Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP). METHODS: Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), L-NMMA (a nitric oxide (NO) antagonist), and L-arginine (the substrate for NO). RESULTS: Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p<0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP v 278 (20)% before CPAP, p<0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by L-NMMA (p=0.05). L-Arginine reversed the effect of L-NMMA in all cases. CONCLUSION: In patients with OSA, treatment with CPAP improves baseline endothelial NO release and stimulates endothelium dependent vasorelaxation in the systemic circulation. This is a potential mechanism for improving systemic and vascular function in patients with OSA treated with CPAP.

Noninvasive pressure preset ventilation for the treatment of Cheyne-Stokes respiration during sleep.

Cheyne-Stokes respiration (CSR) during sleep is common in patients with congestive heart failure (CHF). This pattern of breathing fragments sleep, leading to daytime symptoms of sleepiness and fatigue. It was hypothesized that by controlling CSR with noninvasive pressure preset ventilation (NPPV), there would be a decrease in sleep fragmentation and an improvement in sleep quality. Nine patients (eight males, one female; mean +/- SD 65 +/- 11 yrs) with symptomatic CSR diagnosed on overnight polysomnography (apnoea/hypopnoea index (AHI) 49 +/- 10 x h(-1), minimum arterial oxygen saturation (Sa,O2, 77 +/- 7%) and CHF (left ventricular ejection fraction 25 +/- 8%) were studied. After a period of acclimatization to NPPV (variable positive airway pressure (VPAP) II ST, Sydney, NSW, Australia and bilevel positive airway pressure (BiPAP), Murraysville, PA, USA), sleep studies were repeated on therapy. NPPV almost completely abolished CSR in all patients with a reduction in AHI from 49 +/- 10 to 6 +/- 5 x h(-1) (p<0.001). Residual respiratory events were primarily due to upper airway obstruction at sleep on-set. Arousal index was markedly decreased from 42 +/- 6 to 17 +/- 7 x h(-1) (p <0.001). Sleep architecture showed a trend toward improvement with a reduction in stage 1 and 2 (79 +/- 7% during the diagnostic night versus 72 +/- 10% during NPPV, (p=0.057)), whilst sleep efficiency, slow-wave sleep (SWS), and rapid eye movement (REM) were not altered. Controlling Cheyne-Stokes respiration with noninvasive pressure preset ventilation resulted in reduced arousal and improved sleep quality in the patients with congestive heart failure. Noninvasive pressure preset ventilation should be considered a potential therapy for Cheyne-Stokes respiration in congestive heart failure in those patients who do not respond or fail to tolerate nasal continuous positive airway pressure therapy.

Is obstructive sleep apnoea a rapid eye movement-predominant phenomenon?

Obstructive sleep apnoea (OSA) is thought to be worse during rapid eye movement (REM) sleep. REM rebound in the late postoperative period can follow the REM suppression shown to occur after some types of surgery. This is thought to worsen nocturnal episodic hypoxaemia, leading to greater cardio-respiratory risk. We set out to determine if OSA was a REM-predominant phenomenon. We reviewed the sleep clinic records of 64 consecutive patients with a diagnosis of OSA on full overnight polysomnography and sufficient data to determine the presence of a sleep stage predominance. OSA was diagnosed if the number of apnoeas/hypopnoeas per hour of sleep, the respiratory disturbance index (RDI), was greater than 10. The variables recorded for the purposes of this study were the RDI and the minimum blood oxygen saturation using pulse oximetry (SpO2min) for both REM and non-rapid eye movement (NREM) sleep. All values are presented as mean (SD). The Wilcoxon signed rank test was used for statistical analysis. The means for NREM and REM RDI were, respectively, 36 (26) and 38 (27) per hour (P = 0.96). In 32 of the 64 patients (50%) the RDI in NREM was greater than in REM. Thirty-one (48%) had a larger number during REM. One patient had identical RDIs for both REM and NREM. Sixty-two patients had satisfactory pulse oximetry recordings for both NREM and REM, and the mean SpO2min values were, respectively, 84 (7) and 82 (13)% (P = 0.15). Twenty-nine patients (47%) had a lower SpO2min in REM (seven by more than 10% and two by more than 40%), while 24 (39%) were lower in NREM (two by more than 10%). Nine patients (14%) had identical values in REM and NREM. In contrast to suggestions that OSA is a REM-predominant phenomenon, this study suggests that respiratory disturbance is not greatly affected by sleep stage, in most patients. While a small number clearly desaturate much more during REM, the majority do not. Thus, postoperative REM rebound may worsen OSA in some patients, but in many it may do otherwise. The implications of postoperative sleep disturbance are therefore likely to be more complex than previously suggested.

