Editor's Note: Commentary based on Gottlieb DJ, Punjabi NM, Mehra R, et al. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med 2014;370:2276-85.

Background

Obstructive sleep apnea (OSA) is a common disorder affecting a quarter of adults at risk, with important cardiovascular sequelae of hypertension, arrhythmias, heart failure, coronary artery disease and stroke. Mechanistic studies have revealed several putative pathways involved in the causation of these adverse associations. Mechanistic studies reveal that hypoxemia during the apnea-hypoapnea cycle plays a crucial role in upregulating the sympathetic nervous activity, worsening the oxidative stress and triggering the inflammatory cascade leading to endothelial dysfunction. Authors of this study hypothesized whether or not there was any benefit of simply using nocturnal supplemental oxygen in comparison to the standard of care continuous positive airway pressure (CPAP) use.

Methods

The primary aim of the study was to measure any difference in 24-hour mean blood pressure (BP) control. The study also sought to assess the impact of each strategy on markers of inflammation and endothelial dysfunction. 318 patients (ages 45-75 years), were identified from cardiology practices across four major enrolling centers by means of Berlin questionnaire and were randomized. The baseline sleep study conducted at home included patients with apnea-hypoapnea index (AHI) of 15-50, excluding severe OSA patients with AHI >50 or oxygen desaturation <85%. The study stratified 106 patients into each, a control group that received healthy lifestyle and sleep education (HLSE) versus two active intervention groups that either received CPAP with HLSE or continuous supplemental oxygen with HLSE. Outcomes were assessed at 12 weeks from randomization.

Results

Complete data was available and analyzed in 281 patients. Patients had similar baseline characteristics, with good control of BP in all the groups. Mean duration of oxygen use (4.8±2.4 hours) was significantly greater than the duration of CPAP use (3.5±2.7 hours), (P=0.001). The duration of hypoxemia reduction was similar in the supplemental oxygen and the CPAP groups, which was significantly greater than the control group. The CPAP group demonstrated a significantly lower adjusted 24-hour mean arterial pressure in comparison to the supplemental oxygen cohort. There was no significant difference in the primary outcome among the supplemental oxygen and the control groups. The BP control seen in the CPAP group was more pronounced at night. The inflammatory biomarkers and the endothelial dysfunction were similar in the two treatment arms with the exception of C-reactive protein (CRP), which was lower in the CPAP arm.

Conclusion

The study highlighted that use of CPAP was associated with reduction in the 24-hour mean arterial BP in moderate-to-severe OSA patients. Supplemental oxygen use had a BP response similar to the control group.

Commentary/Perspective

Improved BP control that could result in measurable improvement in cardiovascular morbidity and mortality is a well studied outcome in the treatment of OSA patients with CPAP. At the same time, lack of compliance and adherence to prolonged use of CPAP over the course of the night is a real world problem. This study importantly shows the relevance of CPAP use and its impact on lowering BP despite only a modest adherence level, which is consistent with real world practices. On the contrary, supplemental oxygen use that had greater compliance was not associated with any beneficial BP reduction, thus challenging the earlier mechanistic studies and raising several questions regarding the alternative pathways (intrathoracic pressure changes, hypercapnia, and arousal) involved in the interaction between OSA and hypertension control. Greater nightly BP reduction despite a lower adherence level begs the question whether some CPAP use is better than no CPAP use, particularly in patients with poor compliance as currently the reimbursement policy restricts the prescription of CPAP in this group of patients. The improvement in CRP levels in the CPAP group is encouraging, albeit in the absence of association of any other inflammatory markers and high burden of cardiovascular risks in this population, it is best to reserve judgment until further data is available.

---

References

1. Gottlieb DJ, Punjabi NM, Mehra R, et al. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med 2014;370:2276-85.
2. Bazzano LA, Khan Z, Reynolds K, He J. Effect of nocturnal nasal continuous positive airway pressure on blood pressure in obstructive sleep apnea. Hypertension 2007;50:417-23.
3. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342:1378-84.

Keywords: Apnea, Arrhythmias, Cardiac, Continuous Positive Airway Pressure, Coronary Artery Disease, Coronary Disease, Heart Failure, Hypertension, Oxidative Stress, Oxygen, Sleep Apnea, Obstructive, Standard of Care, Stroke

< Back to Listings