Patient characteristics
The cluster analysis identified four clusters. Compared to Clusters 1 and 2, Cluster 3 and 4 were younger, had a higher male:female ratio, a higher BMI and history of smoking. The ESS scores were elevated in Cluster 3 compared to other clusters (Table 1).
Table 1
Summary of the main features in the identified clusters
| All Clusters (n = 97) | Cluster 1 (n = 49) | Cluster 2 (n = 6) | Cluster 3 (n = 11) | Cluster 4 (n = 31) | P-value |
Age | 56 ± 13 | 57 ± 11 | 65 ± 13 | 52 ± 15 | 51 ± 12 | < 0.0001 |
Sex (male) % | 80 | 86 | 90 | 60 | 75 | 0.462 |
Body weight, kg | 81 ± 1.7 | 73 ± 11 | 78 ± 17 | 94 ± 18 | 93 ± 15 | 0.0001 |
Body mass index, kg/m2 | 29 ± 5.1 | 26 ± 2.6 | 28 ± 5.8 | 34 ± 6.7 | 33 ± 3.5 | < 0.0001 |
Have never smoked % | 16 | 38 ± 28 | 20 ± 31 | 40 ± 41 | 56 ± 16 | 0.562 |
ESS score | 8.7 ± 4.8 | 8.7 ± 4.8 | 7.3 ± 3.6 | 9.4 ± 4.8 | 8.7 ± 5.3 | 0.74 |
All data are expressed as mean + SD values. |
The P-values are derived by ANOVA with Turkey’s post hoc tests. |
ESS: Epworth Sleepiness Scale |
The 97 OSA patients had a mean age of 56.0 years (22 to 82 years) and 80% were men, around 16% were current smokers, and the mean ESS score was 8.7. Of the identified clusters, Clusters 3 and 4 exhibited high leptin levels. The leptin/adiponectin ratio was high in Cluster 3, despite a similar BMI in Clusters 3 and 4. Cluster 2 exhibited high adiponectin levels.
Table 2 shows the PSG results. Of the enrolled OSA patients, 17 (18%) had moderate (AHI 20–30/h), 45 (46%) severe (AHI 30–60/h), and 35 (36%) most severe (AHI ≥ 60) OSA, with a mean AHI of 57/h. The data related to sleep-disordered breathing (obstructive apnea, apnea index, AHI, oxygen desaturation index 3%, mean SpO2, and arousal index) were worse in Cluster 3, followed by Cluster 4.
Table 2
| All Cluster (n = 97) | Cluster 1 (n = 49) | Cluster 2 (n = 6) | Cluster 3 (n = 11) | Cluster 4 (n = 31) | P Value |
Wake time (%) | 14 ± 10 | 13 ± 10 | 22 ± 14 | 14 ± 7.5 | 12 ± 8.3 | 0.952 |
NREM1 (%) | 47 ± 19 | 40 ± 15 | 67 ± 22 | 56 ± 19 | 49 ± 20 | 0.968 |
NREM2 (%) | 37 ± 15 | 42 ± 13 | 25 ± 18 | 28 ± 17 | 35 ± 14 | 0.67 |
NREM3 (%) | 3.0 ± 4.5 | 2.9 ± 3.9 | 0.2 ± 0.7 | 3.5 ± 5.5 | 3.8 ± 5.5 | 0.503 |
REM (%) | 13 ± 6.3 | 14 ± 5.7 | 11.7 ± 11.7 | 12 ± 4.8 | 12 ± 5.8 | 0.128 |
AHI (/hr) | 57 ± 68 | 40 ± 15 | 60 ± 20 | 72 ± 25 | 84 ± 30 | < 0.0001 |
CA (/hr) | 0.7 ± 2.3 | 0.5 ± 1.2 | 2.7 ± 6.7 | 0.9 ± 2.6 | 0.3 ± 0.7 | 0.31 |
OA (/hr) | 23 ± 20 | 17 ± 15 | 37 ± 31 | 37 ± 26 | 27 ± 20 | 0.01 |
