To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.

This study assessed the heritability of ambulatory heart period, respiratory sinus arrhythmia (RSA), and respiration rate and tested the hypothesis that the well-established correlation between these variables is determined by common genetic factors. In 780 healthy twins and siblings, 24-h ambulatory recordings of ECG and thorax impedance were made. Genetic analyses showed considerable heritability for heart period (37%-48%), RSA (40%-55%), and respiration rate (27%-81%) at all daily periods. Significant genetic correlations were found throughout. Common genes explained large portions of the covariance between heart period and RSA and between respiration rate and RSA. During the afternoon and night, the covariance between respiration rate and RSA was completely determined by common genes. This overlap in genes can be exploited to increase the power of linkage studies to detect genetic variation influencing cardiovascular disease risk.

Introduction: Overactivity of the sympathetic nervous system (SNS) plays a pivotal role in the development of cardiovascular disease. This involvement suggests that the genetic susceptibility to adverse cardiovascular events may derive in part from individual differences in SNS activity. Methods and Results: To establish a genetic contribution to SNS activity, we measured sympathetic effects on cardiac contractility in 755 healthy adult twins and their singleton siblings. The preejection period (PEP) and the ratio of PEP to the left ventricular ejection time (PEP/LVET ratio) were derived from ambulatory recordings of the ECG and thorax impedance. During this type of prolonged recordings in a real life setting, the extent of cardiac sympathetic activity will vary with the demands of daily activities. Therefore, the genetic architecture of both indices was examined separately across three daytime periods (morning, afternoon, evening), and during nighttime sleep. Results showed significant genetic contribution to PEP (48–62%) over all daily periods. Heritability estimates for PEP/LVET ratio ranged between 35% and 58%. Cardiac sympathetic activity during the waking and sleep periods was largely influenced by genetic factors that were common to the entire 24-hour period. During sleep, additional genetic influences emerged that accounted for 8% of the variance in PEP. Conclusion: Impedance-derived measures of sympathetic effects on cardiac contractility show substantial heritability across all periods of the day and during sleep.

Recently, devices have become available that allow non-invasive measurement of stroke volume and cardiac output through ambulatory thorax impedance recording. If such recordings have adequate temporal stability, they offer great potential to further our understanding of how repeated or chronic cardiovascular activation in response to naturalistic events may contribute to cardiovascular disease. In this study, 24h ambulatory impedance-derived systolic time intervals, stroke volume and cardiac output were measured in 65 healthy subjects across an average time span of 3 years and 4 months. Stability was computed separately for sleep and daytime recordings. To avoid confounding by differences in posture and physical activity across measurement days, temporal stability was computed using sitting activities only. During the day intraclass correlations were moderate for stroke volume (.29–.46) and cardiac output (.33–.46) and good for systolic time intervals (.55–.81). When test–retest comparison was limited to two comparable days (two work days or two leisure days), correlations for both SV (.42–.46) and CO (.43–.50) improved. Conclusion: Moderate long-term temporal stability is found for individual differences in ambulatory stroke volume and cardiac output measured by impedance cardiography.

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.

Mechanisms relating Type D personality to poor health are largely unknown, with autonomic nervous system function being a candidate. This study examined the physiologic response to cold stress. Undergraduates (N = 101, 84% female) underwent a cold pressor test. An electrocardiogram, impedance cardiogram, and blood pressure were recorded. Type D personality was assessed by self-report questionnaire. Type D was associated with increased systolic and diastolic blood pressure reactivity. Exploratory analyses showed Type D men to respond with increased respiratory sinus arrhythmia (i.e., higher parasympathetic activity), and decreased pre-ejection period (i.e., larger sympathetic activity), while Type D women showed a reciprocal response pattern. In conclusion, Type D personality was associated with an exaggerated hemodynamic response to cold stress, which may contribute to an increased risk of hypertension in Type D individuals.

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.

Background
There are large individual differences in dealing with everyday social stress. Therefore, we investigated the association of social inhibition (and its facets) with the emotional and physiological responses to the Trier Social Stress Test (TSST).
Methods
Undergraduate students (N = 312) completed the 15-item Social Inhibition Questionnaire (SIQ15) and participated in the TSST, while emotional and cardiovascular stress responses were recorded. We examined the effect of social inhibition across time with repeated-measures ANCOVAs.
Findings
During social stress (and recovery), social inhibition was associated with increased negative mood reactivity (especially the behavioral inhibition facet) and heightened sympathetic activation (especially the social withdrawal and interpersonal sensitivity). Physiological stress reactivity seems to be mostly α-adrenergic in women, and also β-adrenergic in men.
Conclusions
Emotional and physiological stress responses are associated with individual differences in social inhibition. This warrants more research on mechanisms that underlie the relations between social inhibition, stress and health.

Objective 
Individual differences in long-term cardiovascular disease risk are related to physiological responses to psychological stress. However, little is known about specific physiological response profiles in young adults that may set the stage for long-term increased cardiovascular disease risk. We investigated individual differences in profiles of resting cardiovascular physiology and stress reactivity, combining parasympathetic, sympathetic, and hemodynamic measures.
Methods 
Participants (n = 744, 71% women, mean [standard deviation] age = 20.1 [2.4] years) underwent the Trier Social Stress Test, while blood pressure (systolic blood pressure, diastolic blood pressure), electrocardiograms (interbeat interval), and impedance cardiograms (preejection period, left ventricular ejection time) were recorded. Respiratory sinus arrhythmia was derived from the combination of the electrocardiogram and the impedance cardiogram. A three-step latent profile analysis (LPA) was performed on resting and reactivity values to derive clusters of individual physiological profiles. We also explored demographic and health behavioral correlates of the observed latent clusters.
Results 
For resting physiology, LPA revealed five different resting physiology profiles, which were related to sex, usual physical activity levels, and body mass index. Five cardiovascular stress reactivity profiles were identified: a reciprocal/moderate stress response (Cr1; 29%), and clusters characterized by high blood pressure reactivity (Cr2: 22%), high vagal withdrawal (Cr3; 22%), autonomic coactivation (parasympathetic nervous system and sympathetic nervous system; Cr4; 13%), and overall high reactivity (Cr5; 12%). Men were more likely to belong to the high reactivity (Cr5) cluster, whereas women were more likely to have autonomic coactivation (Cr4).
Conclusions 
We identified five cardiovascular physiological reactivity profiles, with individuals displaying generalized hyperreactivity, predominant vagal withdrawal, autonomic coactivation, or blood pressure–specific hyperreactivity. Longitudinal studies are needed to determine whether these profiles are useful in early detection of individuals at high risk for cardiovascular disease.