Autonomic cardiovascular tests in children with obstructive sleep apnea syndrome

Study Objectives:

The aim of our study was to investigate cardiovascular autonomic activity during wakefulness, using cardiovascular tests, in a population of children with OSAS.

Design:

Prospective study.

Setting:

Sleep unit of an academic center.

Participants:

We included 25 children (mean age 10.2 ± 2.3 years) undergoing a diagnostic assessment for OSAS, and 25 age-matched healthy control subjects. All subjects underwent an overnight polysomnography and autonomic cardiovascular tests using parts of the Ewing test battery, which is a physiological test used for the assessment of autonomic function (head-up tilt test, Valsalva maneuver, deep breathing test).

Measurements and Results:

Eighteen of 25 children with OSAS (11 males, mean age 9.4 ± 1.7 years) concluded the study. OSAS patients had higher systolic blood pressure, diastolic blood pressure, baseline heart rate, the 30:15 index (which represents the RR interval at the 15th and 30th beats during the head up tilt test), and delta diastolic and systolic blood pressure during the head-up tilt test, while the heart rate variability during the deep breathing test was lower, compared with controls. A positive correlation between systolic and diastolic blood pressure and the apnea-hypopnea index (AHI), and negative between AHI and both the 30:15 index and Valsalva ratio, were found. Stepwise linear regression analysis detected a negative correlation between AHI and the 30:15 index and Valsalva ratio, a positive correlation between overnight mean oxygen saturation and delta heart rate, and between AHI and delta systolic blood pressure.

Conclusions:

Our data point to an increase in basal sympathetic activity during wakefulness and to an impaired reaction to several physiological stimuli, which is dependent on the severity of OSAS.

Citation:

Montesano M; Miano S; Paolino MC; Massolo AC; Ianniello F; Forlani M; Villa MP. Autonomic cardiovascular tests in children with obstructive sleep apnea syndrome. SLEEP 2010;33(10):1349-1355.     

Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea

STUDY OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a disorder that often presents with elevated serum aminotransferase levels. Although it has classically been linked with the metabolic syndrome, recent studies suggest NAFLD may also be associated with obstructive sleep apnea (OSA). This study evaluates the association between serum aminotransferase levels and factors connected with: either the metabolic syndrome (elevated body mass index [BMI], lipid profile, blood pressure, fasting glucose), or with OSA severity (apnea hypopnea index, lowest oxygen saturation level, oxygen desaturation index, percent of time below 90% saturation [%T<90]). DESIGN: Retrospective case series. PATIENTS AND SETTING: 109 adult patients with OSA at a university hospital general clinical research center. MEASUREMENTS AND RESULTS: Markers of hypoxia (lowest oxygen saturation level and %T<90), correlated significantly with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels (Pearson's r = -0.31 to -0.38, P <0.003), while apnea hypopnea index, body mass index, blood pressure, fasting glucose, triglyceride, and cholesterol levels did not. Hierarchical linear regression was then done to determine the best predictors of aminotransferase levels. Markers of metabolic syndrome were entered as one block and markers of sleep apnea as another. Regression analyses explained 16.3% of the variance in AST and 18.9% of the variance in ALT, with %T<90 playing the largest role. CONCLUSIONS: In patients with obstructive sleep apnea, serum aminotransferase levels are better predicted by markers of oxygen desaturation than by factors traditionally associated with the metabolic syndrome.     

