Longitudinal association of sleep-disordered breathing and nondipping of nocturnal blood pressure in the Wisconsin Sleep Cohort Study

STUDY OBJECTIVES: The association of sleep-disordered breathing (SDB) and blunting of normal nocturnal lowering of blood pressure (BP) (nondipping) has only been examined cross-sectionally. The purpose of this study is to investigate whether SDB is prospectively associated with nondipping. METHODS: The longitudinal association between SDB and incident nondipping was examined in a subsample of 328 adults enrolled in the Wisconsin Sleep Cohort Study who completed 2 or more 24-hour ambulatory BP studies over an average of 7.2 years of follow-up. SDB identified by baseline in-laboratory polysomnography was defined by apnea-hypopnea index (AHI) categories. Systolic and diastolic nondipping was defined by systolic and diastolic sleep-wake BP ratios > 0.9. All models were adjusted for age, sex, body mass index at baseline and follow-up, smoking, alcohol consumption, hypertension, sleep time, length of follow-up time, and antihypertensive medication use. RESULTS: There was a dose-response increased odds of developing systolic nondipping in participants with SDB. The adjusted odds ratios (95% confidence interval) of incident systolic nondipping for baseline AHI 5 to < 15 and AHI > or = 15, versus AHI < 5, were 3.1 (1.3-7.7) and 4.4 (1.2-16.3), respectively (P trend = 0.006). The adjusted odds ratios (95% confidence interval) of incident diastolic nondipping for corresponding SDB categories were not statistically significant: 2.0 (0.8-5.6) and 1.3 (0.2-7.1). CONCLUSIONS: Our longitudinal findings of a dose-response increase in development of systolic nondipping of BP with severity of SDB at baseline in a population-based sample provide evidence consistent with a causal link. Nocturnal systolic nondipping may be a mechanism by which SDB contributes to increased cardiovascular disease.     

Prospective study of the association between sleep-disordered breathing and hypertension

BACKGROUND: Sleep-disordered breathing is prevalent in the general population and has been linked to chronically elevated blood pressure in cross-sectional epidemiologic studies. We performed a prospective, population-based study of the association between objectively measured sleep-disordered breathing and hypertension (defined as a laboratory-measured blood pressure of at least 140/90 mm Hg or the use of antihypertensive medications). METHODS: We analyzed data on sleep-disordered breathing, blood pressure, habitus, and health history at base line and after four years of follow-up in 709 participants of the Wisconsin Sleep Cohort Study (and after eight years of follow-up in the case of 184 of these participants). Participants were assessed overnight by 18-channel polysomnography for sleep-disordered breathing, as defined by the apnea-hypopnea index (the number of episodes of apnea and hypopnea per hour of sleep). The odds ratios for the presence of hypertension at the four-year follow-up study according to the apnea-hypopnea index at base line were estimated after adjustment for base-line hypertension status, body-mass index, neck and waist circumference, age, sex, and weekly use of alcohol and cigarettes. RESULTS: Relative to the reference category of an apnea-hypopnea index of 0 events per hour at base line, the odds ratios for the presence of hypertension at follow-up were 1.42 (95 percent confidence interval, 1.13 to 1.78) with an apnea-hypopnea index of 0.1 to 4.9 events per hour at base line as compared with none, 2.03 (95 percent confidence interval, 1.29 to 3.17) with an apnea-hypopnea index of 5.0 to 14.9 events per hour, and 2.89 (95 percent confidence interval, 1.46 to 5.64) with an apnea-hypopnea index of 15.0 or more events per hour. CONCLUSIONS: We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.     

