CPAP reduces hypercoagulability, as assessed by thromboelastography, in severe obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality and hypercoagulability may be an underlying factor. We tested the hypotheses that patients with severe OSA are hypercoagulable and that two weeks of continuous positive airway pressure (CPAP) treatment reduces this hypercoagulability. In a prospective crossover study, twelve patients were randomized to either CPAP or no-CPAP for two weeks, a one week washout period, and then the other testing period for two weeks. Thromboelastography was used to assess coagulability at the start and end of each period and the apnoea-hypopnea indices (AHI) were measured at the end of each period. At baseline, ten patients had, compared to reference values, shorter clotting times, six increased rate of clot formation, twelve increased clot strength, and ten increased clotting indices. CPAP significantly reduced AHI (p=0.0003), clot strength (p=0.019) and clotting index (p=0.014). Hypercoagulability in patients with OSA can be detected by thromboelastography, and is reduced by CPAP.     

Ventilatory and cerebrovascular responses to hypercapnia in patients with obstructive sleep apnoea: effect of CPAP therapy

The purpose of this study was to assess whether the cerebrovascular response to hypercapnia is blunted in OSA patients and if this could alter the ventilatory response to hypercapnia before and after CPAP therapy. We measured the cerebrovascular, cardiovascular and ventilatory responses to hypercapnia in 8 patients with OSA (apnoea-hypopnoea index=101+/-10) before and after 4-6 weeks of CPAP therapy and in 10 control subjects who did not undergo CPAP therapy. The cerebrovascular and ventilatory responses to hypercapnia were not different between OSA and controls at baseline or follow-up. The cardiovascular response to hypercapnia was significantly increased in the OSA group by CPAP therapy (mean arterial pressure response: 1.30+/-0.16 vs. 2.04+/-0.36 mmHg Torr(-1); p=0.007). We conclude that in normocapnic, normotensive OSA patients without cardiovascular disease, the ventilatory, cerebrovascular, and cardiovascular responses to hypercapnia are normal, but the cardiovascular response to hypercapnia is heightened following 1 month of CPAP therapy.     

Cortico-motoneurone excitability in patients with obstructive sleep apnoea

A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.     

Effects of short-term CPAP withdrawal on neurobehavioral performance in patients with obstructive sleep apnea

STUDY OBJECTIVE: Changes in sleep parameters and neurobehavioral functioning were systematically investigated after an acute (1 night) and short-term (7 nights) period of withdrawal from continuous positive airway pressure (CPAP) treatment and 1 subsequent night of CPAP reintroduction in patients with obstructive sleep apnea. DESIGN: Repeated-measurement within-subject design. SETTING: Sleep laboratory, university teaching hospital. PARTICIPANTS: Twenty participants receiving optimal CPAP therapy for > or = 12 months. INTERVENTIONS: CPAP withdrawal. MEASUREMENTS AND RESULTS: Polysomnograms were performed on Night 0 (with CPAP), Night 1 and Night 7 (without CPAP) and Night 8_R (with CPAP). Acute CPAP withdrawal resulted in the recurrence of sleep-disordered breathing with sleep disruption, hypoxemia, and increased subjective sleepiness. Short-term CPAP withdrawal exacerbated hypoxemia, increased subjective and objective sleepiness and poor mood ratings. Neurobehavioral functioning assessed using the Psychomotor Vigilance Task was impaired following Night 7 and associated with hypoxemia and changes in morning levels of tumor necrosis factor-alpha. However, other neurobehavioral measures were not affected. Autonomic arousals measured via respiratory-related reductions in finger blood volume by peripheral arterial tonometry decreased from Night 1 to Night 7. On Night 8_R, reintroduction of CPAP treatment eliminated most airway obstruction, maintained oxygenation, and reversed daytime sleepiness and some vigilance decrements. CONCLUSION: Despite recurrence of sleep-disordered breathing with increased sleepiness and impaired vigilance, most neurobehavioral variables were unaffected by CPAP withdrawal. The reduction in vigilance appeared to be associated with worsened hypoxemia and changed levels of tumor necrosis factor-alpha. Resumption of CPAP treatment had immediate benefits on sleep consolidation and subjective sleepiness.     

