Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension

OBJECTIVE: Obstructive sleep apnea (OSA) and primary aldosteronism are common in subjects with resistant hypertension; it is unknown, however, if the two disorders are causally related. This study relates plasma aldosterone and renin levels to OSA severity in subjects with resistant hypertension, and in those with equally severe OSA but without resistant hypertension serving as control subjects. METHODS: Seventy-one consecutive subjects referred to the University of Alabama at Birmingham (UAB) for resistant hypertension (BP uncontrolled on three medications) and 29 control subjects referred to UAB Sleep Disorders Center for suspected OSA were prospectively evaluated by an early morning plasma aldosterone concentration (PAC) and renin level, and by overnight, attended polysomnography. RESULTS: OSA (apnea-hypopnea index [AHI] > or = 5/h) was present in 85% of subjects with resistant hypertension. In these subjects, PAC correlated with AHI (rho = 0.44, p = 0.0002) but not renin concentration. Median PAC was significantly lower in control subjects compared to subjects with resistant hypertension (5.5 ng/dL vs 11.0 ng/dL, p < 0.05) and not related to AHI. In male subjects compared to female subjects with resistant hypertension, OSA was more common (90% vs 77%) and more severe (median AHI, 20.8/h vs 10.8/h; p = 0.01), and median PAC was significantly higher (12.0 ng/dL vs 8.8 ng/dL, p = 0.006). CONCLUSION: OSA is extremely common in subjects with resistant hypertension. A significant correlation between PAC and OSA severity is observed in subjects with resistant hypertension but not in control subjects. While cause and effect cannot be inferred, the data suggest that aldosterone excess may contribute to OSA severity.     

A case-control study of obstructive sleep apnea-hypopnea syndrome in obese and nonobese chinese children

BACKGROUND: Obesity is a risk factor for obstructive sleep apnea-hypopnea syndrome (OSAHS) in adults. However, the prevalence of OSAHS in children is not clear, and the relationship between obesity and OSAHS remains controversial. METHODS: Obese children were recruited from the endocrinology, respiratory, and ear, nose, and throat clinics. Weight-matched, age-matched, and sex-matched children were recruited as control subjects. Standard questionnaires were administered, and a standardized physical examination was carried out. Lateral neck roentgenography, sleep polysomnography, full blood count, and arterial blood gas analysis were also performed. Children with body mass index z-scores of > 1.96 were considered to be obese. An adenoidal/nasopharygeal ratio of > 0.67 was considered to constitute adenotonsillar hypertrophy (ATH). OSAHS was defined as an apnea-hypopnea index (AHI) score of > 5 or obstructive apnea index (OAI) score of > 1. RESULTS: Ninety-nine obese children and 99 control subjects were recruited into the study. Obese patients had significantly higher AHI and OAI scores, and lower sleep efficiency and minimum arterial oxygen saturation (MinSao(2)) than control subjects. The prevalence of OSAHS was significantly higher in obese children with or without the ATH groups than their nonobese counterparts (odds ratio, 1.9 vs 108, respectively; 95% confidence interval, 1.21 to 4.7 vs 6.2 to 191, respectively). Obesity, tonsillar hypertrophy, and adenoid hypertrophy were independent risk factors for OSAHS (p < 0.001, p = 0.042, and p = 0.004, respectively). There was a positive correlation between the degree of obesity and AHI (r = 0.535; p < 0.001), and an inverse correlation between obesity and MinSao(2) (r = -0.507; p < 0.001). End-tidal CO(2), Paco(2), and bicarbonate levels were within the normal range. CONCLUSIONS: Obesity is a risk factor for OSAHS, and the degree of obesity is positively correlated with the severity of OSAHS.     

Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been associated with increased morbidity and mortality, principally from cardiovascular disease, but the impact of nasal continuous positive airway pressure (CPAP) therapy is unclear. METHODS: We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously, most of whom had been prospectively followed up, having been the subject of an earlier report on cardiovascular risk factors in OSAS patients. The average follow-up period was 7.5 years. We compared the cardiovascular outcomes of those patients who were intolerant of CPAP (untreated group, 61 patients) with those continuing CPAP therapy (107 patients). RESULTS: CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group (48.3 [interquartile range (IQR), 33.6 to 66.4] vs 36.7 [IQR, 27.4 to 55], respectively; p = 0.02), but age, body mass index, and time since diagnosis were similar. Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up (14.8% vs 1.9%, respectively; p = 0.009 [log rank test]), but no significant differences were found in the development of new cases of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie, death and new cardiovascular disease combined) were more common in the untreated group than in the CPAP-treated group (31% vs 18%, respectively; p < 0.05). CONCLUSIONS: The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS.     

Relationship between serum substance P levels and daytime sleepiness in obstructive sleep apnea syndrome

OBJECTIVE: We hypothesized that intermittent hypoxia might influence serum substance P levels, and that this effect might in turn contribute in excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: Fifty-five patients with newly diagnosed OSAS and 15 age-matched nonapneic control subjects were enrolled in this study. Full polysomnography was performed in all patients. Single blood samples were drawn between 8:00 am and 9:00 am after the sleep study. Substance P levels were analyzed with a competitive enzyme immunoassay (substance P EIA kit; Cayman Chemical; Ann Arbor, MI). RESULTS: There were no significant differences in age, gender, body mass index, smoking habit, and snoring between the two groups. Serum substance P levels in the OSAS group were significantly lower than that in the control group (p < 0.0001). Serum substance P levels were positively correlated with rapid eye movement sleep (r = 0.330, p = 0.049) and slow-wave sleep (r = 0.324, p = 0.049) phases. Serum substance P levels were negatively correlated with Epworth sleepiness scale score (r = - 0.253, p = 0.048), number of total apneas during the night (r = - 0.247, p = 0.036), number of respiratory events during the night (r = - 0.266, p = 0.024), apnea-hypopnea index (r = - 0.287, p = 0.015), respiratory arousal index (r = - 0.267, p = 0.026), time spent in apnea and hypopnea (r = - 0.307, p = 0.01), average oxygen desaturation (r = - 0.265, p = 0.026), and oxygen desaturation index (r = - 0.254, p = 0.031). CONCLUSION: We concluded that EDS seen in some of the OSAS patients might be associated with various pathophysiologic mechanisms including substance P levels.     

Leptin and leptin receptor gene polymorphisms in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea is common in obese people. Leptin is an adipocyte-derived signaling factor that has an important role in metabolic control. There is growing evidence that leptin regulation is altered in obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the relation between polymorphisms of the leptin and leptin receptor (LEPR) genes and OSAS. METHODS: The study population consisted of 130 patients with OSAS and 50 healthy control subjects. All the subjects were Japanese. Diagnostic polysomnography was performed in all patients and control subjects. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene and three single nucleotide polymorphisms (SNPs) [Lys109Arg (A/G) in exon 4, Gln223Arg (A/G) in exon 6, and Lys656Asn (G/C) in exon 14] in the LEPR gene were examined. RESULTS: There were no significant differences in allelic frequencies and genotype distributions of the examined polymorphisms of the leptin and LEPR genes between OSAS patients and control subjects. For the LEPR gene, the wild-type alleles of the Gln223Arg and Lys656Asn SNPs had a marginally significant effect on mild OSAS, which was defined as an apnea-hypopnea index from 10 and 20 events/h in the dominant model. CONCLUSIONS: The tetranucleotide repeat polymorphism of the leptin gene and the Lys109Arg, Gln223Arg, and Lys656Asn SNPs in the LEPR gene were not associated with OSAS in the Japanese population. Further studies are required to confirm the association of the wild types of Gln223Arg and Lys656Asn SNPs with the severity of OSAS.     

