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.

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.

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.

Objective 
Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers.
Methods 
Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6.
Results 
The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = −.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up.
Conclusions 
Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

Introduction: The resting ECG is the most commonly used tool to assess cardiac electrophysiology. Previous studies have estimated heritability of ECG parameters based on these snapshots of the cardiac electrical activity. In this study we set out to determine whether analysis of heart rate specific data from Holter ECGs allows more complete assessment of the heritability of ECG parameters.Methods and Results: Holter ECGs were recorded from 221 twin pairs and analyzed using a multi-parameter beat binning approach. Heart rate dependent estimates of heritability for QRS duration, QT interval, Tpeak–Tend and Theight were calculated using structural equation modeling. QRS duration is largely determined by environmental factors whereas repolarization is primarily genetically determined. Heritability estimates of both QT interval and Theight were significantly higher when measured from Holter compared to resting ECGs and the heritability estimate of each was heart rate dependent. Analysis of the genetic contribution to correlation between repolarization parameters demonstrated that covariance of individual ECG parameters at different heart rates overlap but at each specific heart rate there was relatively little overlap in the genetic determinants of the different repolarization parameters.Conclusions: Here we present the first study of heritability of repolarization parameters measured from Holter ECGs. Our data demonstrate that higher heritability can be estimated from the Holter than the resting ECG and reveals rate dependence in the genetic—environmental determinants of the ECG that has not previously been tractable. Future applications include deeper dissection of the ECG of participants with inherited cardiac electrical disease.