Sleep pressure score: a new index of sleep disruption in snoring children

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS), as measured by objective criteria, is infrequent in snoring children despite a high prevalence of EDS-related behavioral manifestations. We hypothesized that sleep architecture and arousal indexes may be altered relative to the severity of sleep-disordered breathing (SDB). DESIGN: Retrospective and prospective study. SETTING: Questionnaires were distributed through sleep clinic or school program; polysomnograms were performed at Kosair Children's Hospital in Louisville, Kentucky. PARTICIPANTS: To examine this issue, 182 children with SDB, 163 children with primary snoring, and 214 control children with a mean age of 6.9 +/- 2.6 years underwent polysomnographic evaluation in the laboratory. MEASUREMENTS AND RESULTS: Significant increases in slow-wave sleep (percentage of total sleep time) and decreases in rapid eye movement sleep (percentage of total sleep time) occurred in the SDB group (P < .0001). Spontaneous and respiratory arousal indexes and the apnea-hypopnea index (AHI) displayed negative and positive correlations, respectively, suggesting reciprocal interactions. Based on these observations, a sleep pressure score (SPS) was derived as a surrogate numeric measure for disrupted sleep homeostasis. The SPS exhibited linear increases relative to AHI, reaching a plateau at an AHI of 30 to 40 per hour of total sleep time. Furthermore, SPS values were significantly higher among African American and obese children (P < .0001). CONCLUSIONS: Sleep architecture is not preserved in children with SDB. An algorithm allowing for calculation of sleep propensity and disturbed sleep homeostasis in children who snore is proposed and may be of practical value in the assessment of sleepiness.     

The effects of hormone replacement therapy on sleep-disordered breathing in postmenopausal women: a pilot study

STUDY OBJECTIVES: To evaluate the impact of estrogen and estrogen plus progesterone hormone-replacement therapy (HRT) on mild-to-moderate sleep-disordered breathing (SDB) in postmenopausal women. DESIGN AND SETTING: Within-subjects, progesterone placebo-controlled prospective HRT trial in a clinical laboratory. PARTICIPANTS: Six postmenopausal women, diagnosed with mild-moderate SDB. INTERVENTION: Transdermal estradiol and oral micronized progesterone. MEASUREMENTS AND RESULTS: Subjects underwent polysomnography (PSG) on four occasions: a screening/adaptation night; a baseline night on no HRT; and two nights on HRT: one night after 7 to 12 days on estrogen plus placebo followed by a second night after 7-13 days on estrogen plus progesterone. The PSG was performed with a Sandman computerized PSG system using a standard clinical montage. Modified sleep diaries were used in the baseline week and throughout the study period. Mood was measured with the 20-item version of the Positive and Negalive Affect Schedule (PANAS). Estrogen monotherapy was associated with a significant reduction in the overall apnea-hypopnea index (AHI) (from a mean of 22.7 events per hour at baseline to a mean of 12.2 events per hour), but the AHI reduction on estradiol plus progesterone relative to baseline was not statistically significant (AHI=16.2 events per hour). Similar results were found for the percentages of total sleep time and of total non-rapid eye movement sleep time with oxygen saturation less than 90%. Estrogen, neither alone nor in combination with progesterone, significantly altered PSG- or diary-based measures of total sleep time, time to sleep onset, or time awake after sleep onset. CONCLUSIONS: While the data are preliminary and based on a small number of subjects, estrogen appeared to have a substantial beneficial effect on measures of SDB in postmenopausal women. Overall, no additional benefit was seen with the addition of progesterone. In fact, progesterone attenuated the beneficial effects of estrogen in 4 out of the 6 participants.     

Children with obstructive sleep-disordered breathing generate high-frequency inspiratory sounds during sleep

STUDY OBJECTIVES: We observed that some children with adenotonsillar hypertrophy and obstructive sleep-disordered breathing (SDB) make high-frequency inspiratory sounds (HFIS) during sleep. Our objective was to determine whether HFIS occur in most children with obstructive SDB and adenotonsillar hypertrophy and whether adenotonsillectomy reduces HFIS. DESIGN: Prospective consecutive-entry trial. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-six children between 6 and 12 years of age with adenotonsillar hypertrophy suspected of having obstructive SDB. MEASUREMENTS AND RESULTS: We performed polysomnography and measured sounds during sleep with a microphone suspended above the bed. Sounds were recorded on a computer at 44 kHz, analyzed with fast Fourier transformation for frequency content. HFIS were sounds occurring during an inspiration with frequencies greater than 2 kHz. HFIS were different from the low-frequency (< 2 kHz) sounds described in snoring adults. HFIS usually occurred in consecutive breaths, occasionally exceeding 100. We counted the number of HFIS that occurred per hour of sleep. Children who made more HFIS had more obstructive SDB than did those who did not make the HFIS, and there was a significant positive correlation between the number of HFIS and the obstructive apnea-hypopnea index. Children with more than 3 apneas and hypopneas per hour of sleep all made at least 10 HFIS per hour, and all children who had more than 10 HFIS per hour had obstructive apnea-hypopnea index values greater than 1. Children with adenotonsillar hypertrophy made more HFIS than did those children whose tonsils and adenoids had been removed. CONCLUSIONS: HFIS may be a marker of disturbed breathing during sleep in children with adenotonsillar hypertrophy.     

