Cardiovascular effects of CPAP withdrawal: an RCT post-hoc analysis using hypoxic burden

<bold>Introduction:</bold> Hypoxic burden (HB) estimates obstructive sleep apnoea (OSA)-associated nocturnal intermittent hypoxemia as the area under the SpO2 desaturation curve near an apnoeic or hypopnoeic event. <bold>Aims and Objectives:</bold> We assessed whether HB is a better marker of the cardiovascular effects of OSA and continuous positive airway pressure (CPAP) treatment than usual OSA severity markers. <bold>Methods:</bold> In a post-hoc analysis of a CPAP withdrawal study on OSA patients (apnoea-hypopnoea-index (AHI)>10/h), randomised in a 1:1 ratio to two weeks of CPAP continuation or sham CPAP, we assessed the relationship between the treatment effect on HB (ΔHB) and the treatment effect on office morning blood pressure (BP), heart rate (HR), endothelial function (flow-mediated dilatation, FMD) and urinary catecholamines, comparing its CPAP response prediction capacity to models using other OSA markers. We calculated HB from raw polysomnography data with a Philips Respironics (USA) algorithm. <bold>Results:</bold> In 40 patients with OSA (age (SD) 63.1(5.8) y, oxygen desaturation index (ODI) at diagnosis 32(27)/h), HB and ODI increased after CPAP withdrawal compared to the control group by 80.0%min/h (95%CI 37.6-122.4) and 26.4/h (95%CI 16.3-36.5) (p<0.001). Controlling for baseline values and confounders, ΔHB was associated with change in urinary catecholamines and morning HR, but not in FMD, morning BP and nocturnal HR. Using a multivariate fractional polynomial regression model, ΔHB predicted the CPAP effect on catecholamines and morning HR better than AHI, ODI and t90. <bold>Conclusions:</bold> ΔHB in untreated OSA is associated with an increase in urinary catecholamines and morning HR and predicts their CPAP response better than other OSA markers.