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.

[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.

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.

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.

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.

Sleep and sleep-disordered breathing in commercial long-haul truck drivers.

We have performed a study assessing the prevalence of sleep-disordered breathing in a large US trucking company using a validated portable monitor (MESAM-4) and a validated symptom questionnaire. Three hundred eighty-eight drivers with a mean age of 36 years filled out the questionnaire. One hundred fifty-nine drivers with a mean age of 35 years spent the night at the terminal hub where they underwent monitoring for identification of sleep-disordered breathing. The drivers also had blood pressure recorded while awake, seated, and after 15 min of quiet rest. Seventy-eight percent of the drivers had an oxygen desaturation index (ODI) > or = 5 per hour of sleep; 10% had an ODI > or = 30 per hour of sleep. There was a significant difference in the body mass index (BMI) between drivers with ODI < 5 and drivers with ODI > or = 5 (25.7 +/- 6.0 kg/m2 in drivers with ODI < 5 vs 29.0 +/- 6.3 kg/m2 in drivers with ODI > or = 5, p < 0.001). Sixteen percent of all drivers tested were hypertensive. Twelve percent were unaware of their hypertension. Hypertensive drivers were significantly more overweight (p < 0.0001), slept more restlessly (p < 0.04), took more naps (p < 0.03), and woke up more frequently during the night (p < 0.005). About 20% of drivers presented symptoms indicating very regular sleep disturbances. Drivers who had been with the company for more than 1 year were more likely to present daytime fatigue, daytime tiredness, unrestorative sleep, hypertension, and higher BMI. Long-haul truck drivers have very irregular sleep/wake schedules and a high prevalence of sleep-disordered breathing. Chronic sleep/wake disruption and partial, prolonged sleep deprivation may worsen sleep-disordered breathing. This combination of problems may impact significantly on the daytime alertness of truckers.

Traffic accidents in commercial long-haul truck drivers: the influence of sleep-disordered breathing and obesity.

This study assesses a possible independent effect of sleep-related breathing disorders on traffic accidents in long-haul commercial truck drivers. The study design included integrated analysis of recordings of sleep-related breathing disorders, self-reported automotive and company-recorded automotive accidents. A cross-sectional population of 90 commercial long-haul truck drivers 20-64 years of age was studied. Main outcome measures included presence or absence, as well as severity, of sleep-disordered breathing and frequency of automotive accidents. Truck drivers identified with sleep-disordered breathing had a two-fold higher accident rate per mile than drivers without sleep-disordered breathing. Accident frequency was not dependent on the severity of the sleep-related breathing disorder. Obese drivers with a body mass > or = 30 kg/m2 also presented a two-fold higher accident rate than nonobese drivers. We conclude that a complaint of excessive daytime sleepiness is related to a significantly higher automotive accident rate in long-haul commercial truck drivers. Sleep-disordered breathing with hypoxemia and obesity are risk factors for automotive accidents.