[Obstructive sleep apnea syndrome and upper airway resistance syndrome. Gender-related differences]. / Obstruktives Schlafapnoesyndrom und Upper Airway Resistance Syndrom: Geschlechtsspezifische Unterschiede.

BACKGROUND: The aim of this study was to assess potential gender-related differences in the clinical presentation and polysomnographic parameters of patients with obstructive sleep apnea syndrome (OSAS) and upper airway resistance syndrome (UARS). PATIENTS AND METHODS: The polysomnographic variables and medical histories of 165 women with OSAS and 66 women with UARS from two sleep disorder clinics, presenting consecutively between 2000 and 2006 were retrospectively analyzed. These women were matched with an identical number of men, presenting during the same time frame, by diagnostic category (UARS/OSAS), age, and BMI. RESULTS: The relative percentage of women diagnosed with UARS varied dependent on their menopausal status. Postmenopausal women presented significantly less frequently with UARS than pre- and perimenopausal women. The adjusted odds ratio for a diagnosis of OSAS vs UARS was 5.5 (CI: 2.3;13.2; P=0.001) compared to premenopausal women. UARS women had a 30 min higher subjective sleep need than UARS men (8.2+/-1.1 vs 7.7+/-1.1 h/night; P=0.028). UARS women consumed significantly more prescription drugs than UARS men (P=0.017), and presented with a significantly lower quality of life score than their male counterparts (P=0.021). The quantitative snoring measure during sleep did not indicate significant gender differences between diagnostic categories and gender. CONCLUSIONS: Clinical presentation and polysomnographic parameters in patients with OSAS and UARS show distinct gender-related differences. These differences should be considered when patients present with signs and symptoms of OSAS or UARS.

Non-invasive estimation of esophageal pressure based on intercostal EMG monitoring.

Recording of esophageal pressure waveform is an important clinical tool to identify patients with sleep-disordered breathing. Commonly, esophageal pressure probes are not tolerated by patients undergoing sleep monitoring. We therefore developed a technique to non-invasively estimate esophageal pressure based on recording of intercostal EMG monitoring. A three step approach to modification of the intercostal EMG signal was created to closely match results obtained from esophageal pressure recording. The algorithm was then tested on 10 subjects with sleep-disordered breathing undergoing full polysomnography with simultaneous monitoring of esophageal pressure and intercostal EMG. Analysis of correlations between esophageal pressure and intercostal EMG were computed by sleep stages. The overall correlation coefficient in all subjects combined was r=0.896, p<0.00001. The results indicate that this method can be used reliably in clinical sleep studies where esophageal pressure recordings cannot be performed.

Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.

The efficacy of insulin in stimulating whole-body glucose disposal (insulin sensitivity) was quantified using direct methodology in thirty lacto-ovo vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23 kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4.1 (95 % CI 3.5, 5.0) v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo vegetarians had lower body Fe stores, as indicated by a serum ferritin concentration (microg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45, 100) for meat-eaters To test whether or not Fe status might modulate insulin sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels similar to that seen in vegetarians, with a resultant approximately 40 % enhancement of insulin-mediated glucose disposal Our results demonstrate that lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than meat-eaters. In addition, it seems that reduced insulin sensitivity in meat-eaters is amenable to improvement by reducing body Fe. The latter finding is in agreement with results from animal studies where, no matter how induced, Fe depletion consistently enhanced glucose disposal.

Sleep-disordered breathing and hypotension.

