Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients

Abstract

BackgroundClinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established.MethodsA prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ≥5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness (“EDS”) and nocturnal sleep problems other than OSA (labelled as “insomnia”): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype.ResultsThe EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0±25.5/h vs. 27.9±22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188–1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity.ConclusionsPhenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS.

Personalised medicine in sleep respiratory disorders: focus on obstructive sleep apnoea diagnosis and treatment

“…The European Sleep Apnea Database (ESADA) study analysed similar OSA phenotypes, i.e. a combination of diurnal and nocturnal symptoms, in a multicentre large cohort [89]. Results were similar to those of YE et al [87] and coworkers, with an additional finding of a high prevalence of psychiatric comorbidities, especially in OSA patients reporting symptoms of insomnia.…”

“…Variability in results can be expected, since the studies differed in the variables entered in the analyses. In addition, the studies are heterogeneous in the number of patients included, and only three studies were multicentric [89,90,93]. Finally, the complexity of OSA can affect the results.…”

Co-Morbid Insomnia and Sleep Apnea (COMISA): Prevalence, Consequences, Methodological Considerations, and Recent Randomized Controlled Trials

“…For example, OSA has historically been conceptualized as a disorder impacting middle-aged and older-adult males, who are overweight or obese and present with complaints of excessive daytime sleepiness, tiredness, sedation, and snoring. Although epidemiological studies provide statistical support for these 'risk factors' (e.g., OSA is associated with male gender, increased age, overweight and obesity, snoring, and daytime sleepiness [14]), reliance on this single profile clearly does not represent all OSA sufferers [26][27][28]. Alternatively, insomnia has historically been conceptualized as a disorder primarily impacting middle-aged and older-adult females who are predisposed to anxiety, stress, and cycles of cognitive rumination.…”

“…[40]. Between 2013 and 2018, a number of large cluster analyses of OSA samples also identified that 32%-54% of OSA patients indicate symptoms of 'disturbed sleep', characterized by nocturnal insomnia symptoms, more frequent use of sedative-hypnotic medications, and lower use of CPAP therapy [26,27,41,42]. Most recently, Zhang and colleagues conducted a systematic review and meta-analysis including 37 studies investigating the co-morbidity of insomnia and OSA, and reported that 35% of insomnia patients have an AHI of ≥5, and 29% have an AHI of ≥15, while 38% of OSA patients meet insomnia criteria [43].…”

The ageing brain in sleep apnoea: paradoxical resilience, survival of the fittest, or simply comparing apples and oranges?

“…Over the last several decades, we have witnessed substantial increases in the granularity of the morbid phenotype of OSA, and such observations have prompted us to rethink some of the stricter early concepts. Among them, rather than viewing OSA as a single disease model that is applicable to all patients, we have formulated the conceptual framework of distinct phenotypes of OSA that may be driven by different mechanisms, link to different clinical manifestations, and display divergent responses to therapy [1][2][3][4][5][6]. In this contextual setting, the aspirational goals of the field are to first and foremost identify those OSA patients likely to benefit from treatment and administer the correct intervention, i.e.…”