Relationship between hypoxic burden and cardiovascular effects in OSA – a post hoc analysis of an RCT

ABSTRACT Objectives Hypoxic burden (HB) quantifies obstructive sleep apnoea (OSA)-associated nocturnal intermittent hypoxemia as the area under the peripheral desaturation curve near an apnoeic or hypopnoeic event. We assessed whether HB is a better marker of the cardiovascular effects of OSA than usual OSA severity markers. Methods In a continuous positive airway pressure (CPAP) withdrawal study in OSA patients (apnoea-hypopnoea-index (AHI) >10/h), randomized in a 1:1 ratio to two weeks of CPAP continuation or sham CPAP, the relationship between the treatment effect on HB (ΔHB) and the treatment effect on office morning blood pressure, heart rate (HR), endothelial function (flow-mediated dilatation, FMD), and urinary catecholamines was assessed using linear regression and multivariate fractional polynomial regression. The capacity of ΔHB in predicting CPAP response of these cardiovascular outcomes was compared with other OSA severity markers. Results In 40 patients with OSA (age 63.1±5.8y, AHI at diagnosis 37 (26-55)/h), AHI and HB significantly increased after CPAP withdrawal compared to the control group with 28 (19-62)/h and 37.8 (18.8-112.6) %min/h. Controlling for baseline values and confounders, ΔHB was associated with change in urinary catecholamines and morning HR, but not in FMD, morning blood pressure and nocturnal HR. Using a multivariate fractional polynomial regression model, ΔHB predicted the CPAP effect on catecholamines and morning HR better than AHI, oxygen desaturation index (ODI), time<90% SpO 2 , and arousal index. Conclusions HB in untreated OSA was associated with an increase in urinary catecholamines and morning HR and predicted their CPAP response better than other OSA severity markers. Trial registration Controlled-Trials.com , registration number ISRCTN 93153804.