We investigated the presence of low blood pressure (BP) in 4,409 subjects referred for overnight polysomnography. A low resting arterial BP (systolic BP < 105 mm Hg, diastolic BP < 65 mm Hg) was present in 101 subjects (2.3%). Low BP was more prevalent in subjects with upper airway resistance syndrome (UARS) (23%) than in subjects with obstructive sleep apnea syndrome (OSAS) (0.06%), parasomnia (0.7%), restless leg syndrome (0.9%), or psychological insomnia (0.9%). In order to investigate BP homeostasis, we conducted polysomnography followed by tilt-table testing on 15 subjects with orthostatic intolerance (OI) and UARS, five normotensive subjects with UARS, five subjects with insomnia and low BP, 15 subjects with OSAS, and 15 healthy control subjects. Fifteen subjects with UARS and OI and 15 healthy controls also underwent 24-h ambulatory BP monitoring. Subjects with OI and UARS had lower mean daytime systolic (119 +/- 28 mm Hg) and diastolic (75 +/- 18 mm Hg) BP than did control subjects (131 +/- 35 mm Hg and 86 +/- 19 mm Hg, respectively) (p < 0.05). During tilt-table testing, subjects with UARS and a history of OI had a greater decrease in systolic BP (27 +/- 3 mm Hg) than did control subjects (7.5 +/- 1.6 mm Hg), subjects with OSAS (6.8 +/- 1.2 mm Hg), normotensive subjects with UARS (7.2 +/- 0.84 mm Hg), or hypotensive insomniacs (7.4 +/- 1.1 mm Hg) (p < 0.01). We conclude that approximately one fifth of subjects with UARS have low BP and complain of OI. Tilt-table testing may be indicated to confirm orthostatic intolerance in subjects with UARS.

[Obstructive sleep apnea syndrome: a cardiovascular risk factor?]. / Das obstruktive Schlafapnoe-Syndrom: Ein kardiovaskulärer Risikofaktor?

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is frequently associated with cardiovascular disease. We investigated endothelium-dependent and endothelium-independent nitric oxide-mediated vasodilatory function in normotensive patients with OSAS using the hand vein compliance technique. PATIENTS AND METHODS: Dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained in 23 male subjects with OSAS and 12 male control subjects of comparable age, height, and weight. RESULTS: Mean (+/- SD) maximum dilation (Emax) to bradykinin was significantly lower in OSAS patients than in controls (59.8 +/- 26.0 vs. 94.8 +/- 9.5%, p < 0.0001). Mean vasodilation with nitroglycerin was not diminished in the OSAS group (90.7 +/- 30.5 vs. 100.3 +/- 12.9% in controls; n.s.). In 11 OSAS patients, a follow-up investigation was performed after at least 2 months of treatment with nasal continuous positive airway pressure (CPAP): Emax to bradykinin rose from 54.5 +/- 19.2% to 111.5 +/- 25.1% after treatment (p < 0.001). Mean vasodilation to nitroglycerin was unchanged. CONCLUSIONS: These results suggest that endothelium-dependent nitric oxide-mediated vasodilation is impaired in patients with OSAS due to an impaired function in the endothelial cells. This impairment is reversible with CPAP treatment.

Misinterpretation of sleep-breathing disorder by periodic limb movement disorder.

We report a case of misinterpretation of sleep-disordered breathing due to periodic limb movement disorder. A 67-year-old man was diagnosed with sleep-disordered breathing and subsequently placed on treatment with nasal continuous positive airway pressure (CPAP). The initial diagnostic evaluation did not include measurement of anterior tibialis electromyogram. The respiratory disturbance index of the initial evaluation was 23. After a brief period of nasal CPAP use, the patient discontinued the treatment because no significant change in daytime alertness was noted and signs of CPAP-related insomnia appeared. The patient was restudied polysomnographically with monitoring of anterior tibialis electromyograms. This study identified 392 leg movements of which 65% were associated with brief EEG arousal from sleep. Double-blind analysis of respiratory disturbance and leg movements yielded a total number of 360 arousals in the overnight recording. Eighty-five percent of all respiratory events could be associated with central hypoventilation following periodic limb movement-associated EEG arousal. No significant hypoxia was recorded with these events. We hypothesize that chemoreceptor stimulation secondary to EEG arousal during sleep is responsible for this central hypoventilation. This case report highlights that recording and scoring of leg movements must be an integral part of polysomnographic evaluations.

Hyperinsulinemia: the missing link among oxidative stress and age-related diseases?

