Figures
- FIGURE 1
Inclusion and exclusion criteria for the patient and 5-min segment selection. PSG: polysomnography; OSA: obstructive sleep apnoea; ECG: electrocardiogram; Ev: event rate; Ev0=0 events per 5 min, EvQ1=1 event per 5 min<EvQ2≤3 events per 5 min<EvQ3≤5 events per 5 min<EvQ4; DesSev: desaturation severity; DesSev0=0%, DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4.
- FIGURE 2
Median power spectral densities (PSDs) in the severity groups pooled based on the respiratory event rate (Ev) within the 5-min segments. Vertical dashed lines separate the frequency bands used in heart rate variability analyses: the low-frequency band (0.04–0.15 Hz) and the high-frequency band (0.15–0.40 Hz). Ev0=0 events per 5 min, EvQ1=1 event per 5 min<EvQ2≤3 events per 5 min<EvQ3≤5 events per 5 min<EvQ4.
- FIGURE 3
Median power spectral densities (PSDs) in the groups pooled based on the desaturation severity (DesSev) within the 5-min segments. Vertical dashed lines separate the frequency bands used in heart rate variability analyses: the low-frequency band (0.04–0.15 Hz) and the high-frequency band (0.15–0.40 Hz). DesSev0=0%, DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4.
Tables
- TABLE 1
Demographic characteristics of the study population
Characteristics Patients (male %) 642 (54.4%) Age (years) 53.4 (42.9–63.1) BMI (kg·m−2) 34.4 (28.9–40.0) AHI (events·h−1) 16.9 (7.7–36.0) OSA None (AHI<5) 107 (16.7%) Mild (5≤AHI<15) 185 (28.8%) Moderate (15≤AHI<30) 163 (25.4%) Severe (AHI≥30) 187 (29.1%) ODI3% (events·h−1) 13.6 (4.6–33.1) Total sleep time (min) 330.3 (287.5–370.0) All 5-min segments 39 132 Events per 5-min segment Ev0 20 873 (53.3%) EvQ1 4663 (11.9%) EvQ2 4997 (12.8%) EvQ3 3752 (9.6%) EvQ4 4847 (12.4%) Desaturation severity DesSev0 23 191 (59.3%) DesSevQ1 3985 (10.2%) DesSevQ2 3986 (10.2%) DesSevQ3 3985 (10.2%) DesSevQ4 3985 (10.2%) Comorbidities Atrial arrhythmia 56 (8.7%) COPD 58 (9.0%) Diabetes mellitus, type 1 3 (0.5%) Diabetes mellitus, type 2 115 (17.9%) Hypothyroidism 65 (10.1%) Hypertension 239 (37.2%) Data are presented as median (interquartile range) for continuous variables and as n (%) for discrete variables. BMI: body mass index; AHI: apnoea-hypopnoea index; OSA: obstructive sleep apnoea; ODI3%: oxygen desaturation index based on American Academy of Sleep Medicine 2012 scoring criteria (desaturation ≥3%); Ev0: reference group with 0 respiratory events starting during the 5-min segment; EvQ1–4: severity groups pooled based on the number of respiratory events (apnoeas/hypopnoeas) starting during the 5-min segment (EvQ1=1<EvQ2≤3<EvQ3≤5<EvQ4); DesSev0: reference group with desaturation severity of 0 during the 5-min segment; DesSevQ1–4: severity groups pooled based on the desaturation severity in the 5-min segment (0%<DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4); COPD: chronic obstructive pulmonary disease.
- TABLE 2
Frequency-domain HRV parameter values in the severity groups based on the Ev and the DesSev in the 5-min segments
Severity group HF (ms2) LF (ms2) LF/HF HFNU LFNU Events per 5-min segment Ev0 183.6 (57.5–523.1) 160.9 (56.7–451.1) 0.934 (0.433–2.012) 0.517 (0.332–0.698) 0.483 (0.302–0.668) EvQ1 198.1 (57.1–585.6) 225.9 (76.7–644.0)** 1.243 (0.584–2.504)** 0.446 (0.285–0.631)** 0.554 (0.369–0.715)** EvQ2 207.0 (62.5–608.2) 258.1 (98.4–708.9)** 1.385 (0.647–2.731) 0.419 (0.268–0.607) 0.581 (0.393–0.732) EvQ3 236.0 (76.0–653.6) 327.0 (129.6–866.2)** 1.421 (0.730–2.805) 0.413 (0.263–0.578) 0.587 (0.422–0.737) EvQ4 314.9 (99.5–841.0)** 536.3 (203.9–1292.3)** 1.745 (0.817–3.664)** 0.364 (0.214–0.550)** 0.636 (0.450–0.786)** Desaturation severity DesSev0 198.5 (63.5–550.3)## 186.6 (64.5–525.5)## 1.004 (0.462–2.127)## 0.499 (0.320–0.684)## 0.501 (0.316–0.680)## DesSevQ1 175.5 (48.0–557.1) 213.3 (69.9–632.9) 1.303 (0.597–2.693) 0.434 (0.271–0.626) 0.566 (0.374–0.729) DesSevQ2 199.9 (60.5–577.7) 229.5 (83.2–653.0)## 1.256 (0.577–2.559)## 0.443 (0.281–0.634)## 0.557 (0.366–0.719)## DesSevQ3 210.6 (65.5–652.8) 282.4 (103.9–757.3)**,## 1.347 (0.654–2.788) 0.426 (0.264–0.605) 0.574 (0.395–0.736) DesSevQ4 287.1 (92.8–861.0)** 479.7 (173.8–1310.3)** 1.747 (0.818–3.462)** 0.364 (0.224–0.550)** 0.636 (0.450–0.776)** The median of frequency-domain HRV parameter values was calculated from each 5-min RR interval segment. Data are presented as the median (interquartile range). Statistical significance of differences between 1) Ev groups, 2) DesSev groups and 3) the corresponding Ev and DesSev groups was assessed using the Wilcoxon signed-rank test. Bolded values denote a statistically significant (p<0.01) difference compared to the corresponding reference group.
