Studies on clinical phenotypes/cluster analysis in patients with obstructive sleep apnoea (OSA)
| First author [ref.] | Methodology | Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7 | Group 8 |
| Joosten [86] | Clinical phenotypes of mild-to-moderate OSA + unsupervised K-means cluster analysis (n=1184, males 59.6%, single centre) No analysis of comorbidities | Phenotype: REM-predominant OSA (45.3%) Cluster 4 | Phenotype: non-REM predominant OSA (18.9%) No cluster identified | Phenotype: supine-predominant OSA (60.4%) Clusters 1 and 2 | Phenotype: intermittent OSA (12.7%) No cluster identified | Phenotype: isolated supine OSA (29.8%): as in group 3, but nonsupine AHI <5 Cluster 3 | Phenotype: isolated REM OSA: as in group 1, but non-REM AHI <5- No cluster identified | Phenotype: REM-supine overlap (20.5%) Clusters 5 and 6 | |
| Ye [87] | Latent class analysis in newly diagnosed moderate-to-severe OSA (n=822, males 81%, ISAC) Comorbidities: hypertension, diabetes, CVD, obstructive lung disease | Disturbed sleep: 32.7% of the sample (males 78.4%, mean age: 54.1 years); insomnia and other nocturnal symptoms, mean ESS 9.5% Comorbidities: hypertension 47.8%, diabetes 8.8%, CVD 14.4%, obstructive lung disease 21.3% | Minimally symptomatic: 24.7% of the sample (males 83.7%, mean age: 56.6 years); few mild symptoms, mean ESS 7.9% Comorbidities: hypertension 49.6%, diabetes 10.5%, CVD 18.3%, obstructive lung disease 16.2% | EDS: 42.6% of the sample (males 81.4%, mean age: 53.6 years); classic OSA presentation and sleepiness-related symptoms, mean ESS 15.7% Comorbidities: hypertension 41.6%, diabetes 7.5%, CVD 11.9%, obstructive lung disease 18.2% | |||||
| Vavougios [88] | Categorical PCA and two-step clustering in consecutive OSA patients (n=1472, males 83.9%, single centre) Charlson Comorbidity Index | Phenotype A: healthy, reporting sleep-related symptoms, moderate EDS, Cluster 3, 16.6% of the sample (males 65%, mean age 43.9 years, mean BMI 28 kg·m−2, mean ESS 6.7) Comorbidities: CHF 0.8%, CAD 2%, hypertension 20.5% | Phenotype B: mild OSA, few comorbidities Cluster 1, 19.6% of the sample (males 81%, mean age 48.2 years, mean BMI 29.2 kg·m−2, mean ESS 7.1) Comorbidities: CHF 0.3%, CAD 6.2%, hypertension 25.6% | Phenotype C1: moderate OSA, obesity, no comorbidities (males 85%, mean age 50.2 years, mean BMI 30.7 kg·m−2, mean ESS 8.5) Comorbidities: CAD 7.5%, hypertension 33.6%) | Phenotype C2: moderate OSA, obesity, severe comorbidities and stroke Cluster 2, 7.1% of the sample (males 80%, mean age 61.2 years, mean BMI 33.5 kg·m−2, mean ESS 9.1) Comorbidities: CHF 23.1%, CAD 33.7%, hypertension 73.1%, COPD 36.5%, stroke 31.7%, diabetes 44.2% | Phenotype D1: severe OSA, obesity, no comorbidities other than hypertension in 33.8% Cluster 4, 31.3% of the sample (males 94%, mean age 47.4 years, mean BMI 33.1 kg·m−2, mean ESS 10.3) Comorbidities: hypertension 33.8% | Phenotype D2: severe OSA, obesity, severe comorbidities, highest ESS and BMI Cluster 5, 10.0% of the sample (males 91%, mean age 58.8 years, mean BMI 35.6 kg·m−2, mean ESS 11.6) Comorbidities: CHF 40.5%, CAD 54.7%, hypertension 76.4%, COPD 23%, diabetes 29.1% | ||
| Saaresranta [89] | Four clinical presentations based on daytime–nocturnal symptoms (n=6555, males 75,4%, ESADA cohort) Comorbidities explored: cardiovascular metabolic, respiratory and psychiatric | EDS-no insomnia phenotype, 20.7% of the sample (males 77.2%, mean age 51.5 years, BMI >30 kg·m−2: 56.3%, mean ESS 14.9) Comorbidities: cardiovascular 48.9%, psychiatric 8.7% | EDS-insomnia phenotype, 23.7% of the sample (males 71.8%, mean age 52.2 years, BMI >30 kg·m−2: 61.4%, mean ESS 14.8) Comorbidities: cardiovascular 53%, psychiatric 14.5% | No EDS-no insomnia phenotype, 25.8% of the sample (males 83.0%, mean age 52.8 years, BMI >30 kg·m−2: 51.5%, mean ESS 6.1) Comorbidities: cardiovascular 52%, psychiatric 5% | No EDS-insomnia phenotype, 29.8% of the sample (males 70.4%, mean age 54.6 years, BMI >30 kg·m−2: 52.3%, mean ESS 6.0) Comorbidities: cardiovascular 56.8%, psychiatric 12.6% | ||||
