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Obstructive sleep apnoea-related respiratory events and desaturation severity are associated with the cardiac response

Salla Hietakoste, Tuomas Karhu, Saara Sillanmäki, Raquel Bailón, Thomas Penzel, Juha Töyräs, Timo Leppänen, Sami Myllymaa, Samu Kainulainen
ERJ Open Research 2022 8: 00121-2022; DOI: 10.1183/23120541.00121-2022
Salla Hietakoste
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
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Tuomas Karhu
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
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Saara Sillanmäki
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
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Raquel Bailón
3Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza, Spain
4Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain
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Thomas Penzel
5Interdisciplinary Sleep Medicine Center, Charité-Universitätsmedizin Berlin, Berlin, Germany
6Dept of Biology, Saratov State University, Saratov, Russian Federation
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Juha Töyräs
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
7Science Service Center, Kuopio University Hospital, Kuopio, Finland
8School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia
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Timo Leppänen
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
8School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia
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Sami Myllymaa
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
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Samu Kainulainen
1Dept of Applied Physics, University of Eastern Finland, Kuopio, Finland
2Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland
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  • FIGURE 1
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    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
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    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
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    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

  • Figures
  • 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 segments39 132
    Events per 5-min segment
     Ev020 873 (53.3%)
     EvQ14663 (11.9%)
     EvQ24997 (12.8%)
     EvQ33752 (9.6%)
     EvQ44847 (12.4%)
    Desaturation severity
     DesSev023 191 (59.3%)
     DesSevQ13985 (10.2%)
     DesSevQ23986 (10.2%)
     DesSevQ33985 (10.2%)
     DesSevQ43985 (10.2%)
    Comorbidities
     Atrial arrhythmia56 (8.7%)
     COPD58 (9.0%)
     Diabetes mellitus, type 13 (0.5%)
     Diabetes mellitus, type 2115 (17.9%)
     Hypothyroidism65 (10.1%)
     Hypertension239 (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 groupHF (ms2)LF (ms2)LF/HFHFNULFNU
      Events per 5-min segment
       Ev0183.6 (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)
       EvQ1198.1 (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)**
       EvQ2207.0 (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)
       EvQ3236.0 (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)
       EvQ4314.9 (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
       DesSev0198.5 (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)##
       DesSevQ1175.5 (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)
       DesSevQ2199.9 (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)##
       DesSevQ3210.6 (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)
       DesSevQ4287.1 (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 groupMean RR (ms)SDNN (ms)RMSSD (ms)pRR50 (%)
        Events per 5-min segment
         Ev0915.3 (815.3–1033.1)42.8 (26.6–67.9)33.3 (18.8–59.5)7.0 (0.8–28.0)
         EvQ1913.2 (814.6–1028.4)53.8 (33.6–84.4)**35.2 (19.2–63.8)7.8 (1.0–27.8)
         EvQ2907.7 (807.4–1026.3)58.9 (38.2–90.4)**36.5 (20.4–66.4)8.4 (1.5–27.8)
         EvQ3898.9 (801.4–1019.1)66.7 (43.3–98.0)**40.7 (22.8–70.2)**9.6 (2.1–27.6)
         EvQ4868.5 (784.2–973.9)**73.9 (49.3–104.6)**47.4 (27.1–80.8)**14.1 (4.1–32.3)**
        Desaturation severity
         DesSev0925.2 (824.3–1044.3)##45.7 (28.3–72.1)##34.7 (19.8–61.2)##8.2 (1.0–29.5)##
         DesSevQ1898.9 (797.0–1010.3)##53.3 (31.4–85.4)**34.1 (17.8–63.2)6.7 (0.8–25.6)
         DesSevQ2897.8 (801.3–1010.6)56.5 (35.0–88.5)**,##35.8 (19.5–64.7)8.2 (1.2–26.4)
         DesSevQ3878.6 (785.0–994.3)**,##60.3 (39.2–91.3)**,##38.5 (21.0–68.2)**8.3 (1.5–26.7)
         DesSevQ4853.6 (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 groupndesatDuration (s)Depth (%)DesSev (%)
          Events per 5-min segment
           Ev00 (0–0)0 (0–0)0 (0–0)0 (0–0)
           EvQ11 (0–1)12.0 (0–29.0)**3.0 (0–3.0)**0.062 (0–0.251)**
           EvQ22 (1–3)27.0 (8.1–39.2)**3.0 (2.0–4.0)**0.335 (0.037–0.825)**
           EvQ34 (2–5)34.8 (24.6–46.3)**4.3 (3.3–6.7)**1.250 (0.500–2.726)**
           EvQ47 (5–8)30.5 (24.4–37.3)**5.7 (4.0–9.6)**2.662 (1.328–4.916)**
          Desaturation severity
           DesSev00 (0–0)0 (0–0)0 (0–0)0 (0–0)
           DesSevQ11 (1–1)22.1 (17.0–30.0)**,##3.0 (3.0–3.0)**,##0.161 (0.105–0.226)**,##
           DesSevQ22 (2–3)31.5 (24.2–41.0)**,##3.5 (3.0–4.0)**,##0.531 (0.402–0.685)**,##
           DesSevQ34 (3–6)34.3 (26.8–43.7)**,##4.3 (3.7–5.3)**,##1.504 (1.166–1.923)**,##
           DesSevQ46 (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

            HFNULFNUMean RRSDNN
            β±set-statβ±set-statβ±set-statβ±set-stat
            Sex−0.048±0.002***−23.20.035±0.002***19.00.038±0.002***23.70.009±0.000***20.0
            Age−0.000±0.000−3.1−0.001±0.000***−17.40.002±0.000***29.9−0.000±0.000***−6.0
            BMI0.001±0.000***9.4−0.002±0.000***−20.3−0.004±0.000***−49.4−0.000±0.000***−17.1
            ESS0.001±0.000***5.5−0.000±0.000−3.2−0.000±0.000−0.90.000±0.000***4.8
            Hypothyroidism0.017±0.003***5.0−0.018±0.003***−5.8−0.000±0.003−0.2−0.007±0.001***−8.8
            Arrhythmias0.090±0.004***22.5−0.073±0.004***−20.70.073±0.003***23.90.036±0.001***39.5
            Hypertension0.006±0.0022.8−0.018±0.002***−9.30.002±0.0021.1−0.007±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***−32.20.005±0.000***11.8−0.008±0.000***−23.50.004±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.

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            Obstructive sleep apnoea-related respiratory events and desaturation severity are associated with the cardiac response
            Salla Hietakoste, Tuomas Karhu, Saara Sillanmäki, Raquel Bailón, Thomas Penzel, Juha Töyräs, Timo Leppänen, Sami Myllymaa, Samu Kainulainen
            ERJ Open Research Oct 2022, 8 (4) 00121-2022; DOI: 10.1183/23120541.00121-2022

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            Obstructive sleep apnoea-related respiratory events and desaturation severity are associated with the cardiac response
            Salla Hietakoste, Tuomas Karhu, Saara Sillanmäki, Raquel Bailón, Thomas Penzel, Juha Töyräs, Timo Leppänen, Sami Myllymaa, Samu Kainulainen
            ERJ Open Research Oct 2022, 8 (4) 00121-2022; DOI: 10.1183/23120541.00121-2022
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