HRV: heart rate variability; Ev: respiratory event rate; Ev0: reference group with 0 respiratory events starting during the 5-min segment; EvQ1–4: severity groups pooled based on the number of respiratory events (apnoeas/hypopnoeas) starting during the 5-min segment (EvQ1=1<EvQ2≤3<EvQ3≤5<EvQ4); DesSev: desaturation severity; DesSev0: reference group with desaturation severity of 0% during the 5-min segment; DesSevQ1–4: severity groups pooled based on the desaturation severity during the 5-min segment (0%<DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4); HF: total power in the high-frequency band (0.15–0.40 Hz); LF: total power in the low-frequency band (0.04–0.15 Hz); HFNU: normalised power in the high-frequency band (HF/(HF+LF)); LFNU: normalised power in the low-frequency band (LF/(HF+LF)). **: statistically significant difference (p<0.01) compared to all other Ev or DesSev groups; ##: statistically significant difference (p<0.01) compared to the corresponding Ev group.
- TABLE 3
Time-domain HRV parameter values in the severity groups based on the Ev and the DesSev in the 5-min segments
Severity group Mean RR (ms) SDNN (ms) RMSSD (ms) pRR50 (%) Events per 5-min segment Ev0 915.3 (815.3–1033.1) 42.8 (26.6–67.9) 33.3 (18.8–59.5) 7.0 (0.8–28.0) EvQ1 913.2 (814.6–1028.4) 53.8 (33.6–84.4)** 35.2 (19.2–63.8) 7.8 (1.0–27.8) EvQ2 907.7 (807.4–1026.3) 58.9 (38.2–90.4)** 36.5 (20.4–66.4) 8.4 (1.5–27.8) EvQ3 898.9 (801.4–1019.1) 66.7 (43.3–98.0)** 40.7 (22.8–70.2)** 9.6 (2.1–27.6) EvQ4 868.5 (784.2–973.9)** 73.9 (49.3–104.6)** 47.4 (27.1–80.8)** 14.1 (4.1–32.3)** Desaturation severity DesSev0 925.2 (824.3–1044.3)## 45.7 (28.3–72.1)## 34.7 (19.8–61.2)## 8.2 (1.0–29.5)## DesSevQ1 898.9 (797.0–1010.3)## 53.3 (31.4–85.4)** 34.1 (17.8–63.2) 6.7 (0.8–25.6) DesSevQ2 897.8 (801.3–1010.6) 56.5 (35.0–88.5)**,## 35.8 (19.5–64.7) 8.2 (1.2–26.4) DesSevQ3 878.6 (785.0–994.3)**,## 60.3 (39.2–91.3)**,## 38.5 (21.0–68.2)** 8.3 (1.5–26.7) DesSevQ4 853.6 (771.4–952.5)**,## 75.5 (51.8–106.6)**,## 46.7 (25.9–82.3)** 12.2 (3.6–30.6)**,## The median of time-domain HRV parameter values was calculated from each 5-min RR interval segment. Data are presented as median (interquartile range). Statistical significance of differences between 1) Ev groups, 2) DesSev groups and 3) the corresponding Ev and DesSev groups was assessed using the Wilcoxon signed-rank test. The bolded values denote a statistically significant (p<0.01) difference compared to the corresponding reference group. HRV: heart rate variability; Ev: respiratory event rate; Ev0: reference group with 0 respiratory events starting during the 5-min segment; EvQ1–4: severity groups pooled based on the number of respiratory events (apnoeas/hypopnoeas) starting during the 5-min segment (EvQ1=1<EvQ2≤3<EvQ3≤5<EvQ4); DesSev: desaturation severity; DesSev0: reference group with desaturation severity of 0% during the 5-min segment; DesSevQ1–4: severity groups pooled based on the desaturation severity during the 5-min segment (0%<DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4); SDNN: standard deviation of RR intervals (artefacts corrected); RMSSD: root mean square of successive differences; pRR50: the number of adjacent RR intervals differing more than 50 ms. **: statistically significant difference (p<0.01) compared to all other Ev or DesSev groups; ##: statistically significant difference (p<0.01) compared to the corresponding Ev group.
