Obstructive Sleep Apnea Phenotypes and Markers of Vascular Disease: A Review

Abstract

Obstructive sleep apnea (OSA) is a chronic and heterogeneous disorder that leads to early mortality, stroke, and cardiovascular disease (CVD). OSA is defined by the apnea–hypopnea index, which is an index of OSA severity that combines apneas (pauses in breathing) and hypopneas (partial obstructions in breathing) associated with hypoxemia. Yet, other sleep metrics (i.e., oxygen nadir, arousal frequency), along with clinical symptoms and molecular markers could be better predictors of stroke and CVD outcomes in OSA. The recent focus on personalized medical care introduces the possibility of a unique approach to the treatment of OSA based on its phenotypes, defined by pathophysiological mechanisms and/or clinical presentation. We summarized what is known about OSA and its phenotypes, and review the literature on factors or intermediate markers that could increase stroke risk and CVD in patients with OSA. The OSA phenotypes where divided across three different domains (1) clinical symptoms (i.e., daytime sleepiness), (2) genetic/molecular markers, and (3) experimental data-driven approach (e.g., cluster analysis). Finally, we further highlight gaps in the literature framing a research agenda.

Clinical Features and Contributing Factors of Excessive Daytime Sleepiness in Chinese Obstructive Sleep Apnea Patients: The Role of Comorbid Symptoms and Polysomnographic Variables

“…Different phenotypes have been increasingly identified in OSA and may promote precise medicine. Daytime sleepiness has become a primary criterion for symptom-based OSA classification [12]. In-depth studies of the features and differences of OSA patients with or without EDS may help improve the screening, diagnosis, and prognosis of OSA in the future.…”

Sleep and Stroke: New Updates on Epidemiology, Pathophysiology, Assessment, and Treatment

“…Evaluation of SDB phenotypes represents a novel strategy to risk stratify and personalize preventive and therapeutic strategies for stroke. (15) Stroke Perspective-In the inpatient acute stroke setting, aggressive risk factor control and identification of stroke etiology are immediately initiated. However, comorbidities such as SDB have largely been neglected.…”

“…(13, 14) Studies using a priori definitions of sleep phenotypes described vascular risk among SDB patients with sleepiness. (15) Interestingly, data-driven methods using advanced statistical analyses suggest a heterogeneity of clinical phenotypes associated with increased stroke and vascular risk. (15)(16)(17)(18)(19)(20) For example, the Icelandic Sleep Apnea Cohort (n = 822) of patients with AHI ≥ 15 described three different SDB phenotypes based on cluster analysis.…”

Do symptoms of sleepiness and insomnia in US veterans with obstructive sleep apnea vary by age?

“…Aging can influence the evaluation of OSA including reports of subjective daytime sleepiness and comorbid insomnia symptoms [4]. For example, the Epworth sleepiness scale (ESS), one of the most common screening instruments for assessing sleepiness, may be limited among older individuals as they may not perform all of the queried daytime activities [5].…”