Heterogeneity of Vascular Inflammation in Obstructive Sleep Apnea: Effects of CPAP Therapy

Abstract Rationale There is a critical gap in our understanding of how treatment with continuous positive airway pressure (CPAP) modulates vascular inflammation in patients with obstructive sleep apnea (OSA). We have shown that the effects of CPAP treatment on cardiovascular outcomes in OSA vary between individuals (heterogeneity of treatment effects HTE). In this study, we evaluate HTE on vascular inflammation in OSA patients undergoing CPAP therapy. Methods We recruited adults with moderate-to-severe OSA (respiratory disturbance index, RDI ≥15) who underwent 18F-FDG Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) at baseline and after 3 months of CPAP. We measured vascular inflammation in the carotid arteries and aorta, using standardized uptake values (SUV). Carotid SUVmax was the primary outcome. We used multivariable linear regression and linear mixed-effects models to evaluate associations between OSA metrics and vascular inflammation at baseline, and after CPAP. We explored HTE using k-means clustering to identify distinct clusters based on changes in carotid vascular inflammation after CPAP treatment. Results 180 patients completed baseline imaging, and 135 returned for follow-up. OSA severity and hypoxic burden were significantly associated with vascular inflammation, though this association was attenuated after adjusting for cardiovascular risk factors. There were no significant changes in vascular inflammation after CPAP. However, significant HTE was observed, with three distinct clusters of patients: those showing a decrease in carotid vascular inflammation (-16.6% CI -19.8%,-13.3%), an increase (+24.2% CI 19.3%, 29.2%), or no significant change (-1.18% CI -3.7%, 1.4%) in inflammation post-CPAP. Patients with no change or an increase in vascular inflammation post-CPAP were more likely to have a history of smoking (P = 0.009) and a higher baseline delta heart rate (P = 0.012) compared to those with a decrease in vascular inflammation post-CPAP. Conclusion Although CPAP therapy did not uniformly reduce vascular inflammation in OSA patients, there was substantial heterogeneity in treatment responses across participant clusters. Differences in baseline lifestyle and polysomnographic features between these clusters may provide insight into factors driving variability in subclinical cardiovascular disease and treatment outcomes in OSA.