Cluster-derived obstructive sleep apnea phenotypes and outcomes at 5-year follow-up

Abstract

Study objectives: Obstructive sleep apnea (OSA) is a heterogeneous, complex disease. We aimed to identify OSA phenotypes through cluster analysis and to perform a long-term follow-up to validate the phenotypes.

Methods: We applied a partitioning around medioids technique in a cohort of 1,217 participants recently diagnosed with OSA. We performed a 5-year follow-up analyzing the incidence of comorbidities, chronic medication, hospital admissions, mortality, and the influence of continuous positive airway pressure treatment on mortality risk.

Results: We identified three phenotypes: two predominantly male clusters, one composed of middle-aged participants with overweight, moderate OSA, and cardiovascular risk factors and the other consisting of older, obese participants with severe OSA, cardiovascular risk factors, ischemic heart disease (18.4%), and atrial fibrillation (9.7%). The third cluster was composed of 77% female participants with moderate OSA; cardiovascular risk factors; the highest prevalence of depression (15.7%); and high prescription of antidepressants (55.1%), anxiolytics (40.0%), hypnotics, sedatives (11.1%), nonsteroidal anti-inflammatory drugs (67.9%), and weak opioids (15.1%). The baseline characteristics of each cluster maintained the same trend over time regarding the incidence of new comorbidities, medication intake, hospitalization rates, and reasons for admission. The absence of continuous positive airway pressure treatment was associated with a significantly higher risk of all-cause mortality (hazard ratio 5.84, confidence interval 2.9-11.8), especially in the older men (hazard ratio 7.7, confidence interval 4.06-14.63) and predominantly female clusters (hazard ratio 2.79, confidence interval 1.34-5.79).

Conclusions: We identified three phenotypes with relevant clinical and prognostic implications in order to improve personalized strategies in OSA management.

Citation: Silveira MG, Sampol G, Mota-Foix M, Ferrer J, Lloberes P. Cluster-derived obstructive sleep apnea phenotypes and outcomes at 5-year follow-up. J Clin Sleep Med. 2022;18(2):597-607.

Keywords: CPAP; OSA; comorbidities; phenotypes.