Circadian Patterns of Heart Rate and Heart Rate Variability in Wake-up Stroke: Evidence of Parasympathetic Dysregulation

Introduction: Although ischemic stroke is associated with complex changes in the autonomic nervous system, the circadian patterns of heart rate (HR) and heart rate variability (HRV) in wake-up stroke (WUS) remain poorly understood. This study compared 24-hour heart rate and HRV patterns between patients with and without WUS. Methods: This retrospective observational case-control study involved 104 patients with acute ischemic stroke (9 WUS, 95 non-WUS). HRV analysis was performed using a 14-day continuous electrocardiography patch monitor. Time- and frequency-domain HRV metrics were calculated, and 24-hour differences were assessed using generalized additive mixed models (GAMMs), adjusting for confounders. Results: WUS patients had significantly higher HRs (80.60 ± 12.49 vs. 73.22 ± 14.49 beats per minute, P < 0.001) and lower HRV-measured by SDNN (28.06 ± 21.68 vs. 39.70 ± 25.73 milliseconds, P < 0.001), RMSSD (15.78 ± 12.49 vs. 22.16 ± 19.22 milliseconds, P < 0.001), and pNN50 (1.03% ± 2.78% vs. 2.61% ± 5.15%, P < 0.001)-than non-WUS patients. GAMMs indicated that patients with WUS experienced significant autonomic dysregulation, characterized by higher HRs, lower HRV, and altered circadian rhythms compared to those with non-WUS. These differences were particularly evident during the early morning hours. Discussion: WUS patients exhibited distinct 24-hour HR and HRV profiles, characterized by higher HRs and reduced autonomic variability compared to non-WUS patients. These differences align with patterns typically associated with lower parasympathetic activity rather than elevated sympathetic tone. Conclusion: WUS is associated with impaired autonomic regulation and disrupted circadian patterns of HR and HRV.