Method to quantify the impact of sleep on cardiac neuroautonomic functionality: application to the prediction of cardiovascular events in the Multi-Ethnic Study of Atherosclerosis

We introduce the concept of cardiac neuroautonomic renewability and a method for its quantification. This concept refers to the involuntary nervous system’s capacity to improve cardiac control in response to restorative interventions, such as sleep. We used the change in heart rate fragmentation (ΔHRF), before sleep onset compared with after sleep termination, to quantify the restorative effects of sleep. We hypothesized that the ability to improve cardiac neuroautonomic functionality would diminish with age and be associated with lower risk of major adverse cardiovascular events (MACE). We analyzed the ECG channel of polysomnographic recordings from an ancillary investigation of the Multi-Ethnic Study of Atherosclerosis (MESA). In a cohort of 659 participants (mean ± SD age, 69.7 ± 8.8; 42% male), HRF was significantly ( P < 0.001) lower after sleep (before: 74 ± 12%, after: 67 ± 13%). Furthermore, the magnitude of the decrease significantly ( P < 0.001) diminished with cross-sectional age. In addition, a larger reduction in HRF following sleep (i.e., higher ΔHRF) was associated with lower risk of MACE, independent of traditional cardiovascular risk factors and current measures of sleep quality. Specifically, over a mean follow-up period of 6.4 ± 1.6 yr, in which 60 participants had their first MACE, a one-SD (12%) increase in ΔHRF was associated with a 36% (95% CI: 12%–53%) decrease in the risk of MACE. The results demonstrate the restorative impact of sleep on heart rate control. As such they support the concept of cardiac neuroautonomic renewability and the utility of ΔHRF for its quantification.