Changes in dreaming induced by CPAP in severe obstructive sleep apnea syndrome patients

To study dream content in patients with severe obstructive sleep apnea syndrome (OSAS) and its modification with Continuous Positive Airway Pressure (CPAP) therapy. We assessed twenty consecutive patients with severe OSAS and 17 healthy controls. Polysomnograms were recorded at baseline in patients and controls and during the CPAP titration night, 3 months after effective treatment and 2 years later in patients. Subjects were awakened 5-10 min after the beginning of the first and last rapid eye movement (REM) sleep periods and we measured percentage of dream recall, emotional content of the dream, word count, thematic units, sleep architecture and REM density. Dream recall in REM sleep was similar in patients at baseline and controls (51.5% versus 44.4% respectively; P = .421), decreased to 20% and 24.3% the first and third month CPAP nights, and increased to 39% 2 years later (P = 0.004). Violent/highly anxious dreams were only seen in patients at baseline. Word count was higher in patients than in controls. REM density was highest the first CPAP night. Severe OSAS patients recall dreams in REM sleep as often as controls, but their dreams have an increased emotional tone and are longer. Despite an increase in REM density, dream recall decreased the first months of CPAP and recovered 2 years later. Violent/highly anxious dreams disappeared with treatment. A dream recall decrease with CPAP is associated with normalization of sleep in OSAS patients.     

Prolactin secretion during sleep in obstructive sleep apnoea patients

SUMMARY  Plasma prolactin (PRL) concentration exhibits a sleep-dependent pattern, with highest levels during sleep and lowest levels during the waking period. The syndrome of obstructive sleep apnoea (OSA) is associated with severe hypoxaemia and chronic sleep fragmentation, both of which could affect the sleep-entrained PRL rhythm. Treatment with nasal continuous positive airway pressure (CPAP) immediately restores a normal sleep structure by successful abolition of the apnoeas. In the present study, seven OSA patients underwent two night studies, once when no treatment was given and once during the first night of CPAP treatment. Sleep was recorded polygraphically in all experiments. Plasma PRL was measured at 10 min intervals and secretory rates were calculated by a deconvolution procedure. CPAP treatment greatly reduced hypoxaemia and improved sleep quality. The secretory pulse amplitude and the total amount of PRL secreted during the night remained constant regardless of whether patients were treated or not. The only difference found was a lower pulse frequency in untreated OSA patients as compared to treated patients, which may be attributed either to hypoxaemia or to sleep disturbance or to the combined action of both. Treatment may be considered to normalize PRL release by restoring pulse frequency to values similar to those observed for normal subjects.     

The effect of CPAP treatment on excessive daytime somnolence in patients with obstructive sleep apnea

The study was undertaken to investigate whether a CPAP therapy improves symptoms of excessive daytime sleepiness (EDS) in patients with obstructive sleep apnoea (OSA). In seventy six patients (66 M and 10 F) with AHI = 50 +/- 3.3, BMI = 34 +/- 0.9 kg/m2 and mean age = 50.4 +/- 1 years OSA was diagnosed using standard polysomnography. EDS was assessed using Epworth Sleepiness Scale (ESS). Each patient was examined two or three times, before, after 1 and/or 2-15 months of CPAP treatment. Significant reduction of EDS within 1 month of CPAP therapy was found. Mean ESS was reduced from 14.3 +/- 0.9 to 7.0 +/- 0.7 after 1 month therapy (p < 0.001). Continuation of treatment had no further effect on decrease of symptoms of daytime sleepiness. There was a correlation between percent of sleep spent with CPAP and improvement in ESS.     

