which they partook in natural activities that induced large variation in posture and physical activity. PEP, QR interval, and ISTI were scored and rigorously checked by interactive inspection. Across the very diverse laboratory and ambulatory conditions the QR interval could be approximated by a fixed interval of 40ms but 95% confidence intervals were large (25.5 to 54.5ms). Multilevel analysis showed that 79% to 81% of the within and between-subject variation in the RB interval could be predicted by the ISTI with a simple linear regression equation. However, the optimal intercept and slope values in this equation varied significantly across subjects and study setting. Bland Altman plots revealed a large discrepancy between the estimated PEP using the R-wave peak and dZ/dt-min peak and the actual PEP based on the Q-wave onset and B-point. We conclude that the PEP estimated from a fixed QR interval and the ISTI could be a useful addition to the psychophysiologist's toolbox, but that it cannot replace the actual PEP to index cardiac sympathetic control.

Measuring cardiac autonomic nervous system (ANS) activity in children.

The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device (1-5), the VU University Ambulatory Monitoring System (VU-AMS, Amsterdam, the Netherlands, www.vu-ams.nl).

Underestimation of cardiac vagal control in regular exercisers by 24-hour heart rate variability recordings.

OBJECTIVE: To examine whether ceiling effects at long inter beat intervals (IBIs)cause an underestimation of cardiac vagal control in regular exercisers by time and frequency-domain measures of respiratory sinus arrhythmia (RSA). METHODS: 24-hour ECG and respiration recordings were performed in 26 regularly exercising subjects, actively engaged in aerobic training for the past year, and enrolled in supervised training in the six weeks pre-study, and in 26 age- and sex-matched non-exercisers. Sleep and waking levels of cardiac vagal control were estimated by RSA obtained through the peak-valley method, by the standard deviation of the IBIs, the root mean square of successive IBIs, and the high frequency IBI spectral power. RESULTS: In 11 of the exercisers the IBI-RSA relationship was characterized by a quadratic relationship. This reflected a ceiling effect at very long IBI values attained by regular exercisers, particularly during the nighttime recording. Irrespective of this ceiling effect, RSA as well as other heart rate variability (HRV) measures was still significantly larger in the exercisers with a quadratic IBI-RSA relationship than in non-exercisers or exercisers with a linear IBI-RSA relationship. CONCLUSIONS: We conclude that a subgroup of regular exercisers is characterized by a low heart rate paired to high levels of cardiac vagal control. In these exercisers, vagal control is underestimated from HRV measures in ambulatory recordings. Inspection of the IBI-RSA relationship should be routinely added when HRV measures are used to index cardiac vagal control.