Low Arousal Threshold: A Potential Bridge Between OSA and Periodic Limb Movements of Sleep

Figures & data

Figure 1 Study flow diagram. In this study, 793 OSA patients with an AHI of ≥ 5 were enrolled. Among the 793 patients, 720 participants were eventually included in the study. The same inclusion and exclusion criteria were used for the MrOS patients.

Abbreviations: PD, Parkinson’s disease; MSA, multiple system atrophy; RLS, restless leg syndrome; PLMI, periodic leg movement index; PLMS, periodic leg movement in sleep; ArTH, arousal threshold.

Table 1 Subject Characteristics and Polysomnography Parameters in OSA-PLMS and OSA-Only Group

	Internal Cohort			MrOS Study Cohort
	OSA-Only (N=625)	OSA-PLMS (N=95)	p	OSA-Only (N=922)	OSA-PLMS (N=1367)	p
Clinical Characteristics
Age	42 (35–53)	61 (53–70)	<0.001	75 (71–79)	76 (72–81)	<0.001
Gender (male)	534 (85%)	79 (83%)	0.7		All Male
Ethnicity (white)		All Chinese		800 (87%)	1275 (93%)	<0.001
BMI	26.2 (24.2–28.3)	26.0 (23.9–28.3)	>0.9	27 (25–30)	27 (25–30)	0.8
ESS	8.0 (5.0–12.0)	9.0 (5.0–12.5)	0.6	6 (3–8)	6 (3–8)	0.6
Hypertension	205 (33%)	52 (55%)	<0.001	451 (49%)	711 (52%)	0.2
Diabetes	29 (4.6%)	19 (20%)	<0.001	109 (12%)	201 (15%)	0.056
Arrhythmia	43 (6.9%)	12 (13%)	0.049	84 (9.1%)	153 (11%)	0.13
Stroke	47 (7.5%)	20 (21%)	<0.001	29 (3.1%)	50 (3.7%)	0.6
CAD	8 (1.3%)	2 (2.1%)	0.6	143 (16%)	268 (20%)	0.014
Asthma	8 (1.3%)	1 (1.1%)	>0.9	58 (6.3%)	113 (8.3%)	0.093
COPD	5 (0.8%)	1 (1.1%)	0.6	54 (5.9%)	61 (4.5%)	0.2
PSG Parameters
TST, min	429 (373–472)	394 (314–455)	<0.001	364 (323–401)	359 (315–400)	0.057
Sleep Efficiency, %	87 (77–93)	78 (63–85)	<0.001	77 (69–84)	78 (69–85)	>0.9
Sleep Latency, min	4 (2–11)	6 (1–16)	0.3	17 (8–29)	15 (8–28)	0.6
NREM 1, %	13 (8–20)	21 (13–36)	<0.001	6.0 (4.0–9.0)	6.0 (4.0–9.0)	0.7
NREM 2, %	51 (45–58)	44 (34–53)	<0.001	62 (56–68)	64 (57–70)	<0.001
NREM 3, %	15 (10–20)	14 (5–20)	0.072	11 (4–17)	9 (3–15)	<0.001
REM, %	19 (15–23)	17 (12–23)	0.11	20 (15–24)	19 (14–23)	0.056
ODI, N/hr	20 (13–27)	15 (6–33)	0.026	20 (12–33)	19 (12–31)	0.2
AHI, N/hr	25 (15–34)	21 (10–39)	0.2	18 (10–30)	16 (10–28)	0.089
AvgSaO2, %	95 (95–96)	95 (94–96)	0.081	93 (74–95)	93 (74–95)	0.6
MinSaO2, %	81 (77–84)	84 (77–87)	<0.001	84 (80–87)	85 (81–88)	0.057
TS90, %	2.8 (1.1–5.2)	1.4 (0.2–8.3)	0.10	1 (0–5)	1 (0–4)	0.048
Arousal Index, N/hr	16 (10–24)	17 (8–28)	0.5	21 (16–29)	23 (17–32)	<0.001

Note: Values were expressed as median (interquartile range in brackets) or count (percentage).

