Sleep disordered breathing and haemoglobin A1c levels within or over normal range and ageing or sex differences: the Nagahama study.

Recently an association between blood glucose dysregulation and sleep disruption was suggested. The association between sleep disordered breathing, most of which is due to obstructive sleep apnea (OSA) in the general population, and diabetic severity, as well as the impact of antidiabetic treatment, remains unclear. This study aimed to investigate these associations as well as age and sex differences. This cross-sectional study evaluated 7,680 community participants as the main cohort (population-based cohort). OSA was assessed by the 3% oxygen desaturation index from pulse oximetry, which was corrected for sleep duration obtained by wrist actigraphy. For arguing the limitations for using pulse oximetry, 597 hospitalised patients, who were assessed by the apnea-hypopnea index from attended polysomnography, were also evaluated as the validation cohort (hospital-based cohort). Moderate-to-severe OSA was more prevalent as haemoglobin A1c (HbA1c) levels increased (<5.6%/5.6%-<6.5%/6.5%-<7.5%/≥7.5%, respectively) in both cohorts (p < 0.001), but only in those without antidiabetic treatment. The HbA1c level was an independent factor for moderate-to-severe OSA (population-based cohort, odds ratio [OR] 1.26, 95% confidence interval [CI] 1.10-1.45; hospital-based cohort, OR 1.69, 95% CI 1.22-2.33, per 1% increase). These associations were more prominent in the middle-aged (aged <60 years) than in the elderly (aged ≥60 years) and in women than in men in both cohorts. The prevalence of moderate-to-severe OSA in patients with antidiabetic treatment in the hospital-based cohort was ≥75% regardless of HbA1c levels. In conclusion, an association between the prevalence of OSA and HbA1c level even within or over the normal range was found only in patients without antidiabetic treatment and was more prominent in the middle-aged and in women.

Sleep disordered breathing and metabolic comorbidities across sex and menopausal status in East Asians: the Nagahama Study.

It is well known that the prevalence of sleep disordered breathing (SDB) is increased in patients with obesity or metabolic comorbidities. However, the way in which the prevalence of SDB increases in relation to comorbidities according to the severity of obesity remains unclear.This cross-sectional study evaluated 7713 community participants using nocturnal oximetry ≥2 nights. SDB was assessed by the 3% oxygen desaturation index corrected for sleep duration obtained by wrist actigraphy (acti-ODI3%). SDB severity was defined by acti-ODI3%. Obesity was defined as body mass index ≥25 kg·m-2The prevalence of SDB was 41.0% (95% CI 39.9-42.1%), 46.9% (45.8-48.0%), 10.1% (9.5-10.8%) and 2.0% (1.7-2.3%) in normal, mild, moderate and severe SDB, respectively, with notable sex differences evident (males>post-menopausal females>premenopausal females). Comorbidities such as hypertension, diabetes and metabolic syndrome were independently associated with the prevalence of moderate-to-severe SDB, and coincidence of any one of these with obesity was associated with a higher probability of moderate-to-severe SDB (hypertension OR 8.2, 95% CI 6.6-10.2; diabetes OR 7.8, 95% CI 5.6-10.9; metabolic syndrome OR 6.7, 95% CI 5.2-8.6). Dyslipidaemia in addition to obesity was not additively associated with the prevalence of moderate-to-severe SDB. The number of antihypertensive drugs was associated with SDB (p for trend <0.001). Proportion of a high cumulative percentage of sleep time with oxygen saturation measured by pulse oximetry <90% increased, even among moderate-to-severe SDB with increases in obesity.Metabolic comorbidities contribute to SDB regardless of the degree of obesity. We should recognise the extremely high prevalence of moderate-to-severe SDB in patients with obesity and metabolic comorbidities.

Lifestyle habits associated with nocturnal urination frequency: The Nagahama study.