Predictors of decreased spontaneous baroreflex sensitivity in obstructive sleep apnea syndrome

BACKGROUND: The impact of obstructive sleep apnea syndrome (OSAS) on the arterial baroreflex, and its significance, is still under debate. We investigated the baroreflex sensitivity (BRS) during sleep in well-selected OSAS patient and control subject cohorts METHODS: We performed a prospective study of 10 non-OSAS subjects, 14 subjects with mild-to-moderate OSAS, and 14 male subjects with severe OSAS subjects. Groups were matched for age, body mass index, and other relevant variables. Subjects had no other disease and were not receiving regular medication. BP was monitored beat-by-beat (Portapres; Finapres Medical Systems; Amsterdam, the Netherlands) at night during polysomnography. Spontaneous BRS was assessed by the sequence technique. Heart-rate correction was also applied to calculate BRS at a heart rate (HR) of 60 beats/min (BRS-60) to account for intersubject variability in baseline HR. Eight suitable patients were treated with continuous positive airway pressure (CPAP), and BRS measurements were repeated 6 weeks later. RESULTS: BRS and BRS-60 were significantly lower in patients with severe OSAS than in patients with mild-to-moderate OSAS and in non-OSAS subjects, and a separate sleep-stage analysis revealed this difference to be evident in stage 2 non-rapid eye movement sleep and during nocturnal wakefulness. There was no difference in BRS and BRS-60 between non-OSAS subjects and patients with mild-to-moderate OSAS. In multivariate analysis, the desaturation index was the only independent predictor of depressed BRS. CPAP therapy significantly improved the BRS measures. CONCLUSION: Patients with severe OSAS demonstrate depressed BRS during sleep, which may contribute to the cardiovascular pathophysiology in OSAS patients.     

Impaired objective daytime vigilance in obesity-hypoventilation syndrome: impact of noninvasive ventilation

BACKGROUND: Obesity-hypoventilation syndrome (OHS) is efficiently treated by noninvasive ventilation (NIV). Sleep respiratory disturbances, reduced ventilatory drive, and excessive daytime sleepiness (EDS) are commonly reported, but their relationships remain unclear. OBJECTIVES: To characterize sleep breathing disorders encountered in patients with OHS, to compare low and normal CO(2) responders in terms of sleep abnormalities, subjective and objective measures of EDS, and to measure the changes induced by NIV on these parameters. METHODS: At baseline and after 5 nights of NIV, 15 consecutive patients (mean [+/- SD] age, 55 +/- 9 years; mean body mass index, 38.7 +/- 6.1 kg/m(2); Paco(2), 47.3 +/- 2.3 mm Hg) prospectively underwent polysomnography, CO(2) ventilatory response testing, Epworth sleepiness scale scoring, and the Oxford Sleep Resistance (OSLER) test, which is an objective vigilance test. RESULTS: OHS patients exhibited obstructive sleep apnea syndrome (mean apnea-hypopnea index, 62 +/- 32 events per hour) and rapid eye movement (REM) sleep hypoventilation (mean REM sleep time, 35 +/- 33%). Baseline CO(2) sensitivity was significantly related to the proportion of hypoventilation during REM sleep (r = 0.54; p = 0.037). Six patients showed abnormal sleep latencies during the OSLER test (71% of the low CO(2) responders vs 14% of the normal CO(2) responders). Low CO(2) responders exhibited significantly shorter sleep latencies during the OSLER test (23 +/- 14 vs 37 +/- 8 min, respectively; p = 0.05). Using NIV, diurnal blood gas levels were improved and REM sleep hypoventilation were suppressed. Objective sleepiness was improved in low CO(2) responders (p = 0.04). CONCLUSION: In OHS patients, the lower the daytime CO(2) response, the higher the proportion of REM sleep hypoventilation and daytime sleepiness. Short-term therapy with NIV improves all of these parameters.     

Relation between sleep duration,overweight, and metabolic syndrome in Korean adolescents