Mounting evidence supports Harman's hypothesis that aging is caused by free radicals and oxidative stress. Although it is known that oxidant species are produced during metabolic reactions, it is largely unknown which factor(s), of physiological or pathophysiological significance, modulate their production in vivo. In this hypothesis paper, it is postulated that hyperinsulinemia may have such function and therefore promote aging, independently of elevations of glycemia. Hyperinsulinemia is secondary to impaired insulin stimulated glucose metabolism at the level of skeletal muscle (insulin resistance) and is seen in about one third of glucose tolerant humans following dietary carbohydrate intake. If other insulin-stimulated (or inhibited) pathways retain normal sensitivity to the hormone, hyperinsulinemia could, by its effects on antioxidative enzymes and on free radical generators, enhance oxidative stress. Other proaging effects of insulin involve the inhibition of proteasome and the stimulation of polyunsaturated fatty acid (PUFA) synthesis and of nitric oxide (NO). The hypothesis that hyperinsulinemia accelerates aging also offers a metabolic explanation for the life-prolonging effect of calorie restriction and of mutations decreasing the overall activity of insulin-like receptors in the nematode Caenorhabditis elegans.

Vascular reactivity in obstructive sleep apnea syndrome.

The obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular disease and systemic hypertension. Because systemic arterial blood pressure is proportional to venodilation and venous return to the heart, we hypothesized that altered vascular responsiveness might exist in the veins of subjects with OSAS. We therefore investigated venodilator responses in awake, normotensive subjects with and without OSAS, using the dorsal hand vein compliance technique. Dose-response curves to bradykinin and nitroglycerin were obtained from 12 subjects with OSAS and 12 matched control subjects. Maximal dilation (E(max)) to bradykinin was significantly lower in the OSAS group (62.1% +/- 26.1%) than in the control group (94.3% +/- 10.7%) (p < 0.005). Vasodilation to nitroglycerin tended to be lower in the OSAS group (78.6% +/- 31.8%) than the control group (100.3% +/- 12.9%), but this effect did not reach statistical significance. When six of the OSAS subjects were retested after 60 d of treatment with nasal continuous positive airway pressure (CPAP), E(max) to bradykinin rose from 60.3% +/- 20. 3% to 121.4% +/- 26.9% (p < 0.01). Vasodilation to nitroglycerin also increased, but this effect did not reach statistical significance. These results demonstrate that a blunted venodilatory responsiveness to bradykinin exists in OSAS. This effect appears to be reversible with nasal CPAP therapy.

Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome.

BACKGROUND: Although sleep apnea is common, it often goes undiagnosed in primary care encounters. OBJECTIVE: To test the Berlin Questionnaire as a means of identifying patients with sleep apnea. DESIGN: Survey followed by portable, unattended sleep studies in a subset of patients. SETTING: Five primary care sites in Cleveland, Ohio. PATIENTS: 744 adults (of 1008 surveyed [74%]), of whom 100 underwent sleep studies. MEASUREMENTS: Survey items addressed the presence and frequency of snoring behavior, waketime sleepiness or fatigue, and history of obesity or hypertension. Patients with persistent and frequent symptoms in any two of these three domains were considered to be at high risk for sleep apnea. Portable sleep monitoring was conducted to measure the number of respiratory events per hour in bed (respiratory disturbance index [RDI]). RESULTS: Questions about symptoms demonstrated internal consistency (Cronbach correlations, 0.86 to 0.92). Of the 744 respondents, 279 (37.5%) were in a high-risk group that was defined a priori. For the 100 patients who underwent sleep studies, risk grouping was useful in prediction of the RDI. For example, being in the high-risk group predicted an RDI greater than 5 with a sensitivity of 0.86, a specificity of 0.77, a positive predictive value of 0.89, and a likelihood ratio of 3.79. CONCLUSION: The Berlin Questionnaire provides a means of identifying patients who are likely to have sleep apnea.

The snoring spectrum: acoustic assessment of snoring sound intensity in 1,139 individuals undergoing polysomnography.