BACKGROUND: Nocturia is a risk factor for poor quality of life and increased mortality. This study was aimed to clarifying dietary habits, eating behaviors, and sleep characteristics associated with nocturia to identify modifiable lifestyle factors for nocturia. METHODS: This cross-sectional study included 5683 community residents (64.5 ± 7.7 years old). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. The frequency of food intake, unfavorable eating behaviors, and sleep characteristics that may have influence on salt intake and wasting were obtained using a structured questionnaire. RESULTS: The frequency of nocturnal urination was increased with age (ß = .312, P < .001). Other basic factors associated with the frequency were the male sex (ß = .090), hypertension (ß = .038), sleep apnea (ß = .030), B-type natriuretic peptide level (ß = .089), and spot urine sodium excretion (ß = -.058). Dietary factors independently associated with nocturnal urination frequency were coffee (≥1 time/day: ß = -.059, P < .001) and green vegetable consumption (≥1 time/week: ß = -.042, P = .001), whereas habitual intake of dairy products, miso soup, and alcohol were not associated with urination frequency. Later bedtime was inversely associated with nocturnal urination frequency independent of sleep duration (before 23:00: ß = -.096; before 24:00: ß = -.225; after midnight: ß = -.240; all P < .001). CONCLUSION: Coffee and green vegetable consumption and later bedtime but not sleep duration are lifestyle factors associated with nocturnal urination frequency.

Effects of bright light exposure during daytime on peripheral clock gene expression in humans.

Light is the strongest synchronizer controlling circadian rhythms. The intensity and duration of light change throughout the year, thereby influencing body weight, food preferences, and melatonin secretion in humans and animals. Although the expression of clock genes has been examined using human samples, it currently remains unknown whether bright light during the daytime affects the expression of these genes in humans. Therefore, we herein investigated the effects of bright light exposure during the daytime on clock gene expression in the hair follicular and root cells of the human scalp. Seven healthy men (20.4 ± 2.2 years old; 172.3 ± 5.8 cm; 64.3 ± 8.5 kg; BMI 21.7 ± 3.1 kg/m2, mean ± SD) participated in this study. Subjects completed 3-day experimental sessions twice in 1 month during which they were exposed to bright and dim light conditions. The mRNA expression of Per1-3, Cry1-2, Rev-erb-α (Nr1d1), Rev-erb-ß (Nr1d2), and Dec1 was analyzed using branched DNA probes. No significant changes were observed in the expression of Per1, Per2, Per3, Cry1, Cry2, Rev-erb-α (Nr1d1), or Dec1 following exposure to bright light conditions. However, the expression of Rev-erb-ß (Nr1d2) tended to be stronger under bright light than dim light conditions. These results suggest that the bright light stimulus did not influence the expression of clock genes in humans. Long-lasting bright light exposure during the daytime may be required to change the expression of clock genes in humans.

Associations among chronic obstructive pulmonary disease and sleep-disordered breathing in an urban male working population in Japan.

BACKGROUND: There are few reports about sleep disturbances in patients with chronic obstructive pulmonary disease (COPD) in Asian countries. OBJECTIVES: To investigate the associations between sleep-disordered breathing (SDB) with hypoxemia and sleep quality, including sleep duration, in patients with COPD, we measured SDB and sleep quality including the objective sleep duration determined by an actigraph and portable monitoring. METHODS: A cross-sectional epidemiological health survey of 303 male employees (means ± SD: age 43.9 ± 8.2 years; BMI 24.0 ± 3.1) was conducted. Sleep quality was measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). A respiratory disturbance index (RDI) ≥5 indicated SDB. RESULTS: Nineteen subjects (6.3%) had COPD. Among these, 11 (3.6%) had COPD with SDB (overlap syndrome). Sleep duration, ESS, and PSQI scores were not significantly different between COPD patients and normal control subjects. However, COPD patients had significantly longer sleep latency (p = 0.019), a lower sleep efficiency (p = 0.017), and a higher sleep fragmentation index (p = 0.041) and average activity (p = 0.0097) during sleep than control subjects. They also had a significantly higher RDI and more severe desaturation during sleep than control subjects (p < 0.01). The differences remained after adjustment for age and BMI but disappeared following adjustment for RDI. CONCLUSIONS: COPD patients with even mild-to-moderate airflow limitations had nocturnal desaturation and RDI-related impaired sleep quality without significant symptoms.

Sleep blood pressure measured using a home blood pressure monitor was independently associated with cardiovascular disease incidence: the Nagahama study.