MA (/hr) | 3.7 ± 8.8 | 1.9 ± 3.7 | 13 ± 21 | 2.2 ± 5.1 | 5.4 ± 10 | 0.01 |
Apnea (/hr) | 32 ± 43 | 20 ± 16 | 55 ± 26 | 42 ± 27 | 46 ± 75 | 0.113 |
Hypopnea (%) | 23 ± 14 | 20 ± 9 | 11 ± 12 | 29 ± 21 | 29 ± 17 | 0.471 |
Mean SpO2 (%) | 94 ± 2.6 | 95 ± 1.8 | 94 ± 3.0 | 92 ± 3.4 | 93 ± 2.9 | 0.321 |
Lowest SpO2 (%) | 72 ± 13 | 76 ± 11 | 67 ± 14 | 62 ± 3 | 68 ± 12 | 0.458 |
SpO2 > 90% (%) | 9.7 ± 14 | 5.0 ± 9.4 | 13 ± 16 | 18 ± 19 | 15 ± 17 | < 0.0001 |
SpO2 > 85% (%) | 4.9 ± 9.7 | 2.4 ± 6.4 | 6.7 ± 12 | 10 ± 14 | 7.5 ± 11 | < 0.0001 |
Arousal (/hr) | 54 ± 20 | 46 ± 14 | 74 ± 19 | 68 ± 29 | 60 ± 20 | < 0.0001 |
All data are expressed as mean + SD values. |
The P-values are derived by ANOVA with Turkey’s post hoc tests. |
NREM: Non Rapid Eye Movement; REM: Rapid Eye Movement; AHI: Apnea-Hypopnea Index; CA: Central apnea; OA: Obstructive apnea; MA: Mixed Apnea; SpO2: peripheral capillary oxygen saturation |
Table 3 shows the lung function test results. Although no ventilatory dysfunction was observed, forced vital capacity and forced expiratory volume were lower in Clusters 2 and 3. There were no significant differences regarding peripheral airway obstruction.
Table 3
| All Clusters (n = 97) | Cluster 1 (n = 49) | Cluster 2 (n = 6) | Cluster 3 (n = 11) | Cluster 4 (n = 31) | P-value |
VC (%) | 112.8 ± 15.7 | 100 ± 16 | 100 ± 16 | 1050 ± 15 | 113 ± 14 | 0.03 |
FVC (L) | 3.8 ± 0.8 | 3.9 ± 0.8 | 3.2 ± 0.6 | 3.2 ± 0.9 | 3.9 ± 0.8 | 0.02 |
FVC (%) | 110 ± 16 | 113 ± 16 | 98 ± 16 | 100 ± 17 | 110 ± 16 | 0.28 |
FEV1.0 (L) | 2.8 ± 0.6 | 2.0 ± 0.7 | 2.5 ± 0.6 | 3.1 ± 0.8 | 2.8 ± 0.8 | 0.15 |
FEV 1.0(%) | 102 ± 17 | 104 ± 15 | 101 ± 17 | 94 ± 24 | 103 ± 16 | 0.64 |
%FEV1.0 | 75 ± 7.5 | 74 ± 7.7 | 78 ± 8.6 | 76 ± 7.1 | 79 ± 4.3 | 0.95 |
V50 | 65 ± 25 | 62 ± 22 | 69 ± 31 | 62 ± 21 | 67 ± 29 | 0.37 |
V25 | 65 ± 25 | 37 ± 19 | 51 ± 39 | 33 ± 14 | 45 ± 18 | 0.18 |
V50/25 | 5.0 ± 4.1 | 5.4 ± 4.2 | 5.1 ± 3.0 | 4.1 ± 1.0 | 5.0 ± 4.2 | 0.21 |
DL CO(%) | 86 ± 21 | 92 ± 20 | 71 ± 16 | 78 ± 20 | 86 ± 21 | 0.01 |
FeNO (ppb) | 25 ± 15 | 25 ± 15 | 16 ± 7.5 | 29 ± 29 | 27 ± 10 | 0.24 |
All data are expressed as mean + SD values. |
The P-values are derived by ANOVA with Turkey’s post hoc tests. |
VC: Vital Capacity; FVC: Forced Vital Capacity; FEV: Forced Expiratory volume; MMF: maximal mid-expiratory flow |
According to the blood test results (see Table 4), the number of white blood cells and liver function parameters increased in Clusters 3 and 4. High-sensitivity test values that detect C-reactive protein (CRP) also increased, particularly in Cluster 3.