骨折延迟愈合及骨不连与阻塞性睡眠呼吸暂停的相关性

背景：阻塞性睡眠呼吸暂停能影响成骨和/或破骨细胞及骨愈合相关调节蛋白,使骨折患者不易愈合或加重不愈合的程度。 目的：观察阻塞性睡眠呼吸暂停与骨不连的相关性。 方法：随机选取338例骨折的患者,其中骨愈合患者228例,骨不连110例,经便携式睡眠仪筛查出合并阻塞性睡眠呼吸暂停的骨不连患者11例,分析监测数据与临床资料的相关性。 结果与结论：与骨愈合患者相比,骨不连患者阻塞性睡眠呼吸暂停患病率较高(P < 0.05),比值比(OR)=2.422,95%CI=0.996~5.891,合并阻塞性睡眠呼吸暂停的骨不连患者愈合时间与最低血氧饱和度、平均血氧饱和度呈负相关(r分别为0.40和0.38,P < 0.05),骨痂X射线评分与最低血氧饱和度、平均血氧饱和度呈正相关(r分别为0.34和0.47,P < 0.05)。提示阻塞性睡眠呼吸暂停可能是骨不连新的危险因素之一。     

Hypertension, metabolic syndrome, prediabetes, and diabetes associated with obstructive sleep apnea syndrome

Objective

Associations between hypertension, metabolic syndrome, prediabetes, diabetes, and obstructive sleep apnea syndrome (OSAS) were assessed in a prospective single center clinical study including patients from an outpatient sleep clinic and an inpatient sleep lab.

Methods

The G?rlitz Metabolic Study is a prospective trial assessing the relationship between current definitions of the metabolic syndrome (Adult Treatment Pannel?III, ATP?3; International Diabetes Federation, IDF; metabolic vascular syndrome, MVS), its constituting parameters, and OSAS in different patient cohorts in Upper Lusatia, Germany. In addition, the diagnostic relevance of a newly developed scoring system, the Carolus Sleep Score (CSS), was compared to the Epworth Sleepiness Scale (ESS). A total of 2,362?patients were consecutively included in the study. The statistics were done exploratively.

Results

Outpatients with OSAS who had not yet been treated had a mean blood pressure of 157/94?mmHg with a hypertension prevalence of 71%, while the mean blood pressure of those already treated was 153/89?mmHg with a hypertension prevalence of 68%. In 42% of the obstructive sleep apnea (OSA) and in 27% of the non-OSA patients, the criteria of all three definitions of the metabolic syndrome were fulfilled. The coefficients of correlation were 0.22 for the respiratory disturbance index (RDI) vs. body mass index (BMI), 0.26 for RDI vs. abdominal circumference, 0.19 for CPAP vs. BMI, and 0.25 for CPAP vs. abdominal circumference. There was a diabetes prevalence of 27% in the OSA patients and 16% in the non-OSA patients. In addition, when evaluating a subgroup of OSA patients with the same mean abdominal circumference as the non-OSA patients, the prevalences of hypertension, metabolic syndrome, and diabetes were still higher in those who suffered from OSA. The CSS clearly proved to be more suitable for primary OSA screening than the ESS. In addition, the CSS correlated considerably better with the RDI (r=0.36) than the ESS (r=0.21).

Conclusion

Despite the uncontrolled real-life clinical setting, the previously reported relevance of OSA for cardiovascular and metabolic disturbances was clearly verified. The data unequivocally show that the recommendations in the different hypertension and diabetes guidelines to look for hypertension and diabetes, respectively, in OSA patients and vice versa for OSAS in hypertensive and diabetic patients should be regarded seriously. The CSS seems to be superior for screening patients compared to the ESS.     

Effect of nocturnal hypoxia on pulmonary hemodynamics in patients with obstructive sleep apnea

