Cardiovascular morbidity in patients with obstructive sleep apnea in relation to the severity of respiratory disorder

BASIC PROBLEM AND OBJECTIVE: Untreated patients with obstructive sleep apnoea (OSA) have an increased risk of death from cardiovascular (cv) disease. This study was undertaken to determine the disease spectrum in patients with sonographically proven OSA (apnoea-hypopnoea index > or = 5), with special reference to cv risk factors and accompanying diseases in relation to the severity of their respiratory abnormalities. The study's aim was to clarify what risk factors and accompanying diseases were associated with different degrees of OSA. PATIENTS AND METHODS: A systematic recording of cv risk factors and accompanying diseases as well as their association to the severity of nocturnal respiratory disorders was made for 175 patients (165 men, 10 women, mean age 54 +/- 10.2 years) with sonographically proven OSA (mean apnoea-hypopnoea index 37 +/- 24.4). RESULTS: The body mass index (BMI) was significantly related to the severity of the respiratory disorder (apnoea-hypopnoea index, AHI, P < 0.05, odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.15-3.31). In a multivariate analysis, nocturnal breathing pause (P < 0.05; OR: 3.8; 95% CI: 1.3-11.1), left ventricular hypertrophy (P < 0.01; OR: 3.9; 95% CI: 1.5-10.3) and diabetes mellitus (P < 0.05; OR: 4.2, 95% CI: 1.2-14.7) were independently associated with a high-grade breathing disorder (AHI > or = 20). The incidence of left ventricular hypertrophy rose with an increasing severity of nocturnal OSA. CONCLUSION: These data indicate that in patients with high-grade OSA (AHI > or = 20) there is a further grouping together of cardiovascular risk factors, namely increasing body weight, diabetes mellitus, arterial hypertension and left ventricular hypertrophy; they explain the increased mortality rate among these patients from vascular complications.     

Pulmonary hypertension in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular morbidity, including pulmonary hypertension. Little is known about factors influencing the degree of pulmonary hypertension and left ventricular dysfunction in patients with OSAS, especially in the absence of concomitant lung disease. METHODS: Right heart catheterization, arterial blood gas analysis, and pulmonary function tests were performed in 92 consecutive patients (81 men and 11 women; mean +/- SD age, 53.1 +/- 11.0 years) with polysomnographically verified OSAS, in whom clinically significant lung disease was excluded. RESULTS: Eighteen patients (20%) had mild pulmonary hypertension; 8 (44%) of them also had increased pulmonary capillary wedge pressures (Ppew). Left ventricular dysfunction was associated with arterial hypertension. Only Ppcw (r = 0.51; P < .001) and the percentage of time during sleep spent with an oxygen saturation below 90% (as an indicator of the severity of OSAS) (r = 0.34; P = .003) were significantly and independently associated with pulmonary artery pressure. CONCLUSIONS: Obstructive sleep apnea syndrome can cause mild pulmonary hypertension, even in the absence of pulmonary disease. In these patients, pulmonary hypertension is of the postcapillary type, or-in patients with normal left ventricular function-strongly related to the severity of OSAS. Our findings indicate that OSAS may constitute an important, and independent, risk factor for pulmonary hypertension.     

Chemical control of breathing in patients with obstructive sleep apnea

The authors have studied chemical control of breathing in 37 normocapnic patients with OSA. These patients had increased apnea-hypopnea index (AHI = 51 +/- 22), obesity (BMI = 32.4 +/- 5.6 kg/m2) and normal lung function tests. Control group consisted of 20 healthy subjects with normal weight (BMI = 23.1 +/- 2.4 kg/m2). Respiratory responses (ventilatory and P0.1) to hypercapnic and hypoxic stimulation during rebreathing tests were measured with computerized methods. The obtained results in OSA patients were compared with the data of the control group. The results exceeding mean values of the control group above 1.64 SD were recognized as hyperreactive responses. The majority e.g. 26 patients (OSA-N) had normal respiratory responses during hypercapnic stimulation. delta V/delta PCO2 = 16.8 +/- 4.5 L/min/kPa, P0.1/delta PCO2 = 3.5 +/- 2.4 cm H2O/kPa/. In remaining 11 patients (OSA-H) respiratory responses were significantly increased delta V/delta PCO2 = 39.1 +/- 18.8 L/min/kPa, P0.1/delta PCO2 = 8.6 +/- 3.9 cm H20/kPa). During isocapnic hypoxic stimulation majority e.g. 25 patients (OSA-H) had significantly increased respiratory responses delta V/delta SaO2 = 3.28 +/- 1.63 L/min/%, delta P0.1/delta SaO2 = 0.54 +/- 0.43 cm H2O/%/. In remaining 12 patients (OSA-N) respiratory responses were within normal limits delta V/SaO2 = 1.2 +/- 0.28 L/min/%, delta P0.1/ delta SaO2 = 0.21 +/- 0.07 cm H2O/%/. The above results indicated, that majority OSA patients (67.5%) had increased ventilatory and P0.1 responses to hypoxic stimulation. Among them also 11 patients had increased respiratory responses to hypercapnia. It seems, that increased respiratory responses to hypoxic stimulus in OSA patients are symptoms of protective reaction to hypoxaemia occurring during repetitive sleep apnoea and reveals increased neuro-muscular output.     