Effect of nasal CPAP treatment on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea

Polycythaemia, peripheral oedema formation and hypertension have classically been described in association with obstructive sleep apnoea (OSA). However, there is very limited information about blood volume in OSA and how it changes during long-term treatment with nasal continuous positive airway pressure (nCPAP). Plasma (PV) and red-cell volumes (RCV), 24-h ambulatory blood pressure (BP), 24-h natriuresis and morning plasma aldosterone, renin activity and atrial natriuretic peptide in 11 men with a mean age of 47 y (range 37–55), apnoea index (AI) of 55 (22–106), body mass index of 36 (30–43) and seated BP of ≥140/90 mmHg without any medication were measured. BP-measurements were repeated after 3 weeks and all measurements after 3 mo of nCPAP treatment. Aldosterone and 24-h mean heart rates decreased during treatment. Twenty-four-h BP decreased after 3 weeks but that decrease did not persist after 3 mo of treatment. There was a relationship between changes in night-time mean BP and PV and aldosterone. The haematocrit declined in every patient. No significant changes were found in the mean PV or RCV. They were in all instances lower than has earlier been described for normal, non-obese subjects. These data also suggest that OSA causes divergent individual disturbances in blood volume homeostasis which can be corrected by nCPAP.     

Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: changes under nCPAP treatment

Nocturnal arousals are the essential cause of disturbed sleep structure in patients with obstructive sleep apnoea syndrome (OSAS). The aim of this study was to analyse the relationship between sleep stages, respiratory (type-R) and movement (type-M) related EEG arousals. Furthermore, the value of these arousals as a criterion for the efficiency of nCPAP treatment was estimated. We examined 38 male patients aged between 30 and 71 (49.1±20.9 SD) y. All patients suffered from OSAS. The mean respiratory disturbance index (RDI) was 47.3±27.8 per h. Polysomnographic monitoring was carried out on 4 subsequent nights: baseline night, 2 nights of nCPAP titration and nCPAP control night. Sleep was visually scored and EEG arousals were classified into type R and M, depending on whether changes of respiration or movement caused the arousal. The RDI, the R index (type-R/h), the M index (type-M/h) and the R and M indices in different sleep stages were calculated. During the baseline night a deficit of slow wave sleep (SWS) and REM sleep was found. Furthermore there were more type-R than type-M arousals registered (17.4 h^?1[3.6–43.6] vs. 5.9 h^?1[1.6–11.8]) ( P <0.01). They occurred during stages NREM 1, NREM 2 and REM ( P <0.01). An SWS sleep rebound and a reduction of the SWS and REM latencies were already found during the first CPAP night. The R index was reduced during the first CPAP night in all sleep stages ( P <0.01) and remained approximately the same in the following 2 nights (3. CPAP night: 1.1 h^?1[0.3–5.0]). Type M arousals occurred more in stages 1 and 2 ( P <0.01), and remained unchanged under nCPAP. We concluded that differentiation of nocturnal arousals may provide more detailed information regarding the influence of breathing disturbances on sleep. Respiratory related, not movement related, arousals may be a useful additional tool in judging the efficiency of OSAS.     

Therapy with noninvasive ventilation in patients with obstructive sleep apnoea: Effects on atherogenic lipoprotein phenotype

Patients with obstructive sleep apnoea are at increased risk of atherosclerotic morbidity and mortality. Abnormalities in lipid metabolism that occur in response to chronic intermittent hypoxia in patients with sleep-disordered breathing may increase the cardiovascular risk in an already susceptible population. Atherogenic lipoprotein phenotype and small, dense LDL have an independent predictive role for future cardio- and cerebro-vascular events in patients with the metabolic syndrome. Therefore, testing the hypothesis that therapy of obstructive sleep apnoea may reduce atherogenic lipoprotein phenotype might have significant clinical implications. We suggest that abolition of obstructive sleep apnoea by continuous positive airway pressure results in reductions in circulatory levels of small, dense LDL by improvements in oxygen saturation, reductions in oxidative stress, improvements in insulin sensitivity, and reductions in triglyceride biosynthesis. Testing the proposed hypothesis may contribute to improvements in clinical management of patients with obstructive sleep apnoea by early recognition of atherogenic dyslipidaemia followed by both, vigorous treatment of the underlying sleep-disordered breathing by noninvasive ventilation and targeted therapeutic modulation of hypertriglyceridaemia, low HDL-cholesterol and increased levels of small, dense LDL. Implementing this strategy to patients with obstructive sleep apnoea may potentially contribute to substantial reduction of their high cardiovascular risk.     