Effects of apnoea induced nocturnal hypoxia on pulmonary haemodynamics (PH) in pts with OSA are still under debate. We studied PH in 67 pts (64 M and 3 F) mean +/- SD: age 45 +/- 8 years, with severe OSA, AHI 62 +/- 22. Patients had normal spirometry: FVC 98 +/- 15% N, FEV1 97 +/- 16% N and arterial blood gases--PaO2 72 +/- 10 mmHg, PaCO2 40 +/- 4 mmHg. PH were studied using Swan-Ganz thermodilution catheter. PH were within normal range: right atrial pressure 4.2 +/- 2.7 mmHg, right ventricular systolic/enddiastolic pressure 28.1 +/- 7.1/5.0 +/- 3.3 mmHg, mean pulmonary artery pressure (PAP) 15.8 +/- 4.6 mmHg, mean pulmonary wedge pressure (PW) 6.8 +/- 3.1 mmHg, cardiac output (CO) 5.6 +/- 2.2 L/min. and pulmonary vascular resistance (PVR) 150 +/- 83 dyn.sec.cm-5. During exercise (44 pts) PAP rose from 15.8 +/- 4.3 to 29.8 +/- 9.4 mmHg, PW rose from 6.8 +/- 3.2 to 12.6 +/- 6.8 mmHg and CO from 4.9 +/- 1.9 to 9.2 +/- 4.2 L/min. All patients presented with nocturnal desaturations. Mean oxygen saturation (SaO2 mean) was: 87.4 +/- 5.4%, minimal saturation (SaO2 min) was 57.4 +/- 15.9%. Time spent in desaturation SaO2 < 90% (T90) was 50.7 +/- 26.5%. Results of PH investigations were related to results of pulse oximetry. Linear regression analysis showed week negative correlations between SaO2 mean and: PAP (r = -0.37 p = 0.003), PVR (r = -0.37 p = 0.007), and positive correlation between T90 and PAP (r = 0.37 p = 0.008). We conclude that there is no diurnal pulmonary hypertension at rest in patients with severe OSA and normal lung function even in the presence of severe overnight nocturnal desaturations. In half of studied patients we observed pulmonary hypertension during exercise.     

Snoring sounds variability as a signature of obstructive sleep apnea

Snoring sounds vary significantly within and between snorers. In this study, the variation of snoring sounds and its association with obstructive sleep apnea (OSA) are quantified. Snoring sounds of 42 snorers with different degrees of obstructive sleep apnea and 15 non-OSA snorers were analyzed. The sounds were recorded by a microphone placed over the suprasternal notch of trachea, simultaneously with polysomnography (PSG) data over the entire night. We hypothesize that snoring sounds vary significantly within a subject depending on the level of obstruction, and thus the level of airflow. We also hypothesize that this variability is associated with the severity of OSA. For each individual, we extracted snoring sound segments from the respiratory recordings, and divided them into three classes: non-apneic, hypopneic, and post-apneic using their PSG information. Several features were extracted from the snoring sound segments, and compared using a nonparametric statistical test. The results show significant shift in the median of features among the snoring sound classes (p < 0.00001) of an individual. In contrast to hypopneic and post-apneic classes, the characteristics of snoring sounds did not vary significantly over time in non-apneic class. Therefore, we used the total variation norm of each subject to classify the participants as OSA and non-OSA snorers. The results showed 92.9% sensitivity, 100% specificity and 96.4% accuracy.     

The relationship of daytime hypoxemia and nocturnal hypoxia in obstructive sleep apnea syndrome

QUESTION OF THE STUDY: Prevalence and determinants of daytime hypoxemia in patients with obstructive sleep apnea (OSA) syndrome are not well established. The aims of this study, conducted in a large series of OSA patients, were to estimate the prevalence of daytime hypoxemia, to assess the reciprocal effects between daytime PaO2 and nocturnal SpO2, and to investigate the direct and indirect role of sleep apnea severity in determining feedback gas exchange abnormalities. MATERIALS AND METHODS: In 456 patients a daytime hypoxemia-nocturnal hypoxia feedback structural equations model was designed. PaO2 adjusted for age (% of predicted), percent sleep time spent with SpO2 <90% (TST90), oxygen desaturation index and the apnea-hypopnea index, were determined as the measures of daytime hypoxemia, nocturnal hypoxia, and sleep apnea severity, respectively, after adjusting for the severity of obesity and lung volumes. RESULTS: The TST90-PaO2 feed-back structural equations modeling showed that daytime PaO2 was inversely related (P<0.001) to nocturnal hypoxia (-4.0% of PaO2 per 1 SD of TST90). The severity of OSA (-1.0%) was an indirect determinant of daytime PaO2 via the TST90 pathway. In contrast, daytime PaO2 did not influence (P>0.05) the extent of nocturnal hypoxia. CONCLUSIONS: In OSA patients, the extent of nocturnal hypoxia seems to be both a direct determinant and a mediator of the indirect effect of sleep apnea on the development of daytime hypoxemia.     

Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), endsystolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis.     

Microsleep as a marker of sleepiness in obstructive sleep apnea patients

We hypothesized that: (a) the presence of microsleep (MS) during a Maintenance Wakefulness Test (MWT) trial may represent a reliable marker of sleepiness in obstructive sleep apnea (OSA) patients; (b) the number of MSs will be higher in sleepy versus non‐sleepy patients with a borderline MWT mean sleep latency; and (c) scoring MS during MWT analysis may help physicians to recognize patients with a higher degree of sleepiness. We analysed the MWT data of 112 treatment‐naïve OSA patients: 20 with short sleep latency (SL, sleep latency <12.8 min), 43 with borderline latency (BL, sleep latency between 12.8 and 32.6 min) and 49 with normal latency (NL, sleep latency >32.6 min). Microsleep was identified in all SL, in 42 BL and in 18 NL patients, with a median latency of 5.6 min. Accordingly, patients were classified into two subgroups: group A (n = 43) with microsleep latency <5.6 min and group B (n = 69) with microsleep latency >5.6 min when present. The mean sleep latency in the MWT was 14.5 ± 7.5 min in group A and 34.6 ± 7.4 min in group B (p < 0.0001). The number of microsleep episodes during each MWT trial was higher in group A than in group B. Sleep latency survival curves demonstrated different patterns of sleep latency in these groups (log‐rank test <0.0001). This finding was confirmed in a Cox proportional hazard analysis: the presence of a mean MS latency <5.6 min is associated with an increasing risk of falling asleep during the MWT (RR, 1.93; 95 CI 1.04–3.6; p = 0.03). We conclude that the detection of microsleep may help in discriminating OSA patients with and without daytime vigilance impairment.     

Effect of CPAP therapy on daytime cardiovascular regulations in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence that causes pathological changes in cardiovascular regulation during the night and also during daytime. We investigated whether the treatment of OSA at night by means of continuous positive airway pressure (CPAP) improves the daytime consequences. Twenty-eight patients with OSA, 18 with arterial hypertension, 10 with normal blood pressure, were investigated at baseline and with three months of CPAP treatment. Ten age and sex matched healthy control subjects were investigated for comparisons. We recorded a resting period with 20min quiet breathing and an exercise stress test during daytime with ECG and blood pressure (Portapres). The bicycle ergometry showed a significant reduction of the diastolic blood pressure at a work load of 50W and 100W (p<0.05 and p<0.01, respectively) and a decrease of the heart rate recovery time after the stress test (p<0.05). These results indicate a reduction of vascular resistance and sympathetic activity during daytime. The coupling analysis of the resting periods by means of symbolic coupling traces approach indicated an effect of the CPAP therapy on the baroreflex reaction in hypertensive patients where influences of the systolic blood pressure on the heart rate changed from pathological patterns to adaptive mechanisms of the normotensive patients (p<0.05).     

