Effects of CPAP on OSA-related cardiovascular risk markers: a two-week CPAP withdrawal and re-initiation study

BackgroundThe cardiovascular (CV) benefit of CPAP in OSA remains debated and its effects on new OSA-related CV risk markers are unclear. We aimed to quantify short-term CPAP effects on these markers along with vascular and autonomic phenotypes. MethodsIn a 2-week withdrawal study, patients on long-standing effective CPAP took part in three visits (V1-V3: on/off/back-on CPAP) with overnight polygraphy followed by vascular and autonomic phenotyping. Co-primary endpoints included endothelial function assessed by flow-mediated dilation (FMD) and baroreflex sensitivity (BRS), hypoxic burden (HB), pulse wave amplitude drop index (PWADi) and spontaneous-PWADi (excl. apnoea-triggered drops), and event-related heart-rate response ({Delta}HR). Between-visit differences were tested in adjusted mixed models, with visit or within-participant changes in AHI/HB as fixed effects. ResultsIn 42 participants (61{+/-}10 years, 83% male), CPAP withdrawal reinstated OSA (medians [IQR] V1 to V3: AHI 3.9[1.5, 8.8] to 33.4[19.5, 42.1] to 4.0[2.0, 8.8] events/h, HB 4.3[1.1, 8.7] to 51.3[19.7, 83.7] to 2.0[1.2, 6.5] %{middle dot}min/h, p<0.001) and increased total PWADi (mean{+/-}SD 42.25{+/-}18.73 to 50.22{+/-}17.77 to 41.29{+/-}17.14 drops/h, p<0.001), while spontaneous PWADi decreased as respiratory-events recurred (-1.17 drops/h per 10 events/h, p=0.015) along with FMD (3.7{+/-}1.9% to 3.2{+/-}2.5% to 4.2{+/-}2.7%, V2 vs V3 p=0.047). {Delta}HR and BRS were stable across visits. ConclusionShort-term CPAP re-initiation improved endothelial function (FMD), with no significant effects on autonomic measures (BRS, {Delta}HR) or structural vascular indices. This supports a temporal dissociation between rapidly reversible exposure metrics (AHI, HB) and slower dynamics of autonomic markers. Changes in spontaneous PWADi suggests that it may track physiological CPAP benefits beyond indices driven primarily by respiratory-event frequency.