Cardiac Hormesis in Unstable Sleep

초록

Introduction: Hormesis, an adaptive and protective response triggered by milder stress, has been demonstrated across multiple animal models. Controlled or intermittent hypoxia has shown neuroprotective and cardiometabolic benefits. Whether sleeprelated physiological stressors exhibit hormetic effects in humans remains unclear. Methods: We analyzed data from participants in the Korean Genome and Epidemiology Study (KoGES). Seven sleep quality and stability metrics were derived from photoplethysmographybased cardiopulmonary spectrograms obtained during home ambulatory polysomnography: apnea index during REM sleep, mean apnea duration, Sleep Quality Index (SQI), fragmentation (eLFCbb), and the percent of stable sleep, unstable sleep, and REM sleep. ECG-age was estimated using a validated deep-learning model from 12-lead ECG waveforms. Participants were categorized into normal, accelerated, or decelerated aging groups based on the difference between predicted ECG-age and chronological age (within ±5 years; >5 years older; or >5 years younger, respectively). Logistic regression models adjusted for age, sex, and body mass index were used to assess associations between each sleep trait and aging category, with normal aging as the reference. Results: The study included 2,237 participants (mean age of 59±7 years, 50.0% female). Among them, 1,682 (75.2%) were classified as normal aging, 277 (12.4%) as accelerated aging, and 278 (12.4%) as decelerated aging. Higher apnea index during REM sleep, longer mean apnea duration, and a greater proportion of unstable sleep were each associated with lower odds of accelerated aging (OR 0.73, 95% CI 0.62–0.86; OR 0.80, 95% CI 0.69–0.94; OR 0.84, 95% CI 0.72–0.97, respectively). Conversely, a higher proportion of stable sleep was associated with higher odds of accelerated aging (OR 1.24, 95% CI 1.07–1.43). Most sleep traits were not significantly associated with decelerated aging, with the exception of fragmentation (eLFCbb), where higher fragmentation modestly increased the odds of decelerated aging (OR 1.15, 95% CI 1.01–1.32). Conclusion: Several sleep features typically considered undesirable, including higher apnea burden and greater sleep instability, were paradoxically associated with lower electrophysiologic aging. These findings suggest a possible hormetic effect of sleeprelated physiological stress on cardiovascular aging and highlight the need for further mechanistic investigation. Support (if any): Korea National Institute of Health(NIH) research project (project No.2011-E71004-00, 2012-E71005-00, 2013-E71005- 00, 2014-E71003-00) R21HL175584