Sleep-disordered breathing and its concomitants in a subclinical population

In order to evaluate possible deficits accompanying sleep-disordered breathing (SDB) in a subclinical population, the nocturnal respiration, health status, and sleep/wake cycle of 46 healthy, heavy-snoring men were measured. Sixty-two percent of these subjects had at least one episode of apnea/hypopnea, while 13% had high levels of apnea/hypopnea [apnea/hypopnea index (AHI) greater than or equal to 5]. Most events occurred in stages 1 or 2 or in REM sleep. Strong relationships between weight and SDB were observed, as were more modest relationships between age and SDB. Correlational procedures indicated relationships between SDB and higher blood pressure, subjective sleepiness, and napping. Because similar, but stronger, relationships involving these variables are observed in patients with a sleep apnea syndrome (SAS), it appears that a continuum exists between heavy-snoring men and patients with SAS. When these subjects were grouped by level of SDB, subjects with high levels of SDB (AHI greater than or equal to 5) had significantly lower nocturnal oxygenation parameters than the remaining subjects. However, there were no between-group differences in health or sleep/wake variables. It is concluded that while apnea/hypopnea events in subclinical populations may not be completely benign events, the level at which they may be considered frankly pathological is presently unclear.     

Severity of sleep-disordered breathing improves following parturition

STUDY OBJECTIVE: Changes in sleep-disordered breathing associated with late pregnancy have not previously been systematically investigated; however, a number of case reports indicate exacerbation of obstructive sleep apnea in late pregnancy, often in association with maternal hypertension. We aimed to compare the severity of sleep-disordered breathing and associated maternal blood-pressure responses in late pregnancy with the nonpregnant state. DESIGN: Case-controlled, longitudinal study of sleep-disordered breathing during late pregnancy and postpartum. Study Patients: Ten women referred for suspected sleep-disordered breathing during the third trimester of pregnancy. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Full overnight polysomnography and continuous systemic blood pressure were measured during the third trimester of pregnancy and 3 months following delivery. Parameters of sleep-disordered breathing, including apnea hypopnea index and minimum overnight arterial oxyhemoglobin saturation, were compared between antenatal and postnatal studies. An improvement in both apnea-hypopnea index and minimum arterial oxyhemoglobin saturation occurred consistently in all subjects postnatally. In non-rapid eye movement sleep, mean apnea-hypopnea index was reduced from 63 +/- 15 per hour antenatally to 18 +/- 4 per hour postnatally (P = .03), and in rapid eye movement sleep, from 64 +/- 11 per hour to 22 +/- 4 per hour (P = .002). Minimum arterial oxyhemoglobin saturation was increased from 86% +/- 2% antenatally to 91% +/- 1% postnatally (P = .01). Arterial blood-pressure responses to apnea peaked at 170 to 180 mm Hg antenatally, while they only peaked at 130 to 140 mm Hg postnatally. CONCLUSION: This study indicates that late pregnancy may be associated with increased severity of sleep-disordered breathing and associated blood-pressure responses.     

Sleep Disordered Breathing and Hypertension: Does Self-Reported Sleepiness Modify the Association?

