Background— Reduced heart rate variability (HRV) is a prognostic factor for cardiac disease and cardiac mortality. Understanding the sources of individual differences in HRV may increase its diagnostic use and provide new angles for preventive therapy. To date, the contribution of genetic and environmental factors to the variance in HRV has not been investigated during prolonged periods of ambulatory monitoring in a naturalistic setting.

Methods and Results— In 772 healthy twins and singleton siblings, ambulatory ECG was recorded during 24 hours. Two time domain measures of HRV were used: the standard deviations of all normal-to-normal intervals across 5-minute segments (SDNN index) and the root mean square of successive differences between adjacent normal RR intervals (RMSSD). Multivariate genetic analyses across 4 periods of day (morning, afternoon, evening, night) yielded significant estimates for genetic contribution to the mean ambulatory SDNN index (ranging from 35% to 47%) and the mean ambulatory RMSSD (ranging from 40% to 48%).

Conclusions— Ambulatory HRV measures are highly heritable traits that can be used to support genetic association and linkage studies in their search for 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.

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.

Large individual differences exist in aerobic fitness in childhood and adolescence, but the relative contribution of genetic factors to this variation remains to be established. In a sample of adolescent twins and siblings (n = 479), heart rate (HR) and maximal oxygen uptake (V̇o2max) were recorded during the climax of a graded maximal exercise test. In addition, V̇o2max was predicted in two graded submaximal exercise tests on the cycle ergometer and the treadmill, using extrapolation of the HR/V̇o2 curve to the predicted HRmax. Heritability estimates for measured V̇o2max were 60% in ml/min and 55% for V̇o2max in ml·min−1·kg−1. Phenotypic correlations between measured V̇o2max and predicted V̇o2max from either submaximal treadmill or cycle ergometer tests were modest (0.57 < r < 0.70), in part because of the poor agreement between predicted and actual HRmax. The majority of this correlation was explained by genetic factors; therefore, the submaximal exercise tests still led to very comparable estimates of heritability of V̇o2max. To arrive at a robust estimate for the heritability of V̇o2max in children to young adults, a sample size weighted meta-analysis was performed on all extant twin and sibling studies in this age range. Eight studies, including the current study, were meta-analyzed and resulted in a weighted heritability estimate of 59% (ml/min) and 72% (ml·min−1·kg−1) for V̇o2max. Taken together, the twin-sibling study and meta-analyses showed that from childhood to early adulthood genetic factors determine more than half of the individual differences in V̇o2max.