Cardiovascular manifestations of obstructive sleep apnea. Effects of the treatment

There is a direct relationship between obstructive sleep apnea and high blood pressure, ischemic heart disease and cerebrovascular disorders. Obstructive sleep apnea, defined as an intermittent complete or partial upper airway obstruction during sleep, occurs in approximately 4% of adults, although some authors suggest a 9% prevalence in women and 24% in men. Due to its high frequency, this condition must be considered as another cardiovascular risk factor that should be prevented and adequately treated.     

Assessment of ventilatory neuromuscular drive in patients with obstructive sleep apnea

The presence of abnormalities of the respiratory center in obstructive sleep apnea (OSA) patients and their correlation with polysomnographic data are still a matter of controversy. Moderately obese, sleep-deprived OSA patients presenting daytime hypersomnolence, with normocapnia and no clinical or spirometric evidence of pulmonary disease, were selected. We assessed the ventilatory control and correlated it with polysomnographic data. Ventilatory neuromuscular drive was evaluated in these patients by measuring the ventilatory response (VE), the inspiratory occlusion pressure (P.1) and the ventilatory pattern (VT/TI, TI/TTOT) at rest and during submaximal exercise, breathing room air. These analyses were also performed after inhalation of a hypercapnic mixture of CO2 (delta P.1/delta PETCO2, delta VE/delta PETCO2). Average rest and exercise ventilatory response (VE: 12.2 and 32.6 l/min, respectively), inspiratory occlusion pressure (P.1: 1.5 and 4.7 cmH2O, respectively), and ventilatory pattern (VT/TI: 0.42 and 1.09 l/s; TI/TTOT: 0.47 and 0.46 l/s, respectively) were within the normal range. In response to hypercapnia, the values of ventilatory response (delta VE/delta PETCO2: 1.51 l min-1 mmHg-1) and inspiratory occlusion pressure (delta P.1/delta PETCO2: 0.22 cmH2O) were normal or slightly reduced in the normocapnic OSA patients. No association or correlation between ventilatory neuromuscular drive and ventilatory pattern, hypersomnolence score and polysomnographic data was found; however a significant positive correlation was observed between P.1 and weight. Our results indicate the existence of a group of normocapnic OSA patients who have a normal awake neuromuscular ventilatory drive at rest or during exercise that is partially influenced by obesity.     

Fluoroscopic MR of the pharynx in patients with obstructive sleep apnea

PURPOSE: The purpose of our study was to introduce an ultrafast MR imaging technique of the pharynx as a diagnostic tool for viewing the mechanism of obstruction in patients with obstructive sleep apnea. METHODS: Six healthy volunteers and 16 patients with obstructive sleep apnea were examined on a 1.5-T whole-body imager using a circular polarized head coil. Ultrafast two-dimensional fast low-angle shot sequences were obtained in midsagittal and axial projections during transnasal shallow respiration at rest, during simulation of snoring, and during performance of the Müller maneuver. All patients underwent physical examination, transnasal fiberoptic endoscopy, and polysomnography. RESULTS: Five to six images were obtained per second with an in-plane resolution of 2.67 x 1.8 mm and 2.68 x 2.34 mm, allowing visualization of motion of the tongue, soft palate, uvula, and posterior pharyngeal surface. MR findings correlated well with results of clinical examination. The length of obstruction in the oropharynx, which cannot be ascertained by transnasal endoscopy of the pharynx, was clearly visible MR images. Differences between patients with obstructive sleep apnea and healthy subjects in terms of the degree of obstruction in the velopharynx and oropharynx depicted on MR images during the Müller maneuver were highly significant. CONCLUSION: We believe that ultrafast MR imaging is a reliable noninvasive method for use in the evaluation of obstructive sleep apnea.     