STUDY OBJECTIVES: To quantify the snoring sound intensity levels generated by individuals during polysomnographic testing and to examine the relationships between acoustic, polysomnographic, and clinical variables. DESIGN: The prospective acquisition of acoustic and polysomnographic data with a retrospective medical chart review. SETTING: A sleep laboratory at a primary care hospital. PARTICIPANTS: All 1,139 of the patients referred to the sleep laboratory for polysomnographic testing from 1980 to 1994. INTERVENTIONS: The acoustic measurement of snoring sound intensity during sleep concurrent with polysomnographic testing. MEASUREMENTS AND RESULTS: Four decibel levels were derived from snoring sound intensity recordings. L1, L5, and L10 are measures of the sound pressure measurement in decibels employing the A-weighting network that yields the response of the human ear exceeded, respectively, for 1, 5, and 10% of the test period. The Leq is a measure of the A-weighted average intensity of a fluctuating acoustic signal over the total test period. L10 levels above 55 dBA were exceeded by 12.3% of the patients. The average levels of snoring sound intensity were significantly higher for men than for women. The levels of snoring sound intensity were associated significantly with the following: polysomnographic testing results, including the respiratory disturbance index (RDI), sleep latency, and the percentage of slow-wave sleep; demographic factors, including gender and body mass; and clinical factors, including snoring history, hypersomnolence, and breathing stoppage. Men with a body mass index of > 30 and an average snoring sound intensity of > 38 dBA were 4.1 times more likely to have an RDI of > 10. CONCLUSIONS: Snoring sound intensity levels are related to a number of demographic, clinical, and polysomnographic test results. Snoring sound intensity is closely related to apnea/hypopnea during sleep. The noise generated by snoring can disturb or disrupt a snorer's sleep, as well as the sleep of a bed partner.

Normative data on snoring: a comparison between younger and older adults.

Snoring is a common sleep-related behaviour. Increased body mass index (BMI), cranio-facial anatomical features, and older age have been linked to the occurrence of snoring. While mostly middle-aged populations have been studied for the occurrence of snoring and sleep-related breathing abnormality, this study was designed to assess the subjective report of snoring and the objective measurement of snoring at the two extremes of human age. The study design called for measurement of snoring in two age groups (college students; n=155 and older subjects; mean age 64.1 yrs n=134) with a mean age difference of 45 yrs. Snoring was assessed with a validated recording device. A validated questionnaire was used to subjectively assess snoring and obtain relevant sleep-related information. Students and older subjects differed in the self-report of snoring. While 83% of students reported "never" or "rarely" snoring only 35% of older subjects fell into these categories. Measurement of snoring during sleep revealed that students spent more time during sleep with continuous snoring than older subjects. In older subjects, a reduction in continuous snoring was accompanied by an increase in apnoeic snoring. Subjective snoring frequency correlated with continuous snoring in students only. A positive family history of snoring increased the odds ratio for self-reported snoring but not for recorded snoring. It has been shown that snoring frequency can vary depending on age and that the congruency between perceived snoring frequency and recorded snoring is influenced by the age of an individual.

Passive constriction of the upper airway during central apneas: fiberoptic and EMG investigations.

We studied five adult male patients with central sleep apnea syndrome (> 75% of the monitored events being central) during sleep using a fiberoptic scope and EMG monitoring of the superior and middle constrictors of the pharynx and the genioglossus and geniohyoid muscles. The fiberoptic investigation revealed a spontaneous decrease in the size of the airway during central apneas, without negative intrathoracic pressure or activation of the superior and middle pharyngeal constrictor muscles. We found a mean maximum decrease of 71 +/- 7% in the cross-sectional area of the airway and an absence of superior-middle pharyngeal constrictor EMG discharge. We did not observe any complete collapses of the airway.

A new tongue advancement technique for sleep-disordered breathing: side effects and efficacy.