Pre-eclampsia is associated with marked alterations in sleep architecture.

STUDY OBJECTIVES: Pre-eclampsia is currently the predominant cause of maternal and fetal morbidity and mortality. Diurnal blood pressure variation is flattened or reversed in pre-eclampsia; however, sleep has not been extensively investigated in this disease. Our objective was therefore to study sleep architecture in this group of patients. STUDY DESIGN: Full polysomnography using the Compumedics Sleepwatch System or Compumedics p-series. SETTING: NA. PATIENTS: 25 pre-eclamptic patients and 17 primigravidas with normal pregnancies and no history of cardiovascular disease or sleep disorder. With the exception of one subject, all pre-eclamptics were taking clonidine (a known suppressant of rapid eye movement-REM-sleep) for control of their hypertension. INTERVENTIONS: NA. RESULTS: Pre-eclamptic subjects had markedly altered sleep architecture, with a markedly increased percentage of time spent in slow-wave sleep (SWS) (21 * 2% versus 43 * 3%, p<0.001). There was a longer latency to rapid eye movement (REM) sleep (92 * 11 mins vs. 205 * 23 mins in control and pre-eclamptic subjects, respectively, p<0.001) and reduced time spent in REM (18 * 1% and 10 * 2% in control and pre-eclamptic subjects, respectively, p<0.001). CONCLUSIONS: While the increased REM latency and decreased REM time are most likely due to clonidine, this is unlikely to also account for the increased SWS. Two possible explanations for this include cerebral edema and release of cytokines, which are known to alter sleep structure.

Haemodynamic responses to obstructive sleep apnoeas in premenopausal women.

OBJECTIVES: Obstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses. DESIGN AND METHODS: Full overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (deltaBP) from pre- to post-apnoea termination was measured for each apnoeic cycle. RESULTS: Only 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (deltaMAP) 12 +/- 3 mmHg during the follicular phase and 20 +/- 3 mmHg during the luteal phase, P < 0.001; REM deltaMAP 11 +/- 3 mmHg during the follicular phase and 23 +/- 3 mmHg during the luteal phase, P < 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in non-ovulating subjects. CONCLUSIONS: Obstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.

Ventilatory control in patients with sleep apnoea and left ventricular dysfunction: comparison of obstructive and central sleep apnoea.

Sleep apnoea is common in patients with heart failure. While most patients have central sleep apnoea (CSA), a minority have obstructive sleep apnoea (OSA). The pathophysiology of CSA is not well understood. We hypothesized that central chemosensitivity would be an important pathophysiological factor in patients with CSA, and not in OSA. The aim of this study was to compare ventilatory responses between patients with CSA and those with OSA. Acute ventilatory responses to eucapnic hypoxia and hyperoxic hypercapnia were measured during wakefulness in 34 patients (33 males and one female, aged 59+/-8 yrs (mean+/-SD)), with stable medically-treated left ventricular dysfunction (LVD) and sleep apnoea (18 OSA and 16 CSA). Patients with CSA had a decreased awake end-tidal carbon dioxide tension (4.1+/-0.5 kPa), increased ventilatory response to carbon dioxide (0.65+/-0.43 L.min.(-1).kPa PCO2(-1)), and eucapnic hypoxic responses in the normal range (0.6+/-0.4 L.min(-1)/% fall in arterial oxygen saturation (Sa,O2)). In contrast, patients with OSA had normal end-tidal carbon dioxide tension (4.9+/-0.5 kPa), and normal ventilatory responses to hypercapnia (0.29+/-0.16 L.min(-1).kPa PCO2(-1)) and hypoxia (0.5+/-0.5 L-min(-1)/% fall in Sa,O2). These findings suggest that augmented chemosensitivity to hypercapnia may be an important factor in the pathophysiology of central sleep apnoea in patients with heart failure.

Aortic root dilatation in Marfan's syndrome: a contribution from obstructive sleep apnea?