Increased sodium-proton antiporter activity in patients with obstructive sleep apnoea

Cytosolic pH (pH(i)) and the activity of the sodium-proton antiporter (Na(+)/H(+) antiporter) were measured in lymphocytes from 22 patients with obstructive sleep apnoea and from 24 age-matched healthy subjects (Controls). The cellular Na(+)/H(+) antiporter was measured spectrophotometrically using a pH-sensitive fluorescent dye after intracellular acidification using sodium propionate. Resting pHi was similar in lymphocytes from patients with obstructive sleep apnoea and from controls (7.36 +/- 0.20, n=22; vs. 7.35 +/- 0.19, n=24; mean +/- SD). The Na(+)/H(+) antiporter activity was significantly higher in patients with obstructive sleep apnoea than in controls (11.87 +/- 3.26 x 10(-3) pH(i)/s vs. 4.38 +/- 1.40 x 10(-3) pH(i)/s; P < 0. 0001). The apparent affinity of the Na+/H+ antiporter was not significantly different between the groups (6.90 +/- 0.23 vs. 6.87 +/- 0.20). In patients with obstructive sleep apnoea the activity of the Na(+)/H(+) antiporter remained stable during the night. The activity of the Na(+)/H(+) antiporter was 13.49 +/- 4.80 x 10(-3) pH(i)/s at 20.00 and 13.26 +/- 6.13 x 10(-3) pH(i)/s at 02.00. From the present results it is concluded that an increased cellular Na(+)/H(+) antiporter activity may be a genetic marker for patients who are predisposed to obstructive sleep apnoea.     

Effects of a cognitive-behavioural weight loss programme on overweight obstructive sleep apnoea patients

SUMMARY  Thirty-two obese patients (Body Mass Index (BMI) = 38.5 ± 3.7) with obstructive sleep apnoea (the average number of oxygen desaturations per hour of sleep exceeding 4% from the baseline (OD14) = 38.6 ± 23.9) underwent a one-year cognitive-behavioural weight reduction programme with a one year follow-up period.
The criteria for successful treatment were (i) a decrease in OD14 to less than 10 and (ii) a decrease in OD14 that was greater than 50%. Fourteen (44%) patients were considered to be treated successfully at six months. When the patients were grouped according to weight loss 23 patients had lost more than 5 kg; 12 (52%) of them belonged to the group treated successfully. At 24 months, however, only three (9%) patients could be regarded as treated successfully and six patients had been transferred to other treatment modes (Nasal Continuous Positive Airway Pressure (nCPAP) and uvulopalatopharyngoplasty (UPPP)). The changes in weight correlated with the changes in OD14 (r = 0.47 and 0.63 at the 6-month and the 24-month evaluation, respectively).     

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age-, sex- and education-matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n -back tasks were applied embedded in a reaction-time-decomposition approach. Deficits in n -back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1-back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2-back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross-group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.     

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).     

Clinical significance of ventricular late potentials in patients with obstructive sleep apnoea

SUMMARY  Patients with obstructive sleep apnoea (OSA) have an increased cardiovascular mortality and probably also an increased incidence of sudden cardiac death. Thus the question arises whether ventricular late potentials can constitute markers for an increased electric vulnerability in these patients. Signal-averaged electrocardiograms were recorded in 64 patients (6 female, 58 male; mean age 53.2 y) with OSA (mean apnoea-hypopnoea index (AHI) 41.7 h^-1 ± 24.3 h^-1). Furthermore, a continuous ambulatory electrocardiogram and gated radionuclide ventriculography were performed. Ventricular late potentials were recorded in 5 men out of 64 patients. Two of them had coronary artery disease (1 patient post-myocardial infarction), 2 hypertension, and 1 nocturnal hypertension. No correlation could be traced between left ventricular ejection fraction, severity and extent of ventricular premature beats, or severity of OSA and occurrence of ventricular late potentials. It was noticeable, however, that the patients with ventricular late potentials had severe OSA (mean AHI 50.2/h vs. 40.9/h). Although OSA may lead to structural myocardial changes that could be the basis for re-entrant circuits, ventricular late potentials were found in only 7.8% of these patients. The results of this study demonstrate that at present ventricular late potentials and signal-averaged electrocardiograms do not prove useful as screening methods for risk stratification of patients with OSA.     

