Dan Veale

Obstructive sleep apnoea and the autonomic nervous system

Understanding of the pathophysiology of obstructive sleep apnoea, a common yet relatively newly recognized condition, has advanced rapidly in recent years. This condition produces major acute haemodynamic changes and causal relationships with hypertension and cardiovascular morbidity have been proposed. The role that the autonomic nervous system plays in mediating these cardiovascular changes has been the focus of intensive research activity and the development of few techniques in physiological monitoring, such as spectral analysis of heart rate variability, Finapres blood pressure monitoring, measurement of muscle sympathetic nerve activity, radionuclide tests and animal models of obstructive sleep apnoea have substantially increased the knowledge base. The acute haemodynamic changes are associated with high levels of sympathetic discharge and with fluctuating parasympathetic activity. There are also chronic changes in baroreceptor and chemoreceptor reflexes associated with an increase in baseline daytime sympathetic activity and abnormal vagal reflex responses to voluntary respiratory manoeuvres. These acute autonomic changes appear to be provoked by a combination of stimuli triggered by hypoxaemia, upper airway responses, ventilatory changes and arousal. The mechanisms of the chronic autonomic changes are less clear; it is likely that recurrent hypoxaemia is important, but the roles of recurrent ventilatory stress and arousal are not clear. Normalizing respiration with CPAP therapy prevents the acute cardiovascular changes and reduces the acute sympathetic over-activity, and in compliant patients, restores abnormal vagal responses to normal and reduces excess chronic sympathetic activity. Whether or not this produces a reduction in long-term cardiovascular morbidity is not established.

Simultaneous laboratory-based comparison of ResMed Autoset with polysomnography in the diagnosis of sleep apnoea/hypopnoea syndrome

ResMed Autoset (AS) is a simplified diagnosis system for obstructive sleep apnoea/hypopnoea syndrome (OSAS) based on the respiratory flow/time relationship by pressure variation measured through simple nasal prongs. A multicentre prospective trial was used to compare AS and polysomnography (PSG) for diagnosing 95 patients, with suspected OSAS. Physicians gave a pretest probability of the patient having OSAS. The apnoea/hypopnoea index (AHI) was compared between the two methods of diagnosis for the whole population and for subgroups according to the pretest probability. Twenty-four patients had AHI < 15 events x h(-1) on PSG and 19 AHI 15-30, and 52 patients had AHI > or = 30. Correlation between AHI assessed by AS and PSG was r=0.87 for total sleep time (TST), p<0.0001. A Bland and Altman plot gave an agreement between the two methods of +/-40%. For a threshold of AHI > or = 15 events x h(-1) to diagnose OSAS, AS has a sensitivity of 92%, specificity of 79%, positive predictive value of 93% and negative predictive value of 76%. With a pretest probability > or = 80%, sensitivity and positive predictive value were 98 and 100% respectively. Of six false negative, four had a high pretest probability (> 80%) or Epworth score > or = 10. Using these parameters as a criterion for proceeding to PSG after a negative AS study would mean that two apnoeic patients (AHI 20 and 17 events x h(-1) by PSG) would escape detection. The Autoset is useful for the detection of obstructive sleep apnoea but with high pretest probability and a negative Autoset result polysomnography should be performed.

Cardiovascular risk factors in men and women with obstructive sleep apnoea syndrome

UNLABELLED We wished to evaluate the prevalence of cardiovascular (CV) risk factors in patients with obstructive sleep apnoea syndrome (OSAS) before initiation of continuous positive airway pressure (CPAP), and without any declared or diagnosed pre-existing CV disorder. We wanted to compare the prevalence of these CV risk factors between men and women in an observational study. A questionnaire concerning CV risk factors was submitted to the patients, by a respiratory home-care technician at the time of installation of the CPAP treatment. PATIENTS The study population consisted of 1117 patients; 834 men, 283 women. RESULTS The prevalence of arterial hypertension (HT), diabetes, obesity, active smoking, hyperlipidemia and family history of coronary heart disease was 54.1%, 22.8%, 65.8%, 18.3%, 33.8% and 20%, respectively. Women had significantly more HT (62.1 vs 51.4%), diabetes (29.9 vs 20.4%), obesity (77 vs 62%) and family history of coronary disease (25.1 vs 18.2%). The prevalence of active smoking was significantly higher in men (20.4 vs 12%). The prevalence of hyperlipidemia was not different between men and women (34.5 vs 31.8%). Stepwise logistic regression showed that HT and diabetes were both independently associated with BMI and age, while diabetes and not HT was independently associated with female gender. The prevalence of classical CV risk factors was very high in this population with OSAS requiring CPAP, especially in women. There is thus a very elevated CV risk level independent of that directly related to OSAS. It is important to screen for and treat classical CV risk factors in this population.

Circadian Changes of Left Ventricular Ejection Fraction in Normal Subjects

Sleep has a specific physiology with related cardiovascular changes. We have previously found in respiratory patients [chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (OSAS)] an unexpected decrease in left ventricular ejection fraction (LVEF) at waking in the morning when compared with the rest period during the day. Whether this observation was linked to the consequences of the respiratory abnormalities or reflected physiological fluctuations related to the changes in autonomic nervous system tone remained unknown. Thus, we have set out to analyze the changes in LVEF with sleep in normal individuals. Eight healthy young men had LVEF measured before and after submaximal exercise, at rest before bedtime, and on waking in the morning. Technetium-99m with in vivo red cell labelling was used. Sleep parameters were assessed using classical polysomnography. In order to detect any influence of autonomic nervous system stimulation on LVEF, sympathovagal tone (SVT) was also assessed during night-time LVEF measurements using spectral analysis of RR intervals. LVEF at rest was within the normal limits for all the subjects (range 51-62%). On submaximal exercise, the LVEF increased in four subjects, was unchanged in two, and decreased in two. The main result concerns the changes in LVEF overnight. In the morning, LVEF decreased dramatically in three subjects and reached a level of < 30% in four. These decreases in LVEF were not related to changes in SVT or sleep structure. LVEF values returned to normal in 30 min. The LVEF changes during exercise are in accordance with previous data in the literature. The dramatic decrease in LVEF observed in the morning could be related either to vascular resistance changes or to nocturnal variations in cardiac contractility, which both need further studies to be established.