Haptoglobin polymorphism is a risk factor for cardiovascular disease in patients with obstructive sleep apnea syndrome

STUDY OBJECTIVES: Obstructive sleep apnea syndrome is associated with a marked increase in the risk for cardiovascular disease. Increased oxidative stress and leukocyte adhesiveness have been implicated as fundamental pathophysiologic mechanisms underlying the increased susceptibility in these patients. Haptoglobin is an antioxidant and immunomodulatory protein encoded by 2 alleles with profoundly different biophysical and biochemical properties. We therefore sought to determine if the haptoglobin phenotype was a determinant of cardiovascular disease in patients with obstructive sleep apnea syndrome. DESIGN: Haptoglobin phenotype was determined by gel electrophoresis in 465 patients with and 757 individuals without obstructive sleep apnea syndrome. SETTING: Eight-bed Technion Sleep Medicine Center in Haifa, serving the northern part of Israel. PARTICIPANTS: Patients referred for sleep recordings because of suspected breathing disorders in sleep and healthy industry workers. MEASUREMENTS AND RESULTS: Patients with obstructive sleep apnea syndrome and cardiovascular disease had a significantly different distribution of the 3 haptoglobin phenotypes as compared to patients with obstructive sleep apnea syndrome but without cardiovascular disease. No difference in the haptoglobin phenotype frequency was found between controls with and without cardiovascular disease. Log linear analysis revealed a significant interaction effect of haptoglobin phenotype and the presence of sleep apnea on the presence of cardiovascular disease. Logistic regression analysis revealed that the risk of cardiovascular disease in sleep apnea patients younger than 55 years with haptoglobin 2-2 was 2.32-fold higher than in their counterparts with haptoglobin 2-1. CONCLUSIONS: These results suggest that haptoglobin phenotype is an important risk factor in determining susceptibility to cardiovascular disease in obstructive sleep apnea syndrome, which may be mediated by the decreased antioxidant and antiinflammatory actions of the haptoglobin 2 allelic protein product.     

Dynamic assessment of oropharynx with ultrasonography as a screening tool for obstructive sleep apnea

Ultrasonography is an easily available and portable tool to assess the dynamic changes in the upper airway and surrounding soft tissue. This study aimed to evaluate the utility of oropharynx ultrasonography as a screening tool for obstructive sleep apnea (OSA). The study sequentially enrolled overweight individuals (body mass index >25 kg/m²) and subjected them to OSA screening tools (Berlin questionnaire, Epworth Sleepiness Scale and STOP-Bang scores), ultrasonography of the oropharynx followed by overnight polysomnography. A total of 30 healthy individuals were also recruited as controls. Detailed dynamic and static ultrasonography measurements of the oropharynx and surrounding tissue were done. The diagnostic ability of various ultrasonography parameters to detect OSA was determined using receiver operating characteristic curve analysis. A total of 63 subjects were enrolled, with 33 in the OSA group and 30 in non-OSA overweight group. All baseline characteristics were similar in the two groups. Except for the dynamic measurements of oropharynx (Retropalatal% change-inspiration, retropalatal% change-Muller manoeuvre, retroglossal% change-inspiration, and retroglossal% change-Muller manoeuvre) all other parameters were similar in the OSA and non-OSA overweight subjects. The area under the receiver operating characteristic curve was highest for retropalatal% change-inspiration: 0.989, followed by retropalatal% change-Muller manoeuvre: 0.988. Both were also significant predictors of OSA with odds ratios of 0.338 (p = 0.003; 95% confidence interval [CI] 0.164–0.696) and 0.346 (p = 0.018; 95% CI 0.143–0.837), respectively. Ultrasonography provides a near complete picture of the dynamic changes and collapsibility of the oropharynx and can be an effective tool in screening for OSA.     

阻塞性睡眠呼吸暂停综合征病人术前心血管系统评估

目的对阻塞性睡眠呼吸暂停综合征(OSAS)病人术前心血管系统及其相关因素进行评估。方法通过调查行择期UPPP的57例病人,对心血管系统参数及其相关因素进行对比、统计和分析。结果OSAS病人合并高血压、冠心病的发生率显著增高。分别达75.44%和14.04%。心电图异常率达40.35%。OSAS病情越重,合并症越多且重。结论OSAS可继发高血压、冠心病等症,对机体造成严重损害。术前应认真对其心血管功能进行评估,以减少围术期危险心血管事件发生。     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.