- TABLE 4
Desaturation characteristics in the 5-min segments in the severity groups
Severity group ndesat Duration (s) Depth (%) DesSev (%) Events per 5-min segment Ev0 0 (0–0) 0 (0–0) 0 (0–0) 0 (0–0) EvQ1 1 (0–1) 12.0 (0–29.0)** 3.0 (0–3.0)** 0.062 (0–0.251)** EvQ2 2 (1–3) 27.0 (8.1–39.2)** 3.0 (2.0–4.0)** 0.335 (0.037–0.825)** EvQ3 4 (2–5) 34.8 (24.6–46.3)** 4.3 (3.3–6.7)** 1.250 (0.500–2.726)** EvQ4 7 (5–8) 30.5 (24.4–37.3)** 5.7 (4.0–9.6)** 2.662 (1.328–4.916)** Desaturation severity DesSev0 0 (0–0) 0 (0–0) 0 (0–0) 0 (0–0) DesSevQ1 1 (1–1) 22.1 (17.0–30.0)**,## 3.0 (3.0–3.0)**,## 0.161 (0.105–0.226)**,## DesSevQ2 2 (2–3) 31.5 (24.2–41.0)**,## 3.5 (3.0–4.0)**,## 0.531 (0.402–0.685)**,## DesSevQ3 4 (3–6) 34.3 (26.8–43.7)**,## 4.3 (3.7–5.3)**,## 1.504 (1.166–1.923)**,## DesSevQ4 6 (5–8) 37.8 (30.7–47.2)**,## 9.0 (6.5–13.6)**,## 4.471 (3.305–6.948)**,## Data are presented as median (interquartile range). Statistical significance of differences between 1) Ev groups, 2) DesSev groups and 3) the corresponding Ev and DesSev groups was assessed using the Wilcoxon signed-rank test. The bolded values denote a statistically significant (p<0.01) difference compared to the corresponding reference group. Ev0: reference group with 0 respiratory events starting during the 5-min segment; EvQ1–4: severity groups pooled based on the number of respiratory events (apnoeas/hypopnoeas) starting during the 5-min segment (EvQ1=1<EvQ2≤3<EvQ3≤5<EvQ4); DesSev0: reference group with desaturation severity of 0% during the 5-min segment; DesSevQ1–4: severity groups pooled based on the desaturation severity during the 5-min segment (0%<DesSevQ1≤0.305%<DesSevQ2≤0.906%<DesSevQ3≤2.463%<DesSevQ4); ndesat: median number of desaturations within the 5-min segments.**: statistically significant difference (p<0.01) compared to all other Ev or DesSev groups; ##: statistically significant difference (p<0.01) compared to the corresponding Ev group.
- TABLE 5
Covariate-adjusted regression analysis to investigate the effect of covariates on selected heart rate variability parameters
HFNU LFNU Mean RR SDNN β±se t-stat β±se t-stat β±se t-stat β±se t-stat Sex −0.048±0.002*** −23.2 0.035±0.002*** 19.0 0.038±0.002*** 23.7 0.009±0.000*** 20.0 Age −0.000±0.000 −3.1 −0.001±0.000*** −17.4 0.002±0.000*** 29.9 −0.000±0.000*** −6.0 BMI 0.001±0.000*** 9.4 −0.002±0.000*** −20.3 −0.004±0.000*** −49.4 −0.000±0.000*** −17.1 ESS 0.001±0.000*** 5.5 −0.000±0.000 −3.2 −0.000±0.000 −0.9 0.000±0.000*** 4.8 Hypothyroidism 0.017±0.003*** 5.0 −0.018±0.003*** −5.8 −0.000±0.003 −0.2 −0.007±0.001*** −8.8 Arrhythmias 0.090±0.004*** 22.5 −0.073±0.004*** −20.7 0.073±0.003*** 23.9 0.036±0.001*** 39.5 Hypertension 0.006±0.002 2.8 −0.018±0.002*** −9.3 0.002±0.002 1.1 −0.007±0.001*** −14.7 COPD −0.004±0.004 −1.1 −0.033±0.003*** −10.0 −0.080±0.003*** −28.0 −0.011±0.001*** −13.1 DesSev −0.015±0.000*** −32.2 0.005±0.000*** 11.8 −0.008±0.000*** −23.5 0.004±0.000*** 39.7 Sex and all comorbidities are considered as categorical variables in the regression model. BMI: body mass index; ESS: Epworth Sleepiness Scale; COPD: chronic obstructive pulmonary disease; DesSev: desaturation severity; β: estimated coefficient for the regression model; t-stat: t-statistic for a test that the coefficient is zero; HFNU: normalised power in the high-frequency band (HF/(HF+LF)); LFNU: normalised power in the low-frequency band (LF/(HF+LF)); SDNN: standard deviation of RR intervals (artefacts corrected). ***: p<0.001.
