OSA (obstructive sleep apnoea) is a common condition that is strongly associated with cardiovascular disease. It is remains unclear what role OSA plays in determining cardiovascular risk. The immediate physiological changes that occur during upper airway obstruction are potential contributors to cardiovascular risk in OSA. These changes include increased sympathetic activity, which is responsive to treatment of OSA with CPAP (continuous positive airway pressure). In this issue of Clinical Science , the possible role of a common polymorphism in the β 1 -adrenoreceptor [R389G (Arg389Gly)] has been investigated by Börgel and co-workers. Measurements of heart rate and blood pressure in untreated OSA patients were not related to the R389G polymorphism. There were changes in heart rate and diastolic blood pressure with CPAP treatment that were related to this polymorphism. Reduction in heart rate with CPAP treatment was associated with the R389R genotype. By contrast, a reduction in diastolic blood pressure was associated with the Gly 389 carriers. These findings are intriguing, but difficult to fully explain. Further study is needed to determine if there is an important role of the R389G polymorphism in modifying cardiovascular responses among OSA patients.

Sleep apnoea is associated with increased cardiovascular risk. Sleep apnoea is common after stroke and associated with increased blood pressure variability as described by Turkington and co-workers in this issue of Clinical Science . Both sleep apnoea and blood pressure variability confer a poor prognosis after stroke and are potentially treatable. Many studies of CPAP (continuous positive airway pressure) demonstrate decreases in cardiovascular risk markers in other patient groups. Although difficult to apply in these patients in the short term, CPAP has some potential benefits in medium-term rehabilitation and secondary prevention following stroke, which warrants further study.

Patients suffering from the obstructive sleep apnoea syndrome (OSAS) experience nocturnal episodes of upper airway obstruction resulting in recurrent oxygen desaturations and arousals. Methods to quantify the nocturnal obstructive events are of interest for characterizing this prevalent sleep disorder. In a study published in this issue of Clinical Science , Bloch and co-workers propose the computation of a new index for objectively quantifying the degree of flow limitation in patients with OSAS. The results obtained in a bench test and in a pilot study in patients suggest that the flow limitation index proposed may help to better characterize the disturbed breathing events undergone by patients with OSAS.

Sleep disordered breathing is common in patients with cerebrovascular disease, and could exacerbate the cerebral damage in acute stroke. Data about the effects of continuous positive airway pressure (CPAP) upon cerebral perfusion are conflicting. We investigated whether increasing levels of CPAP may affect cerebral haemodynamics, assessed by transcranial Doppler (TCD) in normal humans. A group of 25 healthy young volunteers were evaluated before (CPAP0-pre), during (CPAP5, CPAP10 and CPAP15, denoting CPAP at 5, 10 and 15 cmH 2 O respectively) and after (CPAP0-post) application of incremental levels of CPAP delivered through a mouthpiece. The mean cerebral blood flow velocity (CBFV) and the pulsatility index (PI; an indirect measure of cerebrovascular resistance) in the middle cerebral artery were measured with TCD. Respiratory rate, heart rate, end-tidal carbon dioxide pressure ( P ETCO 2 ), transcutaneous haemoglobin oxygen saturation ( S p O 2 ), mean arterial blood pressure and anxiety score were also recorded. Compared with CPAP0-pre, CBFV was significantly decreased as higher levels of CPAP were applied ( P <0.0001). CPAP15 increased PI ( P <0.05), P ETCO 2 was reduced by CPAP10 and CPAP15 ( P <0.0001), and anxiety score and S p O 2 increased at all levels of CPAP ( P <0.05). Heart rate, respiratory rate and mean arterial pressure did not change. The decrease in CBFV was correlated with the fall in P ETCO 2 (CPAP15) and the increase in PI (CPAP10, CPAP15) ( P <0.05). In conclusion, even low levels of CPAP delivered through a mouthpiece in awake, young volunteers led to a decrease in CBFV, measured by TCD. This fall in CBFV was associated with hypocapnia and with an increase in both cerebrovascular resistance and anxiety due to breathing against positive pressure. As the negative consequences of a fall in CBFV may outweigh the therapeutic effects of CPAP in the post-stroke setting, further studies of the cerebrovascular effects of CPAP with different interfaces in elderly patients with and without stroke are needed before intervention trials can be performed safely.