We examined the efficacy and the acceptance of an oral device (SnorEx) causing a forward displacement of the tongue for the treatment of sleep-disordered breathing (SDB). Twenty-three consecutive subjects with SDB were investigated. Noncompliance (NC) of use of the oral appliance was observed in 74% (17 of 23) of the subjects. NC patients were characterized by unacceptable local side effects of the prosthesis, lacking improvement of indicators of daytime well-being, and a missing reduction of the respiratory disturbance index (RDI). The device was tolerated without side effects in 26% (6 of 23) of the subjects. In these compliant (C) subjects the RDI, EDS, and snoring improved significantly (p < 0.05) compared with baseline values. After 6 mo using the device, five of the six C patients were still using it. We conclude that the high rate of noncompliance and the low efficacy of the SnorEx prosthesis preclude large-scale use of this treatment modality in patients with SDB and snoring since the local side effects are the principal cause of NC. No useful predictive parameter of treatment compliance or treatment success was found. Thus, this dental appliance should be prescribed only for selected patients failing other treatment modalities seen by an experienced sleep-disorders specialist.

Sleep disordered breathing in primary care medicine.

Primary care medicine plays a key role in the delivery of health care. Sleep disorders medicine is a new specialty and standard medical school curricula do not contain any or only very little training in sleep medicine. Unrecognized and therefore untreated sleep disorders account for a large loss of human life and socio-economic damage. Recognition of sleep disorders, in particular sleep-disordered breathing at the primary care level is thus a major element in health care delivery. The objective of this study was to assess the occurrence of the risk of sleep-disordered breathing (SDB) in a large primary care population. 852 primary care patients received a validated questionnaire which contained items based on signs and symptoms of SDB, periodic limb movement disorder (PLMD), and insomnia. A polygraphically validated algorithm was used to identify patients with a high suspicion of having sleep disordered breathing. Based on this algorithm 20% of the study participants had a high risk for SDB, 18.5% of PLMD and 25% of insomnia.Most commonly daytime sleepiness and fatigue was associated in patients with a positive likelihood of SDB, PLMD, and insomnia. Fifty percent of all primary care patients reported to snore while 31% of snorers reported to snore every night. SDB was twice as common in men than in women and associated with a significantly higher body mass index. A popular validated scale to assess the degree of daytime sleepiness, the Epworth sleepiness scale, was not always useful to document the degree of daytime sleepiness.We conclude that SDB, PLMD, and insomnia are very frequent sleep disorders in primary care patients yielding the need to include assessment of these sleep disorders in the medical history of primary care physicians.

Should everyone be monitored for upper-airway resistance and how?

Preliminary data indicate that the use of a morphometric model, an expert system with standardized questions, and an evaluation of snoring can be effective tools for diagnosing upper-airway sleep-disordered breathing (UASDB) in many cases. This eliminates the need for many sleep recordings.

Sleep-disordered breathing and systemic hypertension in the older male.

OBJECTIVE: To investigate the relationship between sleep-disordered breathing (SDB) and essential hypertension in a population of older male hypertensives. PATIENTS: One-hundred forty consecutive older hypertensive males. MEASUREMENTS: Monitoring of sleep-related breathing abnormality with a portable sleep apnea monitor (level III device). Assessment of complaints related to sleep quality using a validated questionnaire. Systemic arterial blood pressure according to WHO standards and biochemical analyses. SDB was defined as more than 10 abnormal respiratory events per hour of sleep. DESIGN: Prospective investigation on a retrospective cohort. SETTING: Veterans Administrations hypertension clinic. MAIN RESULTS: SDB was diagnosed in 80% of this older, hypertensive, male population. Thirty-four percent of all study subjects presented with severe SDB, with more than 30 abnormal respiratory events per hour of sleep. Subjects with SDB were significantly heavier (BMI = 30.0 +/- 5.2 kg/m2) than subjects without SDB (BMI = 26.8 +/- 5.1 kg/m2, P = .004). Furthermore, subjects with SDB slept significantly longer (by a mean of 46 minutes/night, P = .027) and complained significantly more often of daytime sleepiness than subjects without SDB (P = .018). Fifty percent of all 140 subjects snored more than 10% of the total sleep time, and 26% snored for more than one-third of the night. No significant differences in blood pressure values were observed in subjects with compared with subjects without sleep-disordered breathing. However, a considerable number of subjects presenting with hypertensive blood pressure values despite treatment could be identified. Subjects presenting with hypertensive blood pressure values had a significantly higher severity index of SDB than subjects with normotensive blood pressure values (P = .047). CONCLUSIONS: This investigation supports data showing that undiagnosed SDB is a common phenomenon in older male individuals, leading to impaired daytime functioning and impairment of overall quality of life. More importantly, our data suggests that untreated SDB may have an adverse effect on the efficacy of antihypertensive treatment in hypertensive individuals with sleep-disordered breathing.