BACKGROUND: Nocturnal blood pressure (BP) is associated with cardiovascular disease independently of awake BP. However, nocturnal BP measured using an ambulatory monitoring device has limited reproducibility because it is a single-day measurement. We investigated the association between sleep BP measured on multiple days using a timer-equipped home BP monitor and cardiovascular diseases in a general population. METHODS: The study population comprised 5814 community residents. Participants were required to sleep with wrapping cuffs on their upper arm and BP was measured automatically at 0 : 00, 2 : 00, and 4 : 00. Actigraph was used to determine BP measured during sleep. Participants were also measured home morning and evening BP manually using the same device. RESULTS: During the 7.3-year mean follow-up period, we observed 117 cases of cardiovascular diseases. The association between sleep BP (per 10 mmHg hazard ratio = 1.31, P < 0.001) and cardiovascular events remained significant (hazard ratio = 1.22, P = 0.036) even after adjusting for office BP and confounding factors, such as sleep-disordered breathing. Individuals with sleep-only hypertension (n = 1047; hazard ratio = 2.23, P = 0.005) had a significant cardiovascular risk. Daytime-only hypertension (n = 264; hazard ratio = 3.57, P = 0.001) and combined sleep and daytime hypertension (n = 1216; hazard ratio = 3.69, P < 0.001) was associated with cardiovascular events to the same extent. Sleep BP dipping was not identified as a significant determinant of cardiovascular events. CONCLUSION: Sleep BP measured using a home BP monitor was independently associated with the incidence of cardiovascular disease in a general population.

Associations between Nocturnal Hypoxemia and Retinal Nerve Fiber Layer Thinning: The Nagahama Study.

Rationale: There have been meta-analyses that showed reduced retinal nerve fiber layer (RNFL) thickness, which is a surrogate marker of glaucoma, in patients with obstructive sleep apnea (OSA). However, the sample sizes in these reports were small (<300), and the mechanism of RNFL thinning in patients with OSA was not revealed.Objectives: To investigate the relationship of RNFL thickness with nocturnal hypoxemia or hypoxemic burden in a large-scale study.Methods: In this epidemiological study, 8,309 community residents were enrolled. The actigraphy-modified 3% oxygen desaturation index (acti-ODI3%) and cumulative percentage of sleep time with oxygen saturation <90% (acti-CT90) modified by objective sleep duration using actigraphy were measured. The hypoxemic burden is shown as acti-CT90. Circumpapillary RNFL thickness was determined using optical coherence tomography.Results: Multivariable logistic analysis models revealed that an increase in acti-CT90 was significantly associated with mean RNFL thinning after adjusting for several factors in participants without glaucoma diagnosed or treated previously (ß = -0.037; P = 0.009). There were significant differences in mean RNFL thickness among participants stratified according to acti-CT90 (>1.5 vs. ⩽1.5; P = 0.04). Although acti-ODI3% was significantly associated with acti-CT90 (ß = 0.72; P < 0.0001), acti-ODI3% was not significantly associated with mean RNFL thickness in the multivariable logistic analysis (ß = -0.011; P = 0.48). In addition, acti-CT90 was significantly associated with mean RNFL thickness both in the elderly (⩾60 yr; ß = -0.058; P = 0.002) and nonelderly (<60 yr; ß = -0.054; P = 0.007).Conclusions: Acti-CT90, but not acti-ODI3%, was associated with mean RNFL thinning in participants irrespective of age in the elderly or nonelderly. Further prospective studies are required to investigate whether the prevention of hypoxic burden, which was shown as acti-CT90 in this study, is favorable for RNFL thinning.

Diurnal differences in urine flow in healthy young men in a light-controlled environment: a randomized crossover design.

BACKGROUND: Older men often experience nocturnal urination difficulties, reflected by diurnal differences in maximum urine flow (Qmax). Since lower urinary tract symptoms and pathological comorbidities are frequent in older men, it remains unclear whether this diurnal variation is a physiological or pathological phenomenon. Our aim was to quantify the diurnal variability of Qmax in healthy young participants under varying daylight conditions in a stable environment to discern potential underlying causes of nocturnal urination difficulties. METHODS: Twenty-one healthy young men were recruited in a 4-day study utilizing daytime (08:00-18:00) exposure with two light conditions in randomized order: dim (< 50 lx) or bright (~2500 lx). Day 1 was for acclimation, and urine flow was assessed from day 2. The participants urinated ad libitum during day 2 and then at fixed 3-4-h intervals thereafter (days 3-4). Regular urination Qmax at late night (04:00) on day 4 was compared with the nearest voided volume during daytime of day 3 (mDay). RESULTS: Morning Qmax scores (after bed-11:00) on day 2 were significantly lower than evening (17:00-before pre-sleep) in bright conditions and those of daytime (11:00-17:00), evening (17:00-before pre-sleep), and pre-sleep in dim conditions. Pre-sleep Qmax during the ad libitum period was significantly higher in dim than bright conditions. Late-night Qmax values (04:00) on day 4 were significantly lower than Qmax scores of mDay on day 3 in both light conditions. CONCLUSIONS: Healthy young men had a clear diurnal Qmax difference that decreased during late night and morning. In addition, the pre-sleep Qmax values in dim daylight were significantly higher than in bright daylight. Taken together, we conclude that late-night and morning decreases in Qmax are an instinctive physiological phenomenon in humans, and the diurnal difference of Qmax can be influenced by daylight conditions.