Background and aimsThe increasing prevalence of obesity has been paralleled by a trend of reduced sleep duration. Sleep is considered a modulator of neuroendocrine function. The aim of this study was to determine the relation between sleep duration, overweight, and metabolic syndrome in Korean adolescents.Methods and resultsThis study was based on data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV. Data from 1187 adolescents aged 12–18 years were included in the analysis. Subjects were classified according to self-reported sleep duration: ≤5 h, 6–7 h, 8–9 h, and ≥10 h. We analysed the association between sleep duration, overweight, and metabolic syndrome after adjustment for potential confounding variables. Body mass index (BMI), waist circumference (WC), and diastolic blood pressure (DBP) were higher in subjects who slept ≤5 h, and triglyceride level was higher in subjects who slept ≥10 h. According to logistic regression analysis, subjects who slept ≤5 h had a higher risk of overweight (odds ratio (OR) 2.04, 95% confidence interval (CI) 1.17–3.57) and elevated blood pressure (BP) (OR 2.11, 95% CI 1.22–3.65). We did not find any association between sleep duration and metabolic syndrome. Subjects who slept ≥10 h had a higher risk of hypertriglyceridemia (OR 2.17, 95% CI 1.14–4.13).ConclusionShort sleep duration was associated with overweight in adolescents. Although there was no association between sleep duration and metabolic syndrome, short sleep duration was associated with elevated BP and long sleep duration was associated with hypertriglyceridemia.     

Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure

BACKGROUND: Polysomnography findings between matched groups with obstructive sleep apnea (OSA) and OSA plus obesity-hypoventilation syndrome (OHS) before and after continuous positive airway pressure (CPAP), particularly in the extremely severe obese (body mass index [BMI] >or= 50 kg/m2), are unclear. DESIGN: Prospective study of subjects (BMI >or= 50 kg/m2) undergoing diagnostic polysomnography. Subjects with an apnea-hypopnea index (AHI) >or= 15/h underwent a second polysomnography with CPAP. The effect of 1 night of CPAP on sleep architecture, AHI, arousal indexes, and nocturnal oxygenation was assessed. OHS was defined as those subjects with obesity, PaCo2 > 45 mm Hg, and PaO2 < 70 mm Hg in the absence of lung disease. RESULTS: Twenty-three subjects with moderate-to-severe OSA and 23 subjects with moderate-to-severe OSA plus OHS underwent a 1-night trial of CPAP. Both groups were matched for spirometry, BMI, and AHI, but oxygen desaturation was worse in the OSA-plus-OHS group. CPAP significantly improved rapid eye movement (REM) duration (p < 0.005), AHI (p < 0.005), arousal indexes (p < 0.005), and percentage of total sleep time (TST) with oxygen saturation (SpO2) < 90% (p < 0.005) in both groups. In subjects with OSA plus OHS, 43% continued to spend > 20% of TST with SpO2 < 90%, compared to 9% of the OSA group, despite the adequate relief of upper airway obstruction. CONCLUSIONS: Extremely severe obese subjects (BMI >or= 50 kg/m2) with moderate-to-severe OSA plus OHS exhibit severe oxygen desaturation but similar severities of AHI, arousal indexes, and sleep architecture abnormalities when compared to matched subjects without OHS. CPAP significantly improves AHI, REM duration, arousal indexes, and nocturnal oxygen desaturation. Some subjects with OHS continued to have nocturnal desaturation despite the control of upper airway obstruction; other mechanisms may contribute. Further long-term studies assessing the comparative role of CPAP and bilevel ventilatory support in such subjects with OHS is warranted.     

Predictors of heartburn during sleep in a large prospective cohort study

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study. METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep. CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.     

Comparative impact of morbid obesity vs heart failure on cardiorespiratory fitness