Enhanced sympathetic nervous system activity. The linchpin between insulin resistance, hyperinsulinemia, and heart rate.

This study was undertaken to see whether insulin resistant individuals, who are chronically hyperinsulinemic, have a higher heart rate (HR) than insulin sensitive, normoinsulinemic subjects. A total of 45 normotensive, nondiabetic individuals had insulin-mediated glucose disposal quantified by the insulin suppression test. In an effort to minimize variables known to modify heart rate, such as diet, exercise, and emotional distress, heart rate was continuously monitored during sleep by an electronic device measuring RR intervals. The average heart rate (as calculated by a mean of 30,720 +/- 208 beats per subject over a monitoring time of 6.9 +/- 0.6 h) was significantly related (r = 0.61; P < .001) to insulin resistance as expressed by the steady-state plasma glucose (SSPG) response to a continuous infusion of glucose, insulin and somatostatin and to the plasma insulin response to a 75 g of oral glucose challenge (r = 0.51; P < .001). These significant relationships between HR and both SSPG and plasma insulin response persisted after adjustment by stepwise regression analysis for age, gender distribution, body mass index, physical activity, and family history of either diabetes or hypertension. These results show that insulin resistant individuals, with compensatory hyperinsulinemia, have a higher nocturnal heart rate: a finding consistent with the possibility that the increased nocturnal heart rates are secondary to insulin-induced sympathetic activity.

Determinants of sleepiness in automobile drivers.

Governmental agencies do not systematically investigate the presence of daytime sleepiness as a determinant of driving accidents. We surveyed automobile drivers traveling on summer vacations and driving long distances on a European highway. We evaluated their subjective daytime sleepiness while driving and any sleep deprivation just prior to departure. Five-hundred sixty-seven automobile drivers (mean age 37.7 +/- 11 years) were interviewed at a roadside rest-stop. Questions covered the sleep/wake schedule during the year, sleep habits, and the presence of symptoms frequently associated with sleep-disordered breathing. Sleep behavior just prior to departure was compared to the usual sleep schedule during the year. Fifty percent of the responders had a sleep restriction just prior to departure (mean -203 minutes) compared to usual total sleep time during the year; 10% had no nocturnal sleep prior to departure. Drivers younger than 30 years were significantly more acutely sleep deprived than other drivers. Economic migrants (subjects with low economic status) also experienced significant acute sleep restriction.

Insulin resistance and sleep-disordered breathing in healthy humans.

Fifty healthy, normotensive individuals (34 women) with a mean age of 44.3 +/- 13.2 yr and a mean body mass index of 27.1 +/- 5.4 kg/m2 were tested for the presence or absence of insulin resistance and sleep-disordered breathing. The hypothesis of this investigation was that insulin resistance is associated with sleep-disordered breathing. In vivo insulin action with determination of steady-state plasma glucose (SSPG) and insulin was measured using simultaneous intravenous infusion of somatostatin, glucose, and insulin via a Harvard pump. Determination of sleep-disordered breathing was performed through clinical assessment and portable nocturnal monitoring using a validated sleep apnea recorder. Individuals with > or = 10 hypoxic respiratory events per hour of sleep were significantly more insulin-resistant than subjects without sleep-breathing disorders. After adjusting the relationship between insulin resistance and sleep-disordered breathing for potential confounding variables, it was found that this relationship was entirely dependent on body mass.