STUDY OBJECTIVES: Epidemiologic studies that demonstrate increased risk of hypertension in persons with sleep disordered breathing indicate that only a minority of these persons report significant subjective sleepiness. Studies also suggest that presence of self-reported sleepiness may identify a subset of persons with sleep disordered breathing who are at greatest risk of cardiovascular sequelae, including hypertension. We explore whether self-reported sleepiness modifies the relationship between sleep disordered breathing and prevalent hypertension. DESIGN: Cross-sectional. SETTING: Multicenter study. PARTICIPANTS: 6046 subjects from the Sleep Heart Health Study. MEASUREMENTS: Polysomnography, systolic and diastolic blood pressure, antihypertensive medication use, questionnaire determined excessive sleepiness and Epworth Sleepiness Scale, and covariates. RESULTS: The odds of hypertension at higher apnea hypopnea index categories were larger in participants identified as sleepy based on responses to a frequency of sleepiness question or the Epworth score. For example, for those with AHI > or =30 compared to AHI <1.5, the adjusted odds ratio for hypertension was 2.83 (1.33-6.04) among those reporting sleepiness > or =5 days per month, but only 1.22 (0.89-1.68) among those reporting less frequent daytime sleepiness. In adjusted logistic regression models, there was statistical evidence for effect modification by frequency of sleepiness (P = 0.033) of the association between apnea hypopnea index and hypertension. In adjusted models that included the Epworth score as a continuous variable, the interaction term fell slightly short of statistical significance (beta = 0.010, P = 0.07). CONCLUSION: This study finds that the association of sleep disordered breathing with hypertension is stronger in individuals who report daytime sleepiness than in those who do not.     

The Effects of Sleep-Disordered Breathing on Arterial Stiffness are Modulated by Age

Study Objectives:

To identify associations between sleep-disordered breathing (SDB) and arterial stiffness.

Setting:

Nested cross-sectional study.

Participants:

One hundred fifty-three participants (ages 45-77 years, 43% women) in the population-based Wisconsin Sleep Cohort. Eighty-three had SDB and were not using continuous positive airway pressure therapy.

Interventions:

Measurement of aortic pulse wave velocity (PWV) by arterial tonometry. Nocturnal polysomnography.

Measurements and Results:

SDB was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hour of sleep. By study design those with SDB had higher mean (SD) AHI (17.6 [16.2] vs 2.2 [1.3] events/h), as well as lower average nocturnal O₂ saturation (91.5 [2.1] vs 93.0 [1.4] %, P < 0.001) and larger waist circumference (102.5 [13.2] vs 92.5 [12.5] cm, P < 0.001), but they had similar central aortic systolic (122.8 [15.1] vs 119.1 [11.8] mm Hg, P = 0.100) and diastolic blood pressures (77.1 [9.4] vs 77.4 [8.6] mm Hg, P = 0.834), and PWV (9.06 [2.15] vs 8.51 [1.88] m/s; all P > 0.10). Markers of SDB that were correlated with PWV were nocturnal O₂saturation (r = −0.24, P = 0.004) and AHI (r = 0.18, P = 0.032); however, these associations were not statistically significant after adjustment. In subjects not on antihypertensive medications, a significant interaction between nocturnal O₂ saturation and age was identified (β = −0.019, P = 0.039), such that the effect of nocturnal oxygen O₂ on PWV increased with age (adjusted R² = 0.468).

Conclusions:

Adverse effects of nocturnal oxygen desaturation on PWV are seen among normotensive individuals and are amplified with aging. Integrated assessment of SDB is necessary to characterize its effects on arterial stiffness.

Citation:

Korcarz CE; Gepner AD; Peppard PE; Young TB; Stein JH. The effects of sleep-disordered breathing on arterial stiffness are modulated by age. SLEEP 2010;33(8):1081-1085.     

Sleep-disordered breathing and white matter disease in the brainstem in older adults

STUDY OBJECTIVES: To examine whether sleep-disordered breathing is associated with white matter disease in the brainstem. DESIGN: A population-based longitudinal study. SETTING: Allegheny County, PA; Sacramento County, CA; and Washington County, MD. PATIENTS OR PARTICIPANTS: A total of 789 individuals, aged 68 years or older, drawn from the Sleep Heart Health Study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The participants underwent home polysomnography in 1995-1998 and cerebral magnetic resonance imaging in both 1992-1993 and 1997-1998. The apnea-hypopnea index was not associated with white matter disease in the brainstem, with or without adjusting for age, sex, race, community, body mass index, smoking status, alcohol use, systolic blood pressure, and the use of antihypertensive medication. In contrast, the arousal index (number of arousals per hour of sleep) was inversely associated with brainstem white matter disease (odds ratio = 0.75 for a SD increase in the arousal index, 95% confidence interval: 0.62, 0.92). CONCLUSIONS: The frequency of apneas and hypopneas was not associated with brainstem white matter disease in these older adults. A unique relationship with arousal frequency suggests that ischemic changes in the brainstem may be associated with arousals during sleep.     

