Obstructive sleep apnea (OSA) is associated with increased cardiometabolic morbidity and mortality. However, randomized controlled trials (RCTs) of continuous positive airway pressure (CPAP) for secondary cardiovascular disease (CVD) prevention have not demonstrated benefit.1 We have identified a “high-CVD-risk” OSA phenotype characterized by respiratory events producing deep oxygen desaturations (high “hypoxic burden”) or large event-related increases in heart rate (high “heart-rate response”). Using data from 3 RCTs of CPAP for secondary prevention of CVD, we found that in high-CVD-risk OSA, CPAP was associated with a 24% to 35% relative reduction in major adverse cardiovascular events compared with usual care.1 In contrast, among “low-CVDrisk” OSA patients (those without high hypoxic burden or heart-rate response) CPAP was associated with a 30% to 35% relative increase in major adverse cardiovascular events. These findings highlight the need to understand the mechanisms by which CPAP may confer cardiovascular benefit in some individuals yet harm in others. One proposed mechanism of CPAP-related harm involves pulmonary distension resulting in release of angiopoietin-2 (ANGPT2) from pulmonary endothelial cells, with a resultant increase in systemic vascular inflammation, as several studies show that CPAP treatment causes an increase in circulating ANGPT2.2-4 In this study, we tested the hypothesis that the CPAP-induced change in ANGPT2 differs by OSA-related CVD risk group.