Sleep-related factors associated with masked hypertension: the Nagahama study.

OBJECTIVES: Masked hypertension, which is characterized by out-of-office hypertension but normal office blood pressure, is a risk factor for cardiovascular disease. However, the factors that contribute to masked hypertension are unclear. We aimed to determine the involvement of sleep-related characteristics in masked hypertension. METHODS: The study included 3844 normotensive (systolic/diastolic blood pressure < 140/90 mmHg) community residents with no antihypertensive drug use at baseline (mean age 54.3 years). Home morning and evening blood pressure, oxygen desaturation during sleep (pulse oximetry), and sleep efficiency (actigraphy) were measured for 1 week. The number of nocturnal urinations during this period was obtained using a sleep diary. RESULTS: Masked hypertension (mean morning and evening blood pressure ≥135/85 mmHg) was detected in 11.7% of study participants, and 79.0% of the participants with masked hypertension had sleep hypertension (≥120/70 mmHg). Multinominal logistic regression analysis identified different factors involved in masked hypertension with and without sleep hypertension; factors for masked hypertension with sleep hypertension included the frequency of at least 3% oxygen desaturation (coefficient = 0.038, P  = 0.001), nocturia (coefficient = 0.607, P  < 0.001), and carotid intima-media thickness (coefficient = 3.592, P  < 0.001). Only carotid intima-media thickness and measurement season were associated with masked hypertension without sleep hypertension. Low sleep efficiency was associated with isolated sleep hypertension but not masked hypertension. CONCLUSION: Sleep-related factors associated with masked hypertension differed depending on the presence of sleep hypertension. Sleep-disordered breathing and nocturnal urination frequency may help identify individuals who need home blood pressure monitoring.

Associations between Sleep-Disordered Breathing and Serum Uric Acid and Their Sex Differences: The Nagahama Study.

Sleep-disordered breathing (SDB) is often accompanied by noncommunicable diseases (NCDs), including gout. However, the association between serum uric acid (sUA) levels and NCDs is complicated in patients with SDB. We aimed to clarify this issue utilizing large-scale epidemiological data. This community-based study included 9850 inhabitants. SDB and its severity were assessed by a 3% oxygen desaturation index (3% ODI) corrected for sleep duration using wrist actigraphy. The associations between sUA and moderate to severe SDB (MS-SDB) and sUA and NCDs in patients with MS-SDB were analyzed. A total of 7895 subjects were eligible. In females, the prevalence of MS-SDB increased according to an elevation in sUA levels even after adjusting for confounders, and sUA ≥ 5 mg/dL was the threshold. These were not found in males. There was a positive interaction between sUA ≥ 5 mg/dL and female sex for MS-SDB. In females with MS-SDB, the prevalence of diabetes mellitus (DM) increased according to an elevation in sUA levels, and those with sUA ≥ 5 mg/dL showed a higher prevalence of DM than their counterparts. There is a clear correlation between sUA levels and the severity of SDB, and elevated sUA poses a risk for DM in females with MS-SDB.

Hyperfructosemia in sleep disordered breathing: metabolome analysis of Nagahama study.

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (ß = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment.

Differences in relationships among sleep apnoea, glucose level, sleep duration and sleepiness between persons with and without type 2 diabetes.