Sex influences endothelial function in sleep-disordered breathing

BACKGROUND: The bases for the association between sleep-disordered breathing (SDB) and cardiovascular disease are poorly understood. Endothelial dysfunction, assessed with brachial artery ultrasonography, may predict cardiovascular risk and represent preclinical vascular disease. We determined whether flow-mediated dilation (FMD) and peak blood flow (PBF) increase after cuff occlusion is altered with SDB. METHODS: 193 participants (58% women) in a cohort study were studied with overnight polysomnography and subsequent brachial artery ultrasonography. SDB was quantified using the apnea-hypopnea index (AHI) and indexes of overnight desaturation and arousal frequency. Two-dimensional and Doppler-velocity measurements of the brachial artery were obtained at baseline and after 5 minutes of upper-arm cuff occlusion. FMD and PBF were defined as the percentage changes from baseline in brachial artery diameter and flow, respectively. RESULTS: In the entire sample, the AHI was inversely associated with both FMD (r = -0.30, P < .001) and PBF (r = -0.20, P < .001). However, sex-stratified univariate analyses showed that these relationships were exclusive to women. Specifically, FMD was significantly lower in women with an AHI > or = 15 than in women with lower AHI scores (P < .005), with no relationship between AHI and FMD in men. Additionally, PBF decreased significantly with increasing AHI (r = -0.29, P = .010) in women alone. Statistical modeling, adjusting for body mass index, age, and other covariates, similarly showed that SDB severity significantly influenced FMD and PBF, with significant interactions between sex and AHI, reinforcing that the associations between SDB severity and endothelial function were stronger in women than in men. CONCLUSIONS: Moderate levels of SBD are associated with impaired conduit and resistance endothelial function in women. Women with SDB may be more vulnerable to early SDB-related cardiovascular disease than are men.     

Hyperactivity and polysomnographic findings in children evaluated for sleep-disordered breathing

STUDY OBJECTIVES: Children with sleep-disordered breathing (SDB) or periodic leg movements during sleep (PLMS) often have hyperactive behavior that improves when the sleep disorder is treated. Some children with SDB also have PLMS. To determine what polysomnographic features of SDB might be associated with hyperactive behavior, we studied behavior, SDB, and PLMS in a series of patients. DESIGN: Prospective and observational. SETTING: University-based sleep disorders laboratory. SUBJECTS: Children (n=113) aged 2 to 18 years, referred for suspected SDB. INTERVENTIONS: Parents completed the hyperactivity index of the Connors' Parental Rating Scale, and results were converted to age-adjusted t-scores. Children underwent laboratory-based polysomnography, with esophageal pressure monitoring when requested (n=19) by referring physicians. RESULTS: Children with SDB (n=59) showed high hyperactivity scores (mean 59.5+/-18.3 SD, 95% C.I. [54.7, 64.2]) but these scores were no higher than those of children without SDB (59.0+/-15.1, [54.8, 63.1]). Hyperactivity showed no significant associations with the rate of apneas and hypopneas, minimum oxygen saturation, or most negative esophageal pressure (p>0.10), but was associated with the presence of 5 or more PLMS per hour (p=0.02). The rate of PLMS showed a linear association with hyperactivity among those subjects with SDB (p = 0.002), but no association among those subjects without SDB (p = 0.64). CONCLUSIONS: These findings suggest that hyperactive behavior is common among children referred for suspected SDB, regardless of the presence or severity of SDB. Current observations cannot prove causality, but they are consistent with the hypothesis that PLMS may contribute to hyperactivity and SDB may act as an effect modifier.     

