Continuous positive airway pressure but not Liraglutide-mediated weight loss improves early cardiovascular disease in obstructive sleep apnea: Data from a randomized proof-of-concept study

Abstract Background Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) therapy is uncertain. However, most randomized-controlled trials have focused on the role of CPAP in secondary prevention although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it to a glucagon-like-peptide (GLP)-1-mediated weight loss regimen in OSA. Methods We performed a randomized proof-of-concept study (clinicaltrials.gov: NCT04186494 ) comparing CPAP, a liraglutide-based weight loss regimen (Lir) alone or both in combination for 24 weeks in 30 non-diabetic patients with moderate to severe OSA (50±7 years, 80% males, apnea-hypopnea index [AHI] 50±19/hr, body mass index [BMI] 35.0 ±3 kg/m 2 ). Baseline characteristics were similar between groups. Beside extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluorodeoxyglucose (FDG)-PET-CT for measurement of aortic wall inflammation (target-to-background ratio [TBR]) and coronary CT angiography (CCTA) for semi- automated coronary plaque analysis. Results CPAP alone and combination resulted in greater reduction in AHI than Lir alone at 24 weeks (mean difference -45/hr and -43/hr, respectively, vs -12/hr, p<0.05). Both Lir and combination led to significant weight loss of 6±3% and 4±4%, respectively. Despite CPAP resulting in small weight gain, only the CPAP alone group demonstrated a significant decrease in vascular inflammation (aortic wall TBR from 2.03±0.34 to 1.84±0.43, p 0.010) associated with improvement in endothelial function and decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as marker of unstable plaque also decreased with CPAP (from 571±490 to 334±185mm 3 ) and with combination therapy (from 401±145 to 278±126mm 3 ) but not with Lir. Conclusion These data suggest that CPAP therapy, but not GLP-1 mediated weight loss, improves vascular inflammation and reduces low-attenuation coronary artery plaque volume in OSA patients. These novel findings support the benefit of CPAP therapy in modifying early CV disease. Clinical Perspective What is new? This is the first study comparing standard CPAP therapy to a GLP-1 mediated weight loss regimen in obstructive sleep apnea (OSA). The study utilized 18F-FDG PET CT and artificial intelligence-enabled coronary CT quantification of coronary artery plaque subtypes to determine treatment effects on early atherosclerotic disease processes. What are the clinical implications? CPAP in contrast to GLP-1-mediated weight loss may improve early atherosclerotic and potentially modifiable disease processes in obstructive sleep apnea (OSA). These data support the benefit of CPAP in the primary prevention of cardiovascular diseases in OSA.