Beyond the apnea-hypopnea index: clinical phenotypic heterogeneity of obstructive sleep apnea in an Indian tertiary referral cohort using level III polysomnography

Obstructive sleep apnea (OSA) is usually classified by a single severity index, the Apnea-Hypopnea Index (AHI), which does not capture the clinical heterogeneity described in other populations. To characterize clinically distinct OSA phenotypes by body habitus, symptom-severity relationship, and by respiratory event type in an Indian tertiary referral cohort, using level III polysomnography. Retrospective analysis of 309 patients with OSA (AHI≥5) from consecutive level III polysomnography studies at a tertiary Indian center. Phenotypes were defined as follows: 1) lean [body mass index (BMI)<25 kg/m²] versus non-lean OSA; 2) symptomatic vs. asymptomatic disease, using an Epworth Sleepiness Scale (ESS) score of 10 as a threshold, crossed with AHI severity; 3) apnea-predominant vs. hypopnea-predominant disease, from the respective event indices. An exploratory unsupervised cluster analysis on physiological variables was performed as a comparator. A lean phenotype was present in 12.3% of patients (95% confidence interval 9.1-16.5) and had lower AHI, less hypoxemia, and fewer daytime symptoms than non-lean OSA, with less moderate-to-severe disease (40.5% vs. 68.4%, p=0.002). Symptom burden was poorly matched to severity: 52.7% of severe OSA patients were not sleepy (ESS<10), while 21.5% of mild OSA patients were. Sleepy patients had a greater hypoxemic burden but similar body habitus. Apnea-predominant disease (54.3% of patients with usable indices) occurred in younger, leaner patients but with a higher AHI than hypopnea-predominant disease. Both the lean-phenotype association with less severe disease and the apnea-predominant AHI difference persisted after adjustment for age, sex, and BMI. STOP-Bang score did not reliably discriminate moderate-to-severe disease in this already high-risk referral population (AUC 0.56), and hypertension and diabetes prevalence did not differ between lean and non-lean phenotypes. ODI graded on AHI's own thresholds agreed with the AHI category in 67.4% of patients (quadratic-weighted κ 0.82) and identified moderate-to-severe disease with 89% sensitivity and 92% specificity. Unsupervised clustering on AHI-correlated physiological variables did not identify phenotypes independent of severity. OSA in this referral cohort separates into body-habitus, symptom-discordance and event-type phenotypes that are not interchangeable with AHI severity alone. Recognizing these patterns may help identify lean patients, underrecognized asymptomatic severe disease, and mechanistically distinct event patterns.