Sleep-disordered breathing in a predominantly African-American pediatric population

The goal of this study was to characterize sleep and respiratory parameters in children with sleep-disordered breathing (SDB) as compared to children without SDB. Data are from 198 children and adolescents referred for sleep center evaluation, 128 of whom were diagnosed with SDB. In children with SDB, obesity (> 95% wgt for age) was more common than being severely underweight (< 5% wgt for age), but only the older children with SDB were heavier than age-matched normal sleepers. Children with SDB had increased EEG arousals; sleep architecture was not otherwise significantly different from the non-SDB group. African-American children with SDB had significantly greater oxygen desaturation with obstructive events compared to Caucasian and Latino children. It appears that the role of obesity as a risk factor for obstructive sleep apnea (OSA) increases in children above the age of 8-years. Additionally, African-American children with SDB may be at increased risk for hypoxemia and cardiovascular consequences of SDB.     

Exercise and sleep-disordered breathing: an association independent of body habitus

STUDY OBJECTIVES: The degree to which physical exercise habits are related to sleep-disordered breathing is not known. We sought to investigate the association between a single-item exercise question and laboratory-assessed sleep-disordered breathing. DESIGN: A population-based cross-sectional epidemiologic study of adults measured the association between exercise and sleep-disordered breathing. Hours of weekly planned exercise were assessed by questionnaire. Sleep-disordered breathing was assessed by 18-channel in-laboratory polysomnography and characterized by the apnea-hypopnea index. SETTING: Polysomnography was conducted at the University of Wisconsin General Clinical Research Center sleep laboratory. PATIENTS AND PARTICIPANTS: Participants included 1104 men and women, aged 30 to 60 years, enrolled in the Wisconsin Sleep Cohort Study. MEASUREMENTS AND RESULTS: Associations were modeled using linear and logistic regression, adjusting for body mass index, skinfold measurements, age, sex, and other covariates. Adjusted mean (95% confidence interval) apnea-hypopnea index was 5.3 (4.4, 6.2) events per hour for participants who exercised 0 hours per week; 3.9 (2.8, 5.0) events per hour for those with 1 to 2 hours of exercise; 3.2 (2.2, 4.2) events per hour for those with 3 to 6 hours of exercise; and 2.8 (1.0, 4.6) for those with > 7 hours of exercise (P trend < .001). Similarly, the odds of having moderate or worse sleep-disordered breathing (apnea-hypopnea index > 15 events per hour) significantly decreased with increasing level of exercise. CONCLUSION: Independent of measures of body habitus, lack of exercise was associated with increased severity of sleep-disordered breathing.     

Association of usual sleep duration with hypertension: the Sleep Heart Health Study

STUDY OBJECTIVES: Limited experimental data suggest that sleep restriction acutely elevates blood pressure; however, little is known about the relationship between usual sleep duration and hypertension. This study assesses the relationship between usual sleep duration and hypertension in a community-based cohort. DESIGN: Cross-sectional observational study. SETTING: The Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. PARTICIPANTS: Two thousand eight hundred thirteen men and 3097 women, aged 40 to 100 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Usual weekday and weekend sleep durations were obtained by questionnaire, and their weighted average were categorized as less than 6, 6 to less than 7, 7 to less than 8, 8 to less than 9, and 9 or more hours per night. Hypertension was defined as a systolic blood pressure of 140 mm Hg or greater, a diastolic blood pressure of 90 mm Hg or greater, or use of medication to treat hypertension. The relationship between sleep duration and hypertension was examined using categorical logistic regression with adjustment for age, sex, race, apnea-hypopnea index, and body mass index. Compared to subjects sleeping 7 to less than 8 hours per night, those sleeping less than 6 and between 6 and 7 hours per night had adjusted odds ratios for hypertension of 1.66 (95% confidence interval 1.35-2.04) and 1.19 (1.02-1.39), respectively, whereas those sleeping between 8 and 9 and 9 or more hours per night had adjusted odds ratios for hypertension of 1.19 (1.04-1.37) and 1.30 (1.04-1.62), respectively (p < .0001 for association of sleep duration with hypertension). These associations persisted when analyses were further adjusted for caffeine and alcohol consumption, current smoking, insomnia symptoms, depression symptoms, sleep efficiency, and prevalent diabetes mellitus or cardiovascular disease. CONCLUSIONS: Usual sleep duration above or below the median of 7 to less than 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night.     