Obstructive sleep apnoea is common in patients with diabetes. Recently, it was reported that short sleep duration and sleepiness had deleterious effects on glucose metabolism. Thereafter, several reports showed relationships between glucose metabolism and obstructive sleep apnoea, sleep duration or sleepiness. But the interrelationships among those factors based on recent epidemiological data have not been examined. We analysed data on 275 male employees (age, 44±8years; body mass index, 23.9±3.1kg m(-2) ) who underwent a cross-sectional health examination in Japan. We measured fasting plasma glucose, sleep duration using a sleep diary and an actigraph for 7days, and respiratory disturbance index with a type 3 portable monitor for two nights. Fifty-four subjects (19.6%) had impaired glucose metabolism, with 21 having diabetes. Of those 21 (body mass index, 25.9±3.8kgm(-2) ), 17 (81.0%) had obstructive sleep apnoea (respiratory disturbance index≥5). Regarding the severity of obstructive sleep apnoea, 10, four and three had mild, moderate and severe obstructive sleep apnoea, respectively. The prevalence of obstructive sleep apnoea was greater in those with than without diabetes (P=0.037). Multiple regression analyses showed that the respiratory disturbance index independently related to fasting plasma glucose only in the diabetic subjects. In patients with diabetes, after adjustment for age, waist circumference, etc. sleep fragmentation had a greater correlation with fasting plasma glucose than sleep duration, but without significance (P=0.10). Because the prevalence of obstructive sleep apnoea is extremely high in patients with diabetes, sufficient sleep duration with treatment for obstructive sleep apnoea, which ameliorates sleep fragmentation, might improve fasting plasma glucose.

Differences between subjective and objective sleep duration according to actual sleep duration and sleep-disordered breathing: the Nagahama Study.

STUDY OBJECTIVES: Since subjective sleep duration (SSD) is considered to be longer than objective sleep duration (OSD), results of SSD minus OSD (SSD-OSD) might always be thought to be positive. Some recent reports showed different results, but exact results have not been obtained. The difference between SSD and OSD may change according to OSD. We investigated this difference and its association with sleep-disordered breathing (SDB) or nonrestorative sleep. METHODS: This cross-sectional study evaluated 6,908 community residents in Nagahama, Japan. SSD was determined by self-administered questionnaire. OSD was measured by wrist actigraphy and sleep diary. SDB was assessed according to the 3% oxygen desaturation index adjusted for OSD. RESULTS: Worthy of notice was that SSD was shorter than OSD for those with SSD longer than 6.98 hours in all participants, 7.36 hours in males, and 6.80 hours in females. However, SSD was longer than OSD (mean ± SD: 6.49 ± 1.07 vs 6.01 ± 0.96; P < .001) overall, as SSD is considered to be longer than OSD. In patients with SDB, the difference between SSD-OSD was greater when OSD was shorter. The difference also depended on SDB severity. The degree of positivity between OSD and SSD was a significant factor in nonrestorative sleep (odds ratio: 2.691; P < .001). CONCLUSIONS: When OSD was slightly less than 7 (6.98) hours, participants reported or perceived SSD > OSD. When OSD was > 6.98 hours, participants reported or perceived SSD < OSD. Patients with SDB reported longer SSD than OSD according to severity of SDB. Evaluating SSD, OSD, and their differences may be useful for managing sleep disturbances, including nonrestorative sleep. CITATION: Takahashi N, Matsumoto T, Nakatsuka Y, et al. Differences between subjective and objective sleep duration according to actual sleep duration and sleep-disordered breathing: the Nagahama Study. J Clin Sleep Med. 2022;18(3):851-859.

Association of Sleep-disordered Breathing and Blood Pressure with Albuminuria: The Nagahama Study.

Rationale: Although sleep-disordered breathing (SDB) may increase urinary albumin excretion (UAE) by raising nocturnal blood pressure (BP) in addition to diurnal BP, the correlation has not been investigated in a general population. Objectives: To evaluate the relationships among UAE, SDB, and BP during sleep in a large population cohort. Methods: Among 9,850 community residents, UAE was assessed by the urinary albumin-to-creatinine ratio (UACR) in spot urine. Sleep duration and SDB were evaluated by a wearable actigraph and pulse oximeter, respectively. We calculated the actigraphy-modified 3% oxygen desaturation index (Acti-3%ODI) by correcting the time measured by pulse oximetry according to sleep duration obtained by actigraphy. Furthermore, participants were instructed to measure morning and sleep BP at home by a timer-equipped oscillometric device. Results: Measurements of sleep parameters, UAE, and office BP were obtained in 6,568 participants. The multivariate analysis that included confounders showed a significant association of Acti-3%ODI with UACR (ß = 0.06, P < 0.001). Furthermore, a positive interaction between office systolic BP (SBP) and Acti-3%ODI for UACR was found (ß = 0.06, P < 0.001). Among the 6,568 persons enrolled in the analysis, 5,313 completed measurements of BP at home. In this cohort, the association of Acti-3%ODI with UACR remained significant (ß = 0.06, P < 0.001) even after morning and sleep SBP were included in the analysis. Furthermore, a mediation analysis revealed that 28.3% (95% confidence interval, 14.9-41.7%; P < 0.001) of the association of Acti-3%ODI with UACR was explained by the mediation of morning and sleep SBP metrics. Conclusions: SDB and office SBP were independently and synergistically associated with UAE, which is considered a risk factor for chronic kidney disease and cardiovascular events. SDB may raise UAE not only by increasing BP but also by involving other pathologic pathways.

