Neurology. 2026 Aug 11;107(3):e218334. doi: 10.1212/WNL.0000000000218334. Epub 2026 Jul 21.
ABSTRACT
BACKGROUND AND OBJECTIVES: Obesity is a key risk factor underlying both obstructive sleep apnea (OSA) and cardiovascular disease (CVD). The objective of this study was to determine differential strength of associations of adiposity indices with recurrent CVD events in patients with established CVD and OSA.
METHODS: Post hoc analyses of the international Sleep Apnea Cardiovascular Endpoints (SAVE) trial where participants with moderate-to-severe OSA and established CVD were randomized to usual care plus continuous positive airway pressure (CPAP) treatment or usual care alone. Cox proportional hazards models were used to evaluate associations of body-mass index (BMI) and waist-to-height ratio (WHtR), with the risk of composite CVD events.
RESULTS: Of 2,662 participants with OSA with established CVD, 846 (31.8%) were obese by BMI (≥30 kg/m2), while 2,544 (95.6%) had central adiposity (WHtR ≥0.50). Over a 3.7-year follow-up, conventional BMI categories were not clearly associated with composite CVD events, although spline analyses suggested potential nonlinear associations. In contrast, WHtR showed a clear overall association with composite CVD events (p for overall = 0.0187). In quartile analyses, participants in the highest WHtR quartile had a 1.52-fold higher risk of composite CVD events than those in the lowest quartile (hazard ratio 1.52, 95% CI 1.12-2.05). There was no heterogeneity in the effect of CPAP treatment on composite CVD events or CPAP adherence by any baseline adiposity measures.
DISCUSSION: In this large trial of adults with co-occurring OSA and CVD, nearly all had central adiposity (as assessed by WHtR), which showed a more consistent association with the risk of future CVD events. In contrast, the relationship between BMI and CVD outcomes appeared more complex, suggesting that conventional BMI categories may not adequately capture cardiovascular risk in this population.
TRIAL REGISTRATION INFORMATION: The SAVE trial is registered at ClinicalTrials.gov (Unique identifier: NCT00738179).
PMID:42479992 | DOI:10.1212/WNL.0000000000218334