Treatment with mild intermittent hypoxia and CPAP is most effective in mitigating OSA disease severity and reducing nighttime blood pressure

Objective: Blood pressure reductions during sleep (i.e. dipping) is a healthy occurrence that is mitigated in obstructive sleep apnea (OSA) patients. Our lab has shown that repeated daily exposure to mild intermittent hypoxia (MIH) with nightly continuous positive airway pressure (CPAP) treatment for 15 days can improve both upper airway patency and daytime blood pressure. However, we did not determine if reductions in OSA disease severity are associated with improvements in nighttime blood pressure. In the present investigation, we determined if the combined treatment of MIH and nightly CPAP is most effective in improving OSA disease severity (i.e. apnea hypopnea index [AHI]) and reducing blood pressure during sleep. Methods: 27 participants with OSA and hypertension have been enrolled in our study and were randomized into one of four groups: Group 1 - MIH + CPAP (6M, 1F), Group 2 - CPAP alone (6M, 1F), Group 3 - MIH alone (5M, 1F) and Group 4 - no intervention (6M, 1F). Measurements of disease severity (i.e. AHI) were obtained from a full night polysomnogram study without CPAP treatment before, 4 4 days, 4 weeks and 8 weeks after treatment. Prior to each sleep study, 24-hour blood pressure was measured utilizing a Holter monitor that was programmed to obtain blood pressure readings every 20 minutes. Participants receiving MIH were exposed to 12 – 2 minute episodes of hypoxia (P ET O 2 maintained at ~ 50 mmHg) interspersed with room air. Following an initial 10-minute normoxic baseline, participants were exposed to CO 2 elevated 2 mmHg above baseline for the remainder of the study. Participants in Group 2 and 4 were exposed to compressed air during “hypoxic” trials but were otherwise breathing room air. Results: Baseline measures of age (46.59 ± 9.38 years, p > 0.80), BMI (33.14 ± 4.88 kg/m 2 , p > 0.50), and mean arterial pressure (102.51 ± 7.07 mmHg, p > 0.40) were similar in Groups 1 - 4. Participants in Group 1 experienced a reduction in mean arterial pressure (MAP) during sleep immediately following treatment (91.95 ± 10.15 mmHg vs. 83.64 ± 8.81 mmHg, p < 0.05) that was maintained for 8 weeks (4 week: 84.15 ± 9.24 mmHg, p < 0.05; 8 week: 86.10 ± 7.51 mmHg, p < 0.05). In addition, a reduction in blood pressure was evident in Group 3 participants for a shorter period (i.e. 4 weeks) (baseline: 88.09 ± 7.23 mmHg; 4 days: 81.15 ± 7.69 mmHg, p < 0.06 d = 0.93; 4 weeks: 80.12 ± 8.88 mmHg p < 0.05). Moreover, participants in group 1 experienced a higher reduction in blood pressure at 4 and 8 weeks after treatment compared to group 3 participants (4 week: -5.08 ± 4.81 vs. 3.01 ± 8.05 mmHg; 8 week: -9.72 ± 5.59 vs. 6.22 ± 12.24 mmHg; p < 0.05). Likewise, group 1 experienced an improvement in AHI at 4 days (69.36 ± 22.23 events/hour vs. 59.44 ±26.50 events/hour; p = 0.15, d = 0.41) and 4 weeks (56.14 ± 29.75 events/hour; p < 0.05) following treatment. The reduction in AHI may have been linked to changes in the arousal threshold, since an increase in the ventilatory arousal threshold was associated with a higher reduction in blood pressure (R 2 = 0.56, p < 0.05). No modifications in AHI or blood pressure were evident in Groups 2-4. Conclusions: The combined treatment of MIH and CPAP is most effective in reducing blood pressure during sleep compared to MIH or CPAP alone. Additionally, improvements in the ventilatory arousal threshold may be an underlying mechanism mediating reductions in AHI and blood pressure. J.H.M. is supported by the United States Department of Veterans Affairs (I01CX000125, IK6CX002287) and the National Institute of Heart, Lung and Blood (R01HL085537) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.