Effects of the presence of hypertension on the relationship between obstructive sleep apnoea and sleepiness.

Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non-sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non-sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle-aged male subjects from a cross-sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects (r = 0.33, P = 0.0024), but not in the 187 non-hypertensive subjects (r = -0.01, P = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further.

Seasonal effects on the continuous positive airway pressure adherence of patients with obstructive sleep apnea.

OBJECTIVE: This study examined seasonal differences in continuous positive airway pressure (CPAP) therapy adherence among patients with obstructive sleep apnea (OSA). METHODS: Patients aged ≥20 years with OSA who had used CPAP devices on the automatic setting for >12 consecutive months (n = 141) were included in this retrospective study from December 2015-2016. The information of CPAP use (pressure, hours of actual use) was extracted from database downloaded from patients' CPAP devices. Patients were divided into adherent and non-adherent groups using the cutoff point of 70% CPAP use for ≥4 h daily over the 1-year study period. CPAP use data were averaged for each season. RESULTS: Patients in the adherent group were significantly older than those in the non-adherent group (p < 0.001). In the adherent group, the rate of ≥4 h daily CPAP use was significantly lower, the daily duration of CPAP use was significantly shorter, and the residual apnea-hypopnea index (AHI; events/hour) was significantly higher in summer than in other seasons (all p < 0.001). In the non-adherent group, the duration of daily CPAP use and the AHI differed significantly between winter and summer (p = 0.008 and p < 0.001, respectively). CONCLUSIONS: Seasonal changes were associated with the CPAP adherence of patients with OSA. The study findings suggest that there is possibility of increasing the duration of CPAP use by adjusting the bedroom environment in hot and humid seasons.

Diurnal rhythms of urine volume and electrolyte excretion in healthy young men under differing intensities of daytime light exposure.

In humans, most renal functions, including urine volume and electrolyte excretions, have a circadian rhythm. Light is a strong circadian entrainment factor and daytime-light exposure is known to affect the circadian rhythm of rectal temperature (RT). The effects of daytime-light exposure on the diurnal rhythm of urinary excretion have yet to be clarified. The aim of this study was to clarify whether and how daytime exposure to bright-light affects urinary excretions. Twenty-one healthy men (21-27 years old) participated in a 4-day study involving daytime (08:00-18:00 h) exposure to two light conditions, Dim (< 50 lx) and Bright (~ 2500 lx), in a random order. During the experiment, RT was measured continuously. Urine samples were collected every 3 ~ 4 h. Compared to the Dim condition, under the Bright condition, the RT nadir time was 45 min earlier (p = 0.017) and sodium (Na), chloride (Cl), and uric acid (UA) excretion and urine volumes were greater (all p < 0.001), from 11:00 h to 13:00 h without a difference in total daily urine volume. The present results suggest that daytime bright light exposure can induce a phase shift advance in urine volume and urinary Na, Cl, and UA excretion rhythms.

Night-time frequency of urination as a manifestation of sleep-disordered breathing: the Nagahama study.

AIMS: Sleep-disordered breathing (SDB) is a well-known risk factor for cardiovascular outcomes. Studies of patients with SDB have identified frequent night-time urination as a manifestation related to SDB. We aimed to clarify whether night-time frequency of urination is independently associated with SDB in a general population. We also investigated whether night-time frequency of urination can help presumptive diagnose SDB. METHODS: Study participants consisted of 7151 community residents. Oxygen saturation during sleep was measured for four nights using a pulse oximeter. SDB was defined as ≥15 events per hour in which oxygen desaturation exceeded or equal to 3% during an actigraphy-determined sleep period. Night-time frequency of urination was recorded for one week using a sleep diary. RESULTS: Significant positive correlations were evident between night-time frequency of urination and SDB (none, 5.8%; once/night, 14.1%; twice/night, 20.1%; thrice/night, 28.7%; >thrice/night, 44.1%, P < 0.001). This association was independent of possible covariates, including sleep duration (adjusted odds ratio: once/night = 1.50, twice/night = 2.15, thrice/night = 3.07, >thrice/night = 3.73, P < 0.001). Other factors significantly associated with SDB were age, sex, obesity, observation of sleep apnea, and short sleep duration. The area under the curve of the risk score for SDB consisting of these conventional six items (0.834) significantly improved (0.842, P = 0.001) when night-time frequency of urination was considered as a risk score item. CONCLUSION: Night-time frequency of urination was associated with SDB. Our findings suggest that the urination frequency should be considered a manifestation of SDB even in a general population.