Anamnestic and polygraphic parameters in obstructive sleep apnea syndrome patients with reduced nasal respiration during the day in comparison with obstructive sleep apnea patients with normal nasal respiration

Nasal obstruction is a predictive factor for snoring and may contribute to the development of an obstructive sleep apnea syndrome (OSAS). The aim of this study was to further evaluate the impact of nasal obstruction in OSAS. Therefore, we investigated 2 groups of OSAS-patients, matched pairs concerning gender, age, and BMI: OSAS-patients with nasal obstruction (N, n = 28), total nasal airflow < 500 ccm/s (referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s), and 28 OSAS-patients without nasal obstruction (control-group K, total nasal airflow > 700 ccm/s [referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s]). We performed anterior rhinomanometry, lung-function testing, cardio-respiratory polygraphy, and patients answered a standardized questionnaire. We found the following significant differences: 1) N complained more often (n = 17) about dyspnea at night than K (n = 7, p < 0.05, Chi2-test). 2) N had a higher apnea index (20.4 +/- 19.0/h) than K (9.6 +/- 10.0/h, p < 0.05, Student's t-test). There were, however, no significant differences concerning lung function, number of nocturnal hypopneas, nocturnal SaO2 and heart rate. Our results underline the importance of nasal ventilation in the pathogenesis of OSAS. At least in moderate cases of OSAS a therapy of nasal obstruction might be of success in order to abolish nCPAP-therapy or might reduce nasal problems during nCPAP-therapy and thus ameliorate patient's therapy compliance.     

Cephalometric assessment in obstructive sleep apnea

It is reported that some specific craniofacial characteristics are associated with obstructive sleep apnea syndrome (OSAS). To test this finding, the present study developed and assessed the feasibility of a craniofacial index score (CIS) in differentiating patients with OSAS from habitual snorers. Anthropometric measurements and lateral head radiographs were obtained on 24 male and 4 female patients with OSAS who had physician-diagnosed OSAS (respiratory disturbance index (RDI) >20), and 25 male and 5 female habitual snorers (RDI <20). Thirteen cephalometric and four anthropometric measure- ments were used in a discriminant model to construct the CIS. The model was able to correctly classify 82.1% of the OSAS group and 86.7% of the snoring group. In addition, variables that were related to the soft tissues, hyoid bone to mandibular plane, Body Mass Index, and soft palate length had the highest predictive value. These findings indicate that a CIS constructed from cephalometric and anthropometric measurements can be used to identify subjects with and without OSAS.     

Incidence of parasomnias in children with obstructive sleep apnea

The incidence of parent-reported parasomnias in children with obstructive sleep apnea (OSA) is increased in comparison with a normative age-matched sample of children but is not higher than that for a similar clinical sample of children with a diagnosed behavioral sleep disorder.     

The relationship between the severity of sleep apnea syndrome and 24-h blood pressure values in patients with obstructive sleep apnea

Analysis of the nucleotide sequence in the 5' flanking region of bacteriophage T4 gene 25 revealed three potential Shine and Dalgarno sequences, SD1, SD2 and SD3, with a spacing of 8, 17 and 27 nucleotides from the initiation codon of this gene, respectively. Results of our experiments in the bacteriophage T7 expression system clearly demonstrate that the SD3 sequence is required for efficient expression of gene 25. We propose the existence of a stem-loop structure that includes SD1 and SD2 sequences and brings the SD3 sequence to a favourable spacing with the initiation codon of gene 25. Since the predicted secondary structure in the translational initiation region of gene 25 is relatively unstable and the SD3 sequence, GAGG, is more typical than the SD1 sequence, GAG, we suggest that this structure could control the level of gene expression.     

Pharyngeal critical pressure in patients with obstructive sleep apnea syndrome. Clinical implications

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.     

Sex-specific sleep anamnesis in obstructive sleep apnea syndrome?