Abbreviations: PLMS, periodic limb movement syndrome; OSA, obstructive sleep apnea; BMI, body mass index; ESS, Epworth Sleepiness Scale; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; TST, total sleep time; NREM, non-rapid eye movement; REM, rapid eye movement; ODI, oxygen desaturation index; AHI, apnea-hypopnea index; avgSaO₂, mean arterial oxygen saturation; minSaO₂, lowest arterial oxygen saturation; TS90, percentage of total sleep time at oxygen saturation level < 90%.

Table 2 Arousal Threshold and Its Predictors in OSA Patients in the OSA-PLMS and OSA-Only Groups

	OSA-Only	OSA-PLMS	χ2	p
	(N = 625)	(N = 95)
Low ArTH	125 (20%)	56 (58.9%)	66.47	< 0.001
AHI < 30	370 (59.2%)	63 (66.3%)	1.742	0.187
minSaO₂ > 82.5%	217 (34.7%)	56 (58.9%)	20.563	< 0.001
FHypopnea > 58.3%	74 (11.8%)	23 (24.2%)	10.826	< 0.001

Note: Values were expressed as count (percentage).

Abbreviations: PLMS, periodic limb movement syndrome; OSA, obstructive sleep apnea; AHI, apnea-hypopnea index; minSaO₂, lowest arterial oxygen saturation; ArTH, arousal threshold; F_Hypopnea, fraction of hypopnea in all respiratory events.

Table 3 Regression Analyses of Factors Associated with PLMS Among OSA Participants

	Univariable Analysis			Multivariable Analysis
	β	p	OR (95% CI)	β	p		OR (95% CI)
Age	0.088	<0.001	1.092 (1.072–1.113)	0.07	<0.001		1.073 (1.049–1.097)
Hypertension	0.907	<0.001	2.478 (1.600–3.836)	−0.04	0.888		0.961 (0.549–1.682)
Diabetes	1.637	<0.001	5.138 (2.748–9.607)	0.923	0.025		2.516 (1.123–5.636)
Arrhythmia	0.671	0.053	1.957 (0.991–3.862)	−0.119	0.783		2.516 (1.123–5.636)
Stroke	1.123	<0.001	3.074 (1.714–5.513)	0.043	0.909		1.044 (0.499–2.184)
SleepEff	−0.037	<0.001	0.964 (0.951–0.977)	0.004	0.788		1.004 (0.975–1.034)
NREM 1, %	0.056	<0.001	1.057 (1.040–1.074)	0.018	0.202		1.018 (0.991–1.045)
NREM 2, %	−0.048	<0.001	0.953 (0.936–0.971)	−0.018	0.186		0.982 (0.955–1.009)
ODI	0.012	0.153	1.012 (0.996–1.028)	0.033	0.002		1.033 (1.012–1.055)
TST	−0.004	<0.001	0.996 (0.993–0.998)	−0.001	0.764		0.999 (0.995–1.004)
MinSaO₂	0.034	0.049	1.035 (1.000–1.071)	Not included
Low ArTH	1.748	<0.001	5.744 (3.650–9.038)	2.173	<0.001		8.781 (4.73–16.301)

Note: Odds ratios were expressed as estimate (95% confidence interval).

Abbreviations: PLMS, periodic limb movement syndrome; OSA, obstructive sleep apnea; SleepEff, sleep efficiency; NREM, non-rapid eye movement; ODI, oxygen desaturation index; TST, total sleep time; minSaO₂, lowest arterial oxygen saturation; ArTH, arousal threshold.

Table 4 Risk of PLMS by Arousal Threshold in the MrOS Dataset

		Low ArTH
	β	OR (95% CI)	p
Model 1: Age + BMI + Race	0.278	1.32 (1.08–1.61)	0.006
Model 2: Model 1 + SleepEff + NREM2 + avgSaO₂ + TS90	0.282	1.33 (1.07–1.64)	0.009
Model 3: Model 2 + Hypertension+ Diabetes + Arrhythmia + Asthma + Stroke	0.285	1.33 (1.08–1.64)	0.009

Note: Odds ratios were expressed as estimate (95% confidence interval).

Abbreviations: PLMS, periodic limb movement syndrome; ArTH, arousal threshold; BMI, body mass index; SleepEff, sleep efficiency; NREM, non-rapid eye movement; avgSaO₂, average arterial oxygen saturation; TS90, percentage of total sleep time at oxygen saturation level < 90%.