Table 4
| All Clusters (n = 97) | Cluster 1 (n = 49) | Cluster 2 (n = 6) | Cluster 3 (n = 11) | Cluster 4 (n = 31) | P-value |
WBC, mL | 6.6 ± 1.7 | 6.5 ± 1.4 | 5.7 ± 1.6 | 7.4 ± 2.1 | 7.0 ± 2.1 | 0.315 |
T-bilirubin, mg/dl | 0.57 ± 0.28 | 0.59 ± 0.28 | 0.62 ± 0.23 | 0.53 ± 0.36 | 0.55 ± 0.27 | 0.843 |
AST, U/L | 27.7 ± 16.2 | 23 ± 13 | 23 ± 15 | 34 ± 51 | 35 ± 23 | 0.34 |
ALT, U/L | 35.0 ± 32.0 | 28 ± 23 | 18 ± 13 | 27 ± 24 | 48 ± 55 | < 0.0001 |
HDL-C, mg/dl | 50 ± 13 | 50 ± 12 | 54 ± 16 | 51 ± 20 | 47 ± 11 | 0.85 |
LDL-C, mg/dl | 115 ± 35 | 120 ± 27 | 95 ± 36 | 119 ± 24 | 115 ± 35 | 0.21 |
TG, mg/dl | 198 ± 195 | 189 ± 131 | 103 ± 42 | 200 ± 92 | 199 ± 95 | 0.35 |
eGFR ml/min/1.73 m2 | 69 ± 22 | 71 ± 15 | 43 ± 34 | 66 ± 17 | 70 ± 28 | 0.234 |
UA, mg/dl | 5.9 ± 1.6 | 6.3 ± 1.9 | 6.0 ± 1.3 | 6.4 ± 1.4 | 5.6 ± 1.5 | 0.605 |
h-CRP, ng/ml | 0.19 ± 0.27 | 0.21 ± 0.27 | 0.21 ± 0.32 | 0.36 ± 0.14 | 0.26 ± 0.29 | 0.276 |
HbA1c, % | 6.0 ± 4.6 | 6.0 ± 0.6 | 6.0 ± 0.6 | 6.2 ± 0.4 | 6.1 ± 0.5 | 0.62 |
NT-proBNP, pg/ml | 434 ± 300 | 81.0 ± 166 | 355 ± 972 | 68.5 ± 148 | 238 ± 481 | 0.775 |
All data are expressed as mean + SD values. |
The P-values are derived by ANOVA with Turkey’s post hoc tests. |
WBC: White blood cells; AST: aspartate aminotransferase; ALT: alanine aminotransferase; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; eGFR: estimated glomerular filtration rate; UA: uric acid; h-CRP: high-sensitivity C-reactive protein; HbA1c: hemoglobin A1c; NT por BNP: N-terminal pro-brain natriuretic peptide |
Cluster analysis
Cluster 1 (49 subjects, 50.5%) had severe OSAS, were obese, and normal leptin level. Cluster 1 primarily included middle-aged participants (mean age: 57 ± 12 years). The mean BMI of patients was 26 ± 2.6. Based on the BMI classification (normal weight, 18.5–24.9; overweight, 25.0–29.9; and obese, > 30), these patients were obese. The mean ESS score of this cluster was 8.7 ± 4.8, which indicates non-symptomatic excessive daytime sleepiness (EDS). The mean AHI, however, was 40 ± 15, which is below the overall average. Leptin and adiponectin levels were low compared to other clusters.
Cluster 2 (6 subjects, 6.2%) had the most severe OSAS, were obese, normal leptin levels, and high adiponectin levels. This cluster also mainly included older participants (mean age: 65 ± 13 years). Their mean BMI was 28 ± 5.8, indicating that they were mildly overweight. The mean ESS score of this cluster was 7.3 ± 3.6, which is low, indicating that this cluster had the lowest likelihood of presenting with EDS symptoms among all clusters (Table 1). However, the AHI was 60 ± 20, indicating severe apnea and hypopnea. Leptin levels were normal, and this cluster had the highest adiponectin levels of all clusters; however, the leptin/adiponectin ratio was the lowest among all clusters.