| Bailly [90] | Ascending hierarchical cluster analysis in patients with moderate-to-severe OSA (n=18 263, males 72.8%, French OSA registry) Comorbidities explored: cardiovascular, metabolic and respiratory diseases | Young, overweight symptomatic OSA, few comorbidities (males 78.3%, mean age 48 years, mean BMI 29 kg·m−2, mean ESS: 10) Comorbidities: CAD 1%, arrhythmias 1.5%, CHF 0.6%, hypertension 13.9%, dyslipidaemia 10.7%, diabetes 2.4%, depression 12.6% Cluster 1, the young symptomatic (10% of the sample) | Elderly, minimally symptomatic obese OSA with few comorbidities (males 74.7%, mean age 63 years, mean BMI 31 kg·m−2, mean ESS: 12) Comorbidities: CAD 7%, arrhythmias 8.2%, CHF 2.8%, hypertension 48.8%, dyslipidaemia 22%, diabetes 9.7%, depression 7.7% Cluster 2, the older obese (23% of the sample) | Elderly, minimally symptomatic multimorbid OSA (males 66%, mean age 63 years, mean BMI 33 kg·m−2, mean ESS: 8) Comorbidities: CAD 20.5%, arrhythmias 8.2%, CHF 7.4%, hypertension 84.9%, dyslipidaemia 62.1%, diabetes 38.8%, depression 18% Cluster 3, the multidiseased old obese (18.4% of the sample) | Young, overweight minimally symptomatic OSA, no comorbidities (males 81.4%, mean age 49 years, mean BMI 28 kg·m−2, mean ESS: 10) Comorbidities: CAD 0.6%, arrhythmias 0.8%, CHF 0.4%, hypertension 4.2%, dyslipidaemia 3.8%, diabetes 0.3%, depression 5.2% Cluster 4, the young snorer (14.9% of the sample) | Middle-aged, few OSA symptoms and few comorbidities (males 69.3%, mean age 56 years, mean BMI 31 kg·m−2, mean ESS: 11) Comorbidities: CAD 2.9%, arrhythmias 04%, CHF 1.5%, hypertension 34.3%, dyslipidaemia 23.8%, diabetes 6.3%, depression 16.2% Cluster 5, the drowsy obese (19.2% of the sample) | Middle aged, symptomatic multimorbid OSA, poor lifestyle habits (males 72.3%, mean age 60 years, mean BMI 33 kg·m−2, mean ESS: 11) Comorbidities: CAD 12.4%, arrhythmias 12.9%, CHF 3.7%, hypertension 75.1%, dyslipidaemia 53.3%, diabetes 26.4%, depression 26.4% Cluster 6, the multidiseased obese symptomatic (14.5% of the sample) | ||
| Lacedonia [91] | PCA in consecutive patients with moderate-to-severe OSA (n=198, males 81%, single centre) | Young, severely obese patients, with severe OSA, nocturnal hypoxaemia and high prevalence of comorbidities (50% of the sample, males 77%) | Patients with moderate-to-severe OSA and low risk of nocturnal hypoxaemia (41.4% of the sample, males 85%) | Older patients, overweight or mildly obese, with severe OSA and low nocturnal hypoxaemia or ESS (8.6% of the sample, males 82%) | |||||
| Mihaicuta [92] | Cluster analysis on consecutive OSA patients (n=1371) and non-OSA controls (n=611), single centre Single and combined cardiovascular, respiratory and nutritional comorbidities | Phenotype 1: 21.4% of total sample: severe OSA, obese males, thick neck, hypertension, age 40–60 years, with cardiovascular, nutritional and respiratory comorbidities overlap | Phenotype 2: 8.5% of total sample: moderate-to-severe OSA, obese females, thick neck, hypertension, age 40–60 years, with overlap of cardiovascular and nutritional comorbidities | Phenotype 3: 13.0% of total sample: moderate-to-severe OSA (less severe than other phenotypes), obese females, thin neck, hypertension, age 40–60 years, overlap of CV and nutritional comorbidities, no single respiratory comorbidity | Phenotype 4: 15.2% of