Phenogroup-Based Stratification of Cardiovascular Risk in Obstructive Sleep Apnea

Background Obstructive sleep apnea (OSA) exhibits substantial phenotypic heterogeneity, but its prognostic relevance in patients with coronary artery disease (CAD) undergoing revascularization remains uncertain. Methods We pooled data from two prospective cohorts of CAD patients undergoing percutaneous coronary intervention or coronary artery bypass grafting (n=2318). Major adverse cardiac and cerebrovascular events (MACCE; cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization) were assessed over a mean follow-up of 1.9±1.1 years. Latent class analysis using nine clinical variables identified phenogroups. Associations between OSA (apnea–hypopnea index ≥15) and MACCE were evaluated using Cox regression. Results Three phenogroups were identified: (1) Younger-Sleepy-Hypoxia (42.2%), (2) Cardiorenal-Metabolic (30.9%), and (3) Old-Lean-Chinese (26.9%). OSA prevalence was similar across groups (45.5%, 50.7%, and 47.8%). The overall incidence of MACCE was 11.4% and did not differ significantly across phenogroups (p=0.127). OSA was associated with increased MACCE risk in the overall cohort (adjusted HR 1.55, 95% CI 1.20–2.00; p<0.001). In phenogroup analyses, this association was significant in phenogroup 1 (adjusted HR 1.57, 95% CI 1.04–2.36; p=0.030), borderline in phenogroup 2 (adjusted HR 1.55, 95% CI 0.98–2.43; p=0.059), and not significant in phenogroup 3 (adjusted HR 1.32, 95% CI 0.81–2.16; p=0.263). Conclusions In revascularized CAD patients, OSA was associated with increased cardiovascular risk in the overall cohort, with heterogeneity across phenogroups. These findings support phenogroup-based risk stratification, pending external validation.