The relationship between sleep-disordered breathing and high-sensitivity C-reactive protein in Japanese men

STUDY OBJECTIVES: Elevated C-reactive protein (CRP), an inflammatory marker and emerging risk factor for atherosclerosis and coronary heart disease, has been reported in overweight patients with sleep-disordered breathing (SDB). However, the contribution of C-reactive protein to this disease among non-overweight individuals is uncertain. We thus examined the relationship between serum C-reactive protein levels and nocturnal arterial oxygen desaturation, stratified by category of body mass index (BMI). DESIGN: Cross-sectional study. PARTICIPANTS: Subjects were 316 men with a mean BMI of 25.4 kg/m2, aged 20-79 years, who attended a sleep clinic at Osaka, Japan. MEASUREMENTS AND RESULTS: SDB was assessed by oxygen desaturation index (ODI) measured by pulse oximetry during sleep. We used 3% oxygen desaturations per hour (3% ODI), as the indicator of SDB. We also measured serum levels of C-reactive protein (CRP). After adjustment for age, BMI, hypertension, diabetes mellitus, hypercholesterolemia, smoking status, alcohol consumption, and daily sleep duration, mean high-sensitivity CRP levels were 0.63, 0.65, and 0.96 mg/L for SDB severity levels of 3%ODI<5, 5 to 19.9, and >=20, respectively (p for trend=0.015). This association with SDB tended to be stronger in non-overweight men (BMI<25 kg/m2) (0.47, 0.48 and 1.02 mg/L, p for trend=0.017) than in overweight men (BMI > or = 25 kg/m2) (0.92, 0.87 and 1.21 mg/L, p for trend=0.11). CONCLUSION: SDB is associated with increased levels of CRP, especially in non-overweight men. Our results suggest the importance of follow-up and control of SDB in the prevention of cardiovascular disease even in non-overweight SDB patients.     

Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing

OBJECTIVES: To assess the efficacy of added carbon dioxide as adjunctive therapy to positive airway pressure-refractory mixed obstructive and central sleep-disordered breathing, using a prototype device-the positive airway pressure gas modulator. DESIGN: Open-label evaluation of low concentrations of carbon dioxide added to a positive airway pressure circuit. SETTING: Physician-attended polysomnographic titration in a free-standing sleep laboratory with end-tidal and transcutaneous carbon-dioxide monitoring. PATIENTS: Six adult men (age 54 +/- 5.7 years) with severe poorly controlled mixed sleep-disordered breathing in the absence of renal or heart failure. INTERVENTIONS: Flow-independent addition of incremental concentrations of carbon dioxide during sleep. MEASUREMENTS AND RESULTS: The respiratory disturbance index before treatment was 66 +/- 14.5 events per hour of sleep, with a nocturnal desaturation low of 84.6% +/- 10.1%. Residual respiratory disturbance index on best treatment was 43 +/- 9 events per hour of sleep. There was an immediate (<1 minute) response to the addition of 0.5% to 1% carbon dioxide, and minimal changes were required to be made across the night. There was no discomfort, shortness of breath, palpitations, headache, or significant increase in respiratory or heart rate. The residual respiratory disturbance index on carbon dioxide, scored irrespective of desaturations, was in the normal range (< 5 / hour of sleep). Two subjects had a second night at the concentration of carbon dioxide determined to be efficacious, with no required concentration change. No adverse effects on overall sleep architecture were noted. CONCLUSIONS: Low concentrations of carbon dioxide added to conventional positive airway pressure effectively control severe treatment-resistant mixed obstructive and central sleep-disordered breathing.     

