Real-World Generalizability of Sleep Apnea Related Polysomnographic Metrics and Their Associations with Clinical...

Advanced polysomnographic (PSG) metrics reflecting the physiological causes and consequences of sleep apnea may enable precision medicine in research settings, but their feasibility in routine clinical practice has yet to be demonstrated.

Assess (1) the generalizability of PSG metrics from research to clinical cohort, and (2) their associations with a broad range of comorbid diseases, many of which have not been previously examined.

PSG metrics including endotypes (eg, loop gain) and physiological burdens (eg, hypoxic burden) were estimated from diagnostic polysomnographs of 6,427 participants at Mass General Brigham (MGB; Boston, MA). Comorbid conditions analyzed from MGB's medical record system included 9 representative cardio-metabolic and respiratory diseases, as well as 408 prevalent diseases. Associations were assessed using modified Poisson and LASSO regression.

The sample included 62% females, age: 52.9 ± 16.8 years, and apnea-hypopnea index (AHI) 21.4 ± 15.9 events/hr. Associations between endotypes and demographics/obesity-related factors were consistent with prior observational studies (median difference in β = 0.03SD). After adjusting for AHI, older age was associated with lower heart rate (-0.40SD) and arousal burdens (-0.23SD), while higher BMI was associated with increased hypoxic burden (0.25SD). Having demonstrated that there is reasonable concordance with published data, our subsequent analysis identified distinct and clinically meaningful associations between advanced PSG metrics and comorbid conditions. Specifically, elevated loop gain, ventilatory burden, and hypoxic burden were associated with hypertension, diabetes, and renal failure; increased ventilatory instability was associated with cardiovascular disease; and reduced collapsibility and ventilatory instability with chronic airway obstruction. Even after LASSO-based selection, no single PSG metric consistently predicted risk across all comorbidities; ventilatory instability showed the most associations among endotypic traits, and heart rate burden among physiological burdens, underscoring the heterogeneity of OSA pathophysiology.

Phenome-wide analyses of a large clinical cohort demonstrate the real-world feasibility and clinical relevance of extracting advanced PSG metrics, supporting their potential to identify personalized, mechanism-specific intervention targets for sleep apnea.