total sample: mostly severe OSA, obese males, thick neck, hypertension, age >60 years, with comorbidities (single respiratory comorbidity rare) | Phenotype 5: 5.5% of total sample: variable OSA severity, obese young (20–40 years) males, thick neck, normotension, no EDS, nutritional comorbidities alone or overlapping | Phenotype 6: 4.4% of total sample: moderate-to-severe OSA, obese males, thick neck, normotension, no EDS, nutritional comorbidities | Phenotype 7: 15.8% of total sample: moderate-to-severe OSA (less severe than other phenotypes), males of all ages, thin neck, normotension, no EDS, no comorbidity or single respiratory comorbidity | Phenotype 8: 15.9% of total sample: variable OSA severity, males of all ages, thin neck, no EDS, hypertension, most often single cardiovascular comorbidity |
| Gagnadoux [93] | Latent class analysis in moderate-to-severe OSA (n=5983, 71.1% males), multicentre prospective sleep cohort; CPAP compliance (n=3090) Comorbidities: cardiovascular, hypertension, diabetes CPAP success defined as use at 6 months ≥4 h·night-1 + ESS decrease by ≥4 points in patients with baseline ESS ≥11 or increase of 7 points in energy/vitality score | Female predominance (90.2%), age >65 years: 42.6%, insomnia complaints (40.5%), depressive symptoms (39.6%), obesity (84.7%) and associated comorbidities (hypertension: 64.3%; cardiovascular: 13.4%; diabetes 31.5%) CPAP use ≥4 h·night-1 80.5%, CPAP success 37.8% Cluster 1, female OSA (14.2%) | Male predominance (92.3%), age >65 years: 59.0%, marked nocturnal OSA symptoms, EDS (66.3%), obesity (65.2%), insomnia (13%), depressive symptoms (41.2%) Comorbidities: hypertension: 79.6%, cardiovascular 53.8%; diabetes 38.5% CPAP use≥4 h·night-1 80.7%, CPAP success 54.1% Cluster 2, male severe OSA with comorbidities (15.1%) | Male predominance (61.7%), age >65 years: 3.6%, marked nocturnal OSA symptoms, EDS (97.6%), obesity (53.6%), insomnia (2.9%), depressive symptoms (34.5%) Comorbidities: hypertension 13.0%, cardiovascular: 3.6, diabetes 4.2% CPAP use ≥4 h·night-1 75.8%, CPAP success 57.6% Cluster 3, severe OSA (18.2%) | Male predominance (83.4%), age >65 years: 19.8%, nocturnal OSA symptoms, obesity (30.3%), insomnia complaints (32.4%), depressive symptoms (7.2%) low prevalence of EDS (29.5%) or comorbidities (hypertension: 6.3%; cardiovascular: 3.5%; diabetes 0%) CPAP use ≥4 h·night-1 79.5%, CPAP success 39% Cluster 4, mildly symptomatic OSA (32%) | Male predominance (87.0%), age >65 years: 66.7%, low frequency of nocturnal OSA symptoms, obesity (64.4%), insomnia complaints (21.5%), depressive symptoms (2.2%) low prevalence of EDS (16.4%), high prevalence of comorbidities (hypertension: 74.8%, cardiovascular 37.6%, diabetes 31%) CPAP use ≥4 h·night-1 85.5%, CPAP success 25.7% Cluster 5, comorbid OSA (20.5%) | |||
| Babbin [94] | Time-series analysis followed by dynamic cluster analysis to identify patterns of CPAP use over 6 months (n=161, OSA features or comorbidities not specified), single centre | Great CPAP users (17.2%): mean use 7.3 h·night-1, no slope over time | Good CPAP users (32.8%): mean use 5.7 h·night-1, no slope over time | Low users (22.7%): mean use 2.3 h·night-1, decreasing slope over time (−0.013 h·night-1) | Slow decliners (27.3%): mean use 4.3 h·night-1, decreasing slope over time (−0.007 h·night-1) |
REM: rapid eye movement; AHI: apnoea/hypopnoea index; ISAC: Icelandic Sleep Apnoea Cohort; CVD: cardiovascular disease; ESS: Epworth Sleepiness Scale; EDS: excessive daytime sleepiness (i.e. ESS ≥10); PCA: principal component analysis; BMI: body mass index; CHF: chronic heart failure; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; ESADA: European Sleep Apnea Database.