Markers of cardiovascular disease risk in sleep-disordered breathing with or without comorbidities: the Nagahama study.

STUDY OBJECTIVES: Whether the association between sleep-disordered breathing (SDB) and cardiovascular disease is independent of comorbid risk factors for cardiovascular disease is controversial. The objective of this study was to elucidate whether the association between SDB severity and the surrogate markers of cardiovascular disease events differs in relation to the number of comorbidities. METHODS: This cross-sectional study included 7,731 participants. Severity of SDB was determined by the oxygen desaturation index adjusted by actigraph-measured objective sleep time. Participants were stratified according to SDB severity and the number of comorbidities (hypertension, diabetes, dyslipidemia, and obesity), and the associations between the maximum value of intima-media thickness of the common carotid artery (CCA-IMT-max), brachial-ankle pulse wave velocity, and cardio-ankle vascular index were evaluated. RESULTS: Among participants with no risk factors, CCA-IMT-max increased according to SDB severity (n = 1022, P < .0001). Even after matching the background, the median CCA-IMT-max value was 14% higher in moderate-severe SDB patients than those without SDB (n = 45 in each group, P = .020). The difference was not significant for brachial-ankle pulse wave velocity and cardio-ankle vascular index. On the other hand, a significant difference in CCA-IMT-max was not found in those with multiple comorbidities. Consistently, multiple regression analysis revealed an independent association between CCA-IMT-max and moderate-severe SDB for all study participants (ß: 0.0222, 95% confidence interval: 0.0039-0.0405, P = .017), but the association was not significant for stratified participants with multiple comorbidities. CONCLUSIONS: SDB severity is associated with the CCA-IMT-max level, but the independent association becomes weaker for those with multiple comorbidities. CITATION: Nakatsuka Y, Murase K, Matsumoto T, et al. Markers of cardiovascular disease risk in sleep-disordered breathing with or without comorbidities: the Nagahama Study. J Clin Sleep Med. 2021;17(12):2467-2475.

Impact of sleep-disordered breathing on glucose metabolism among individuals with a family history of diabetes: the Nagahama study.

STUDY OBJECTIVES: It is well known that a family history of diabetes (FHD) is a definitive risk factor for type 2 diabetes. It has not been known whether sleep-disordered breathing (SDB) increases the prevalence of diabetes in those with an FHD. METHODS: We assessed SDB severity in 7,477 study participants by oximetry corrected by objective sleep duration determined by wrist actigraphy. Glycated hemoglobin ≥6.5% and/or current medication for diabetes indicated the presence of diabetes. In addition to the overall prevalence, the prevalence of recent-onset diabetes during the nearly 5 years before the SDB measurements were made was investigated. RESULTS: Of the 7,477 participants (mean age: 57.9; range: 34.2-80.7; SD: 12.1 years; 67.7% females), 1,569 had an FHD. The prevalence of diabetes in FHD participants with moderate-to-severe SDB (MS-SDB) was higher than in those without SDB (MS-SDB vs without SDB: all, 29.3% vs 3.3% [P < .001]; females, 32.6% vs 1.9% [P < .001]; males, 26.2% vs 11.7% [P = .037]). However, multivariate analysis showed that MS-SDB was significantly associated with a higher prevalence of diabetes only in FHD-positive females (odds ratio [95% confidence interval]: females, 7.43 [3.16-17.45]; males, 0.92 [0.37-2.31]). Among the FHD-positive participants, the prevalence of recent-onset diabetes was higher in those with MS-SDB than those without SDB, but only in females (MS-SDB vs without SDB: 21.4% vs 1.1%; P < 0.001). CONCLUSIONS: MS-SDB was associated with diabetes risk in females with an FHD, and future studies are needed on whether treatment of SDB in females with an FHD would prevent the onset of diabetes.