Although the prevalence of obstructive sleep apnea syndrome (OSAS) is about 4% in men and 2% in women, women are underrepresented in clinical routine. The aim of this study was to determine whether differences in clinical features of OSAS may in part explain the bias observed. 224 men and 24 women with polysomnographically confirmed OSAS filled in a symptom-focussed multiple-choice questionnaire. Polysomnographical results were comparable in both groups. With regard to snoring, daytime sleepiness and tendency of falling asleep there were no differences between both groups. Women more frequently complained about difficulties of initiating and maintaining sleep and about apneas. Further investigations have to concentrate on the pathomechanisms of OSAS in women which may in part explain the gender differences in sleep apnea associated symptoms.     

Screening for obstructive sleep apnea in patients presenting for snoring surgery

Excessive mortality is associated with obstructive sleep apnea (OSA). Therefore it is important to diagnose OSA in patients presenting for snoring surgery. A prospective study was performed to develop screening models to detect OSA compared with universal polysomnography for sensitivity and cost. Multivariate analysis of 150 consecutive patients was based on clinical data, questionnaire data, and polysomnography. Two screening models obtained 100% sensitivity and reduced the need for polysomnograms. Cost savings of screening based on clinical data was projected to be $35 to $80 per patient using reported prevalence rates of OSA among snorers. A screening model for OSA using clinical data alone is more cost-effective than one that combines these data with pulse oximetry data, but savings over universal polysomnography were modest.     

Neuropsychological functioning and determinants of morning alertness in patients with obstructive sleep apnea syndrome

Neuropsychological functioning is reported to be impaired in patients suffering from obstructive sleep apnea syndrome (OSAS). This syndrome is characterized by nocturnal respiratory disturbances, blood oxygen desaturations, sleep fragmentation, and excessive daytime sleepiness. Opinions are divided concerning the exact relationship between the observed cognitive deficits, nocturnal hypoxia, sleep disruption, and impaired daytime alertness. In the present study, morning neuropsychological function of 26 moderate to severe middle-aged sleep apneics is compared to that of 22 primary insomniacs. There were no performance differences on a range of neuropsychological tests among the two patient groups. In addition, the data suggest that morning alertness impairment, which is closely associated with a lack of slow wave sleep (SWS) and rapid eye movement (REM) sleep, is of major importance in inducing poorer cognitive performance in patients with moderate to severe sleep apnea.     

Enuresis and obstructive sleep apnea in adults

Adult enuresis is an unusual symptom of obstructive sleep apnea (OSA). Although it is described as a classic symptom of childhood OSA, enuresis is encountered infrequently in adult sleep medicine. Five adults with enuresis associated with sleep apnea presented to our Sleep Disorders Center. In all five cases, the onset of enuresis was associated with the progression of sleep apnea symptoms. In each case, the enuresis resolved with treatment with nasal continuous positive airway pressure. Current medical literature on the postulated mechanisms of nocturia and enuresis in sleep apnea is reviewed. Based on the experience of the authors and review of the medical literature, one may conclude that severe OSA may lead to new-onset enuresis in adults and that effective treatment of OSA is associated with resolution of enuresis.     

Treatment of otherwise normal children with obstructive sleep apnea

There are many therapeutic approaches to children with OSA. Treatment should be considered only when the severity of the syndrome has been established by objective testing including overnight polysomnography. Anatomic abnormalities, including adenotonsillar hypertrophy, must be defined. Once the severity and underlying cause of OSA have been established, the most appropriate approach can be devised for the individual. Mild cases may simply be observed. Moderate or severe patients whose nasopharynx is obstructed by lymphoid hyperplasia may be treated with adenotonsillectomy. If surgery is declined or contraindicated, nasal CPAP is effective. CPAP is also useful as a temporary measure while weight loss is being effected.     

Surgical options for obstructive sleep apnea

The pathology associated with obstructive sleep apnea is cumulative and progressive. When patients fail to improve with continuous nasal airway pressure or other, less-invasive treatments, surgery should be considered. The initial approach to the surgical patient is identification of all areas of potential obstruction. There are often several sites of obstruction, which can occur anywhere in the upper respiratory tract. One or more procedures may be needed to address these areas. The objective of surgery is to relieve these obstructing sites without interfering with the normal functionality of the upper airway.