The relationship between chronically disrupted sleep and healthcare use

STUDY OBJECTIVES: To determine whether chronic sleep deprivation, sleep disruption, sleepiness, insomnia, and OSA are associated with increased healthcare use in a community-based population. DESIGN: Cross-sectional study. SETTING/PARTICIPANTS: 6440 Sleep Heart Health Study (SHHS) participants recruited from ongoing cohort studies. Interventions: N/A MEASUREMENTS: Polysomnography results (Apnea Hypopnea Index (AHI), percent of sleep time with oxyhemoglobin saturation below 90% (CT90), arousal index) as well as data on sleep related symptoms, medication use, and chronic illness. The indirect measure of predicted healthcare utilization was the modified Chronic Disease Score (CDS) calculated from medication data. RESULTS: After adjustment for age, gender, BMI and study site, subjects in the highest quartiles of AHI, CT90 and Epworth score had CDS that were 6%-9% higher than the lowest quartiles. The adjusted mean CDS for subjects with sleep apnea was similar to that for subjects with hypertension, chronic bronchitis or asthma and 18% greater than the mean CDS for subjects without sleep apnea. Among subjects who did not have significant sleep-disordered breathing, complaints of insomnia, sleepiness, fatigue, and not getting enough sleep were associated with increased CDS. CONCLUSIONS: This study demonstrated an association between subjective complaints of daytime sleepiness, inadequate sleep time, insomnia as well as objective measures of severity of SDB, and an indirect measure of healthcare utilization in a community-based sample. Though the percent increases in healthcare utilization observed were modest, the prevalence of these factors in the general population is high, and may therefore be associated with a substantial cost burden to the healthcare system.     

Behavioral Correlates of Sleep-Disordered Breathing in Older Men

Study Objectives:

To examine the association between sleep-disordered breathing (SDB) and subjective measures of daytime sleepiness, sleep quality, and sleep-related quality of life in a large cohort of community-dwelling older men and to determine whether any association remained after adjustment for sleep duration.

Design:

Cross-sectional. The functional outcome measures of interest were daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep-related symptoms (Pittsburgh Sleep Quality Index, PSQI), and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire, FOSQ). Analysis of variance and adjusted regression analyses examined the association between these outcome measures and SDB severity and actigraphy-determined total sleep time (TST). We then explored whether associations with SDB were confounded by sleep duration by adjusting models for TST.

Setting:

Community-based sample in home and research clinic settings.

Participants:

Two-thousand eight-hundred forty-nine older men from the multicenter Osteoporotic Fractures in Men Study that began in 2000. All participants underwent in-home polysomnography for 1 night and wrist actigraphy for a minimum of 5 consecutive nights.

Interventions:

N/A.

Measurements and Results:

Participants were aged 76.4 ± 5.5 years and had an apnea-hypopnea index (AHI) of 17.0 ± 15.0. AHI and TST were weakly correlated. ESS scores individually were modestly associated with AHI and TST, but the association with AHI was attenuated by adjustment for TST. PSQI and FOSQ scores were largely not associated with measures of SDB severity but were modestly associated with TST.

Conclusions:

Daytime sleepiness, nighttime sleep disturbances, and sleep-related quality of life were modestly associated with TST. After adjustment for TST, there was no independent association with SDB severity. These results underscore the potential differences in SDB functional outcomes in older versus young and middle-aged adults.

Citation:

Kezirian EJ; Harrison SL; Ancoli-Israel S; Redline S; Ensrud K; Goldberg AN; Claman DM; Spira AP; Stone KL. Behavioral correlates of sleep-disordered breathing in older men. SLEEP 2009;32(2):253–261.     

Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study

Epidemiologic literature suggests that persons with clinically diagnosed sleep apnoea frequently have impaired cognitive function, but whether milder degrees of sleep-disordered breathing (SDB) are associated with cognitive dysfunction in the general population is largely unknown. Approximately 1700 subjects free of clinically diagnosed SDB underwent at-home polysomnography (PSG) as part of the Sleep Heart Health Study (SHHS) and completed three cognitive function tests within 1-2 years of their PSG: the Delayed Word Recall Test (DWR), the WAIS-R Digit Symbol Subtest (DSS), and the Word Fluency test (WF). A respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. After adjustment for age, education, occupation, field centre, diabetes, hypertension, body-mass index, use of CNS medications, and alcohol drinking status, there was no consistent association between the RDI and any of the three cognitive function measures. There was no evidence of a dose-response relation between the RDI and cognitive function scores and the adjusted mean scores by quartiles of RDI never differed from one another by more than 5% for any of the tests. In this sample of free-living individuals with mostly mild to moderate levels of SDB, the degree of SDB appeared to be unrelated to three measures of cognitive performance.