1. Inspiratory flow limitation is involved in the pathophysiology of sleep-related breathing disorders. Since the definition of flow-limited cycle is based on a dissociation between flow and respiratory efforts, identification of inspiratory flow limitation requires upper airway or intrathoracic pressure measurements. We examined the accuracy of the analysis of the flow—volume loop of a tidal breath in identifying inspiratory flow limitation during sleep in ten patients with a sleep apnoea—hypopnoea syndrome. 2. Measurements were taken during continuous positive airway pressure trials. After data acquisition, the presence of inspiratory flow limitation was identified by the presence of an inspiratory plateau or decrease in inspiratory flow independently of the increase in inspiratory efforts. The flow—volume loop was reconstructed for each breathing cycle by plotting the instantaneous flow and the tidal volume. The instantaneous inspiratory and expiratory flows were measured at 50% of the respective portion of the tidal volume, and a breath-by-breath analysis of the midtidal volume—flow ratio (inspiratory/expiratory ratio) was obtained. The analysis of the flow—volume loop was compared with standard inspiratory flow limitation criteria using different values of the inspiratory/expiratory ratio threshold, below which breathing cycles were classified as flow-limited. With a lower limit of the normal inspiratory/expiratory ratio threshold of 0.97, the sensitivity and specificity of the method were both 76%. In each subject, the proportion of breathing cycles identified as flow-limited according to the inspiratory/expiratory ratio progressively decreased with an increasing positive pressure level. 3. We conclude that analysis of the flow—volume curve is accurate in identifying most of the inspiratory flow limitation breathings in sleep apnoea—hypopnoea syndrome.

1. Continuous positive airway pressure increases intrathoracic pressure, thereby decreasing left ventricular preload and afterload. We hypothesized that there would be a dose-related alteration in cardiac and stroke volume indices in response to continuous positive airway pressure in normal subjects and patients with congestive heart failure and that the direction of response among those with heart failure would be related to left ventricular preload. 2. Cardiac and stroke volume indices were measured at baseline and after 10 min of continuous positive airway pressure at both 5 and 10 cmH 2 O (0.5 and 0.99 kPa respectively) in 16 patients with heart failure and five control subjects with normal cardiac function. Among the eight patients with heart failure and elevated pulmonary capillary wedge pressure (≧12 mmHg) (≦ 1.6 kPa), cardiac index increased from 2.47 ± 0.34 at baseline to 2.91 ± 0.32 to 3.12 ± 0.40 l min −1 m −2 ( P < 0.025) while on 5 and 10 cm H 2 O of continuous positive airway pressure respectively. In the same patients stroke volume index increased from 27.8 ± 3.9 to 33.9 ± 4.2 to 36.8 ± 5.5 ml/m 2 ( P < 0.05). In contrast, in both the control subjects and patients with heart failure and normal pulmonary capillary wedge pressure (< 12 mmHg) there was a dose-related decrease in cardiac and stroke volume indices while on continuous positive airway pressure. 3. Continuous positive airway pressure causes dose-related increases in cardiac and stroke volume indices among patients with chronic heart failure and elevated left ventricular filling pressure. However, it induces dose-related reductions in cardiac and stroke volume indices among normal subjects as well as patients with heart failure and normal left ventricular filling pressures.

1. Patients with obstructive sleep apnoea have increased diuresis during sleep, which decreases with nasal continuous positive airway pressure treatment. These changes have been attributed to an increased release of atrial natriuretic peptide in obstructive sleep apnoea, and its decrease with continuous positive airway pressure treatment. 2. In order to clarify the change in plasma atrial natriuretic peptide level and to investigate the underlying mechanisms, blood samples were taken at 10 min intervals from nine patients with obstructive sleep apnoea during two nights when the patients were either untreated or treated with continuous positive airway pressure. Polysomnographic monitoring, including transcutaneous oximetry, and measurement of oesophageal pressure were performed simultaneously. Plasma arginine vasopressin was also measured. 3. The plasma level of arginine vasopressin did not change. The level of atrial natriuretic peptide was high and exhibited secretion bursts in six out of the nine patients; it drastically decreased with continuous positive airway pressure treatment. 4. Across the patients, the mean plasma levels of atrial natriuretic peptide was correlated with the degree of hypoxaemia and the degree of oesophageal pressure swings during the sleep apnoeas. 5. Within the patients, cross-correlation studies suggested that the atrial natriuretic peptide secretory bursts were related either to the oesophageal pressure swings or to the apnoea-related hypoxaemia. 6. We conclude that release of atrial natriuretic peptide decreases with continuous positive airway pressure treatment in those patients with obstructive sleep apnoea who have increased release of atrial natriuretic peptide before treatment. 7. The results are in agreement with the hypothesis that the haemodynamic changes induced by the increased swings in intra-thoracic pressure during ineffective respiratory efforts or by the hypoxia-induced vasoconstriction play a role in these changes.