Impairment of daytime cerebrovascular reactivity in patients with obstructive sleep apnoea syndrome

Several studies have demonstrated a clear association between snoring, sleep apnoea and increased risk of stroke. However, the possible role of sleep apnoea in the pathophysiogenetic mechanisms of cerebrovascular disease is still unknown. Our aim in this study was to investigate cerebral haemodynamic changes during the waking state in eight patients with sleep apnoea syndrome (OSAS) by means of transcranial Doppler (TCD). In particular, we studied cerebral vascular reactivity (CVR) to hypercapnia calculated by means of the breath holding index (BHI). The investigation was performed in the early morning, soon after awakening, and in the late afternoon. Data were compared with those of eight healthy subjects matched for age and vascular risk factors. OSAS patients showed significantly lower BHI values with respect to controls both in the morning (0.56 vs. 1.36; P < 0.0001) and in the afternoon (1.12 vs. 1.53; P < 0.0001). In patients, BHI values in the afternoon were significantly higher than in the morning ( P < 0.0001). These data demonstrate a diminished vasodilator reserve in OSAS patients, particularly evident in the morning. This reduction of the possibility of cerebral vessels to adapt functionally in response to stimulation could be linked to hyposensitivity of cerebrovascular chemoreceptors after the continuous stress caused by nocturnal hypercapnia.     

Pulmonary haemodynamics in obstructive sleep apnoea

SUMMARY  The time course of right ventricular output (RVO) and transmural pulmonary artery pressure (PAP) changes, detected beat-by-beat, were analysed in a sample of obstructive sleep apnoea (OSA) episodes recorded in six patients with OSA syndrome. RVO showed a trend to a decrease during apnoeas, due to a decrease in heart rate, and decreased further in the immediate post-apnoeic period, due to a decrease in right ventricular stroke volume [post-apnoeic RVO = 82.6 ± 9.3 (SD) % of the value in the immediate pre-apnoeic period; P <0.01]. Both systolic and diastolic transmural PAP showed a progressive increase throughout apnoeas (from 23.7 ± 7.3 to 29 ± 6.9 and from 9.1 ± 4.4 to 14.3 ± 3.3 mmHg, respectively, from early to late apnoeic period; P <0.01), and similarly high values in the late apnoeic and in the immediate post-apnoeic period. Therefore, cardiac output and arterial pressure in the pulmonary circulation undergo simultaneous inverse changes in OSA, similar to what was previously shown in the systemic circulation. Although these data cannot define accurately the behaviour of pulmonary vascular resistance, they suggest that pulmonary vascular resistance could also undergo continuous oscillations in OSA, with recurring peaks detectable between apnoea termination and the immediate post-apnoeic period.     

Circulating adrenomedullin in obstructive sleep apnoea

Adrenomedullin (AM) is a potent endothelial-derived vasodilator secreted under the influence of various stimuli such as hypoxia, shear stress and cytokines. As all of these stimuli might be active under the conditions of obstructive sleep apnoea (OSA), we hypothesized that vascular AM production is increased in these patients. The study included 41 consecutive OSA patients and 28 control subjects without sleep-disordered breathing who were recruited from a pool of patients hospitalized for other reasons. Both groups were matched for anthropometric and comorbid factors. In all patients, i.e. OSA and controls, peripheral venous blood samples were taken at 07:00 hours after diagnostic polysomnography. In subsets of OSA patients, this was repeated after two nights of continuous positive airway pressure (CPAP) therapy (n = 28) and after several months of constant CPAP use (n = 11). The controls and the untreated OSA patients did not have serial blood sampling. In all blood samples, plasma AM levels were measured by an enzyme immunoassay kit. At baseline, the OSA patients had markedly elevated AM concentrations when compared to the controls. There were no differences between normo- and hypertensive OSA patients. After two nights of CPAP therapy, AM levels significantly decreased. Patients on long-term CPAP treatment showed complete normalization of plasma AM concentrations. In conclusion, this pilot study suggests that circulating AM is increased in untreated OSA irrespective of coexistent arterial hypertension and declines after CPAP therapy. AM upregulation might be considered as an adaptive mechanism to counteract the emergence of OSA-related cardiovascular disease.