Abstract
Background: The apnea–hypopnea index (AHI) is the conventional metric for grading obstructive sleep apnea (OSA) severity; however, it poorly reflects the true physiological impact of the disorder. The recently introduced hypoxic burden (HB) quantifies total exposure to intermittent hypoxia by integrating the duration and depth of oxygen desaturations associated with respiratory events. HB has emerged as a more biologically relevant and prognostically powerful biomarker than AHI. Methods: This narrative review summarizes the concept, methodology, and clinical significance of HB. Theoretical foundations, algorithmic approaches, and standardization challenges are discussed, along with evidence from major cohort studies evaluating the relationship between HB, cardiovascular outcomes, and treatment response. Results: HB integrates frequency, duration, and amplitude of desaturations into a continuous measure of nocturnal hypoxemia. Multiple independent cohorts (e.g., MrOS, Sleep Heart Health Study) have demonstrated that HB predicts cardiovascular morbidity and mortality more strongly than AHI. Elevated HB is associated with oxidative stress, endothelial dysfunction, sympathetic activation, and systemic inflammation. Reductions in HB during therapy with continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or oxygen supplementation correlate with improvements in hemodynamic and inflammatory markers, suggesting its potential as a dynamic therapeutic target. Conclusions: HB represents a major advance in the physiological assessment of OSA, linking sleep-related hypoxemia to biological stress and clinical outcomes. Its clinical integration—through standardized computation and incorporation into digital and AI-driven platforms—may enable personalized, physiology-based sleep medicine and establish HB as a key prognostic and therapeutic biomarker comparable to HbA1c in diabetes.