BACKGROUND: We are in the midst of an obesity pandemic. Morbid obesity is associated with dyspnea on exertion and higher overall mortality rates. The relations between measures of cardiorespiratory fitness in morbidly obese persons compared to those with heart failure are unknown. METHODS: We compared cardiorespiratory fitness in patients with morbid obesity (n = 43) and established systolic dysfunction heart failure (n = 235), and in age-matched medical control subjects (n = 222) who had been referred for diagnostic exercise testing with simultaneous metabolic measurements. Only patients who completed an adequate test for maximum exertion manifested by a respiratory exchange ratio of > or = 1.10 were included in the study. RESULTS: The mean (+/- SD) body mass index (BMI) values for the three groups were 47.8 +/- 5.1, 30.1 +/- 5.7, and 33.8 +/- 9.0, respectively (p < 0.0001 for comparisons between morbidly obese patients and each comparator). The mean left ventricular ejection fraction for the heart failure group was 21.5 +/- 8.4%. Despite achieving higher peak heart rate and BP values, the morbidly obese patients had a mean maximum oxygen uptake (V(O2)max) that was similar to that of those with heart failure (17.8 +/- 3.6 vs 16.5 +/- 5.6 mL/kg/min, respectively; p = 0.14) and was considerably lower than that of the control group (17.8 +/- 3.6 vs 21.3 +/- 8.2 mL/kg/min, respectively; p = 0.007). In addition, among subjects in the control group, there was a graded inverse relation between BMI and V(O2)max. CONCLUSIONS: Morbidly obese individuals have severely reduced cardiorespiratory fitness that is similar to those with established systolic dysfunction heart failure. In addition, in those persons who are referred for stress testing for medical reasons, there is an inverse graded relationship between BMI and cardiorespiratory fitness. These data suggest that the impairment in V(O2)max in morbidly obese persons is related to BMI and possibly to other factors that impair peak cardiac performance. These findings are consistent with overall higher expected mortality in morbidly obese persons.     

Automatic titration and calculation by predictive equations for the determination of therapeutic continuous positive airway pressure for obstructive sleep apnea

BACKGROUND: It is unknown to what extent therapeutic continuous positive airway pressure (CPAP) levels obtained by various methods for the treatment of obstructive sleep apnea syndrome (OSAS) differ. This study aimed to explore the relationships among pressures titrated by an automatic CPAP (APAP) device and those calculated using different predictive equations, and to compare different ranges of calculated pressures with pressure values titrated by APAP. METHODS: In 140 OSAS patients, the 95th percentile pressure delivered by an APAP device (AutoSet T; ResMed; Sydney, NSW, Australia) during polysomnography, and pressures calculated by three equations (equation 1, Hoffstein and Miljetig [1994]; equation 2, Sériès et al [2000]; and equation 3, Stradling et al [2004]) were compared. RESULTS: Titrated and calculated pressures were weakly correlated. Significant differences were found between the mean (+/- SD) pressures (11.1 +/- 1.6, 8.3 +/- 1.8, 10.5 +/- 1.6, and 10.3 +/- 1.3 cm H(2)O, respectively) for 95th percentile APAP, and pressures calculated by equations 1, 2, and 3, except between values calculated by equations 2and 3. Differences between the calculated and APAP-derived pressures were negative for the low calculated values, and were progressively attenuated, or became positive, for the high values. The differences were smallest for calculated pressures from 11 to > 13 cm H(2)O, which were represented to a greater extent among the values calculated by equations 2 and 3 than by those calculated by equation 1. CONCLUSIONS: Considerably different therapeutic CPAP levels may be determined using various methods. The differences between the calculated and APAP-derived pressures are largest for calculated values of < 9 or > 15 cm H(2)O. The clinical consequences of these findings deserve further evaluation. Caution is still required before treating OSAS patients with calculated pressures.     

Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: a preliminary study

BACKGROUND: Sleep-disordered breathing is common in individuals with left ventricular (LV) dysfunction and has been treated with nocturnal positive airway pressure. We investigated whether treatment of central sleep apnea-hypopnea with bilevel positive airway pressure (BPAP) in ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) might improve LV function. METHODS: Fifty-two consecutive patients with IDCM who underwent both cardiac catheterization and standard polysomnography were enrolled in the study; individuals with obstructive sleep apnea syndrome were excluded. Subjects with an apnea-hypopnea index (AHI) >or= 20 episodes per hour were randomized to receive medical therapy either alone (n = 11) or together with BPAP (n = 10). RESULTS: LV end-diastolic pressure, pulmonary capillary wedge pressure, and plasma concentration of brain natriuretic peptide were significantly greater, and LV ejection fraction (LVEF) was significantly lower in patients with an AHI >or= 20/h (n = 21, 40.4%) than in those with an AHI < 20/h (n = 31, 59.6%). LVEF (30.5 +/- 1.6% vs 50.8 +/- 3.5%, p < 0.001) [mean +/- SE] and plasma concentration of brain natriuretic peptide (162.8 +/- 44.5 pg/mL vs 32.7 +/- 17.6 pg/mL, p = 0.02) were significantly increased and decreased, respectively, after treatment with BPAP (daily use, 4.8 +/- 0.3 h) for 3 months, whereas these parameters remained unchanged in the control subjects. CONCLUSIONS: Our findings suggest that treatment of coexisting central sleep apnea-hypopnea with BPAP improves LV function in ambulatory patients with IDCM. BPAP should thus be considered as a nonpharmacologic adjunct to conventional drug therapy in such patients.     