Cluster 3 (11 subjects, 11.3%) had the most severe OSAS, severe obesity, and the highest leptin levels. This cluster was centered on middle-aged patients (mean age: 52 ± 15 years). The mean BMI of patients in this cluster was 34 ± 6.7, which indicates that they had severe obesity. The mean ESS score was 9.4 ± 4.8 (Table 1). The AHI was 72 ± 25, which is far higher than the overall mean AHI. This cluster accordingly comprised the most severe OSAS patients who had severe obesity (Table 2). Leptin levels and the leptin/adiponectin ratio were the highest of all clusters.
Cluster 4 (31 subjects, 32%) had the most severe OSAS, severe obesity, and high leptin levels. It mainly included middle-aged patients (mean age: 51 ± 12 years). The mean BMI was 33 ± 3.5, indicating severe obesity. The mean ESS score was 8.7 ± 5.3 (Table 1). The AHI was 84 ± 30, which is much higher than the overall AHI mean. This cluster was accordingly composed of the most severe OSAS patients, and had mild-to-moderate symptoms (Table 2). Leptin levels were high and the leptin/adiponectin ratio was comparable to that of Cluster 3.
Table 5 shows AHI, ESS, leptin, adiponectin, h-CRP, BMI before and after 6 months using CPAP. After CPAP treatment, EDS improved in all clusters. In Cluster 3, which had high leptin levels before treatment, leptin levels were significantly reduced after treatment. These results were not accompanied by BMI changes. The adiponectin levels did not change. Clusters 3 and 4 h-CRP value improved but was not significant.
Table 5
Six months after CPAP treatment
| | All Clusters (n = 97) | Cluster 1 (n = 49) | Cluster 2 (n = 6) | Cluster 3 (n = 11) | Cluster 4 (n = 31) | P-value |
AHI/hr | Before | 57 ± 68 | 40 ± 15 | 60 ± 20 | 72 ± 25 | 84 ± 30 | < 0.0001 |
| CPAP | 3.4 ± 3.7 | 3.3 ± 3.0 | 3.5 ± 2.8 | 2.6 ± 0.9 | 3.7 ± 5.2 | 0.67 |
ESS score | Before | 8.7 ± 4.8 | 8.7 ± 4.8 | 7.3 ± 3.6 | 9.4 ± 4.8 | 8.7 ± 5.3 | 0.74 |
| CPAP | 5.5 ± 3.7 | 5.2 ± 3.8 | 5.5 ± 2.3 | 7.6 ± 4.6 | 5.2 ± 3.4 | 0.65 |
Leptin (pg/ml) | Before | 14 ± 11 | 7.0 ± 4.3 | 6.8 ± 3.8 | 39 ± 8.1 | 16 ± 7.0 | < 0.0001 |
| CPAP | 13 ± 12 | 8.3 ± 8.3 | 8.0 ± 2.1 | 27 ± 17 | 17 ± 9.0 | < 0.0001 |
Adiponectin (ng/ml) | Before | 15 ± 7.0 | 15 ± 7.0 | 64 ± 10 | 10 ± 4.1 | 16 ± 10 | 0.35 |
| CPAP | 19 ± 22 | 16 ± 8.0 | 57 ± 9.1 | 10 ± 4.5 | 8.6 ± 4.9 | 0.23 |
h-CRP ng/ml | Before | 0.19 ± 0.27 | 0.21 ± 0.27 | 0.21 ± 0.32 | 0.36 ± 0.14 | 0.26 ± 0.29 | 0.276 |
| CPAP | 0.20 ± 0.58 | 0.22 ± 0.13 | 0.19 ± 0.33 | 0.28 ± 0.31 | 0.18 ± 0.10 | 0.276 |
Body mass index, kg/m2 | Before | 29 ± 5.1 | 26 ± 2.6 | 28 ± 5.8 | 34 ± 6.7 | 33 ± 3.5 | < 0.0001 |
| CPAP | 28 ± 5.2 | 25 ± 2.7 | 27 ± 5.5 | 34 ± 6.2 | 32 ± 4.0 | < 0.0001 |
All data are expressed as mean + SD values. |
The P-values are derived by ANOVA with Turkey’s post hoc tests. |
AHI: apnea hypopnea index; ESS: Epworth Sleepiness Scale; h-CRP: high-sensitivity C-reactive protein; CPAP: continuous positive airway pressure |