We report two cases of Marfan's syndrome with coexistent obstructive sleep apnea (OSA) in which treatment with nasal continuous positive airway pressure was associated with attenuation of aortic root dilatation, a serious complication of the syndrome. We speculate that coexistent OSA promotes progressive aortic dilatation in some patients with Marfan's syndrome.

Hypercapnic blood pressure response is greater during the luteal phase of the menstrual cycle.

We investigated the cardiovascular responses to acute hypercapnia during the menstrual cycle. Eleven female subjects with regular menstrual cycles performed hypercapnic rebreathing tests during the follicular and luteal phases of their menstrual cycles. Ventilatory and cardiovascular variables were recorded breath by breath. Serum progesterone and estradiol were measured on each occasion. Serum progesterone was higher during the luteal [50.4 +/- 9.6 (SE) nmol/l] than during the follicular phase (2.1 +/- 0.7 nmol/l; P < 0.001), but serum estradiol did not differ (follicular phase, 324 +/- 101 pmol/l; luteal phase, 162 +/- 71 pmol/l; P = 0.61). The systolic blood pressure responses during hypercapnia were 2.0 +/- 0.3 and 4.0 +/- 0.5 mmHg/Torr (1 Torr = 1 mmHg rise in end-tidal PCO2) during the follicular and luteal phases, respectively, of the menstrual cycle (P < 0.01). The diastolic blood pressure responses were 1.1 +/- 0.2 and 2.1 +/- 0.3 mmHg/Torr during the follicular and luteal phases, respectively (P < 0.002). Heart rate responses did not differ during the luteal (1.7 +/- 0.3 beats.min-1.Torr-1) and follicular phases (1.4 +/- 0.3 beats.min-1.Torr-1; P = 0.59). These data demonstrate a greater pressor response during the luteal phase of the menstrual cycle that may be related to higher serum progesterone concentrations.

Sleep-disordered breathing and obesity.

Recent epidemiological data indicate that obstructive sleep apnoea (OSA) and related conditions are extremely common in the middle-aged population. Obesity is an important aetiological factor in sleep-disordered breathing with a multifactorial role in the pathogenesis of upper airway occlusion. One extreme of the spectrum of sleep-disordered breathing is obesity-hypoventilation syndrome (one type of OSA with awake respiratory failure). Sleep-disordered breathing has a number of clinical consequences, including excess cardiovascular morbidity. Obesity is an important confounder of this association. Treatment of these disorders has been revolutionized by the use of nasal continuous positive airway pressure (CPAP). Weight reduction reduces apnoea severity but is not curative in most obese patients with sleep apnoea.

Relationship between chemosensitivity, obesity and blood pressure in obstructive sleep apnoea.

It has previously been documented that patients with obstructive sleep apnoea (OSA) have an abnormal blood pressure (pressor) response to acute hypoxia when awake. The relationship between hypoxic chemosensitivity and 24 h blood pressure in OSA is not known. Twenty-four hour ambulatory BP (ABP) was measured at 15 min intervals for 24 h using a non-invasive device (Oxford Medilog ABP or Spacelabs 90207 recorder) in 49 men (mean age 51 +/- 9 years), with OSA. The BP response to acute hypoxia was measured either directly (radial arterial line) or indirectly (Finapress) during wakefulness. The pressor response to hypoxia (expressed as the slope of the regression line of mean BP on % fall in arterial oxygen saturation) was compared with the results of the ABP recording, sleep study data and clinical variables. A pressor response to acute hypoxia was present in all patients (mean 1.4 +/- 1.1 mmHg/% delta SaO2, range 0.1-4.5). There was a relationship between the magnitude of the pressor response to hypoxia, severity of sleep apnoea (RDI and minimum SaO2) and central obesity (waist measurement). In contrast, there was no relationship between BP response to hypoxia during wakefulness and 24-h BP. However, increasing obesity and severity of OSA were associated with loss of the normal fall in BP at night. We conclude that enhanced chemosensitivity is common in OSA but there is no demonstrable link between chemosensitivity and mean daytime or night-time ABP.

Determinants of prognosis in unstable angina.

The clinical prognostic indices in unstable angina pectoris, particularly recurrent rest pain, previous angina and diabetes, plus both transient and evolutionary T wave on the ECG during the admission period and either a positive stress test at low workload or a positive Holter monitor, identify a higher risk group. By the use of these noninvasive and clinical indices it is thus possible to stratify patients with unstable angina and may help in the management of this difficult condition.