Visceral Adiposity and the Risk of Metabolic Syndrome Across Body Mass Index: The MESA Study

ObjectivesThis study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) categories.BackgroundThe regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals.MethodsWe studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS.ResultsHigher VF was associated with cardiometabolic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm²/m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval [CI]: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm²/m, 95% CI: 1.08 to 1.44 per 100 cm²/m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area.ConclusionsVF is modestly associated with BMI. However, across BMI, a single measure of and longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease.     

Treatment adherence and outcomes in flexible vs standard continuous positive airway pressure therapy

STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/- 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment. CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.     

Relationship between beta-blocker treatment and the severity of central sleep apnea in chronic heart failure

BACKGROUND: We sought to examine the relationship between use of beta-blockers and the severity of central sleep apnea (CSA) in patients with chronic heart failure. METHODS: We performed polysomnography in 45 patients with chronic heart failure (New York Heart Association functional class II/III and left ventricular ejection fraction < 50%) and examined the relationship between use of beta-blockers and the severity of CSA. Central apnea index (CAI) was used as an indicator of CSA. RESULTS: Patients receiving beta-blockers (ie, carvedilol; n = 27) had lower apnea-hypopnea index (AHI) and CAI than patients not receiving beta-blockers (n = 18) [mean +/- SD, 14 +/- 11 vs 33 +/- 17, p < 0.0001; and 1.9 +/- 3.2 vs 11 +/- 12, p = 0.0004, respectively]. AHI and CAI were negatively correlated with the dose of carvedilol (Spearman rho = - 0.61, p < 0.0001; and Spearman rho = - 0.57, p = 0.0002, respectively). Multiple regression analysis selected no use of beta-blockers as an independent factor of CAI (p = 0.0006). In five patients with CAI > 5 who underwent serial sleep studies, CAI decreased significantly after 6 months of treatment with carvedilol (9.5 +/- 4.9 to 1.3 +/- 2.4, p = 0.03). CONCLUSIONS: In patients with chronic heart failure, CAI was lower according to the dose of beta-blockers, and no use of beta-blockers was independently associated with CAI. In addition, 6 months of treatment with carvedilol decreased CAI. These results suggest that beta-blocker therapy may dose-dependently suppress CSA in patients with chronic heart failure.     

Cystic fibrosis patients have poor sleep quality despite normal sleep latency and efficiency

STUDY OBJECTIVES: Cystic fibrosis (CF) patients may be predisposed to poor sleep quality due to upper and lower airway abnormalities and impaired gas exchange. Previous sleep investigations of CF patients using single-night polysomnography have reported conflicting results. We hypothesized that sampling sleep for a prolonged period in a patient's normal environment may give a more representative assessment of sleep quality than a single-night polysomnogram, and that impaired sleep quality would correlate with pulmonary disease severity and self-assessed sleep quality. DESIGN: Using wrist actigraphy, we measured sleep quality in clinically stable CF patients and age-matched control subjects. In addition, each CF patient and control subject completed the following three questionnaires: the Epworth sleepiness scale; the Pittsburgh sleep quality index (PSQI); and the Medical Outcomes Study 36-item short form. RESULTS: Twenty CF patients and control subjects were enrolled in the study, and were well-matched for age, sex, and body mass index. The mean (+/- SD) FEV(1) for CF patients was 61.0 +/- 20.1% predicted. CF patients and control subjects had similar sleep duration, sleep latency, and sleep efficiency. However, CF patients had higher PSQI scores (6.45 vs 4.55, respectively; p = .04), a higher fragmentation index (FI) [31.72 vs 18.02, respectively; p < 0.001], and less immobile time (88.87 vs 91.89, respectively; p = 0.02). There was a significant correlation of FI with FEV(1) and PSQI scores. CONCLUSIONS: Stable CF patients have disrupted sleep, and sleep disruption may in part be related to the severity of pulmonary disease. In addition, the PSQI may be useful in detecting CF patients with poor sleep quality.     

Lung aeration during sleep

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.     

Association between polysomnographic measures of disrupted sleep and prothrombotic factors

BACKGROUND: Subjective sleep disturbances have been associated with increased risk of coronary artery disease (CAD). We hypothesized that disrupted sleep as verified by polysomnography is associated with increased levels of prothrombotic hemostasis factors previously shown to predict CAD risk. METHODS: Full-night polysomnography was performed in 135 unmedicated men and women (mean age +/- SD, 36.8 +/- 7.8 years) without a history of sleep disorders. Morning fasting plasma levels of von Willebrand Factor (VWF) antigen, soluble tissue factor (sTF) antigen, d-dimer, and plasminogen activator inhibitor (PAI)-1 antigen were determined. Statistical analyses were adjusted for age, gender, ethnicity, body mass index, BP, and smoking history. RESULTS: Higher total arousal index (ArI) was associated with higher levels of VWF (beta = 0.25, p = 0.011, DeltaR(2) = 0.045), and longer wake after sleep onset was associated with higher levels of sTF (beta = 0.23, p = 0.023, DeltaR(2) = 0.038). More nighttime spent at mean oxygen saturation < 90% (beta = 0.20, p = 0.020, DeltaR(2) = 0.029) and higher apnea-hypopnea index (AHI) [beta = 0.19, p = 0.034, DeltaR(2) = 0.024] were associated with higher PAI-1. There was a trend for a relationship between mean oxygen desaturation < 90% and PAI-1 (p = 0.053), even after controlling for AHI. Total ArI (beta = 0.28, p = 0.005, DeltaR(2) = 0.056) and WASO (beta = 0.25, p = 0.017, DeltaR(2) = 0.042) continued to predict VWF and sTF, respectively, even after controlling for AHI. CONCLUSIONS: Polysomnographically verified sleep disruptions were associated with prothrombotic changes. Measures of sleep fragmentation and sleep efficiency were related to VWF and sTF, respectively. Apnea-related measures were related to PAI-1. Our findings suggest that sleep disruptions, even in a relatively healthy population, are associated with potential markers of prothrombotic cardiovascular risk.     

Oxidative stress in obstructive sleep apnea

STUDY OBJECTIVES: To investigate the relationship between the severity of obstructive sleep apnea (OSA) and oxidative stress, which plays an important role in the pathogenesis of cardiovascular disease, and to elucidate the factors contributing to this relationship. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 128 consecutive subjects referred to the sleep laboratory of our hospital for screening or treatment of OSA. INTERVENTIONS: Not applicable. MEASUREMENTS: The severity of sleep-disordered breathing was evaluated by polysomnography. We measured urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an in vivo parameter of oxidative stress. Known risk factors for oxidative stress (age, obesity, smoking, hyperlipidemia, hypertension, and diabetes mellitus) were also investigated. RESULTS: Seventy subjects had nonsevere OSA (an apnea-hypopnea index [AHI] < 30), and 58 subjects had severe OSA (AHI >or= 30). Urinary 8-OHdG excretion was significantly higher in the severe OSA group (p = 0.03). Furthermore, urinary 8-OHdG excretion was significantly correlated with parameters of sleep-disordered breathing, including AHI, the apnea index, the oxygen desaturation index (ODI), the duration of oxygen saturation < 90%, and the respiratory arousal index. However, only ODI was significantly correlated with urinary 8-OHdG excretion after adjustment for confounding factors that are considered to be related to oxidative stress. CONCLUSIONS: The severity of OSA is independently associated with oxidative stress. Among various sleep-disordered breathing parameters, ODI is most closely related to oxidative stress.