Hypertension and sleep apnoea

SUMMARY  Epidemiological data indicate a link between sleep-disordered breathing and elevation of arterial pressure. Previous studies suggest increased activity of the sympathetic nervous system in patients with sleep apnoea. The response of muscle sympathetic nerve activity was further investigated in normal, awake subjects following exposure to 20 minutes of asphyxia. Sympathetic nerve traffic increased during exposure and remained elevated even after the return to room air breathing. These findings raise the possibility that this sustained elevation of sympathetic nerve traffic could play a role in the development of daytime hypertension in patients with sleep-disordered breathing.     

Effects of the presence of hypertension on the relationship between obstructive sleep apnoea and sleepiness

Obstructive sleep apnoea (OSA) plays a significant role in increasing blood pressure. Significant decreases were reported in blood pressure of hypertensive OSA patients with sleepiness who underwent continuous positive airway pressure (CPAP) treatment, but not in non-sleepy hypertensive OSA patients. More recently, however, significant decreases in blood pressure in non-sleepy hypertensive OSA patients following CPAP were shown. Effects of sleepiness on hypertension in OSA patients have been investigated, but not the effects of hypertension on sleepiness in OSA patients. We investigated the relationships between hypertension and sleepiness in patients with OSA. We analysed data on 275 middle-aged male subjects from a cross-sectional epidemiological health survey. We measured blood pressure and sleep duration objectively using an actigraph for 7 days and the respiratory disturbance index (RDI) with a type 3 portable device for 2 nights, and assessed sleepiness using the Epworth Sleepiness Scale (ESS). The RDI correlated significantly with ESS scores in the 88 hypertensive subjects (r = 0.33, P = 0.0024), but not in the 187 non-hypertensive subjects (r = -0.01, P = 0.91). Short sleep duration correlated significantly with ESS scores in both groups. Both the RDI and short sleep duration were related independently to sleepiness in only hypertensive subjects. Furthermore, the RDI was related negatively significantly to sleep duration in hypertensive subjects. Although short sleep duration was related significantly to sleepiness in both groups, hypertension may be important for the sleepiness in OSA patients. Detailed mechanisms of the difference in the relationship between sleepiness and the severity of OSA with or without hypertension should be studied further.     

Effect of hypertension on upper airway function and sleep apnoea

SUMMARY  Current evidence suggests that elevations in blood pressure during obstructive apnoeic episodes increase pharyngeal collapsibility and the severity of obstructive sleep apnoea.     

Determinants of circadian blood pressure rhythm and blood pressure variability in obstructive sleep apnoea

SUMMARY  The prevalence of hypertension in patients with obstructive sleep apnoea (OSA) is high and blood pressure profile is characterized by nocturnal blood pressure (BP) elevation and increased nocturnal BP variability. Ambulatory 24-hour-biood pressure monitoring (ABPM) is a valid, non-invasive method to describe circadian BP variation. Circadian BP profile and nocturnal BP variability were related to OSA severity (apnoea-hypopnoea index, mean low O₂), age and body mass index (BMI) in 73 patients with OSA. Prevalence of hypertension was 75%, and in 59% BMI was greater than 30 kg m^-2. A nocturnal decline of at least 10% from daytime mean BP values (night/day BP ratio <0.9; dipper) was found in only 25% of hypertensive patients and 39% of normotensive patients. Comparison between dippers and non-dippers showed significant differences in apnoea severity (apnoea-hypopnoea index 32 + 19 vs. 50 + 23/h, P <0.01; mean low O₂ 84.5 + 4 vs. 80.2 + 5.8%, P< 0.01) but not for age and BMI. In multiple regression analyses with age, body mass index, apnoea-hypopnoea index and mean low O₂ as independent and BP ratios and BP variability as dependent variables, sleep apnoea severity was the only independent predictor for circadian BP rhythm and nocturnal BP variability. The results presented here suggest that independent of age and obesity the severity of sleep apnoea is an important determinant of circadian BP variation and nocturnal BP variability.     

Pulmonary artery pressure in sleep apnoea and snoring

SUMMARY  There is a renewed interest in pulmonary hypertension (PH) complicating obstructive sleep apnoea (OSA). The prevalence of PH in populations of patients with less severe OSA was documented to be around 10%. The most recent data from both catheterization and echocardiographic studies indicate that as many as 40% of patients with OSA have PH. It has been shown that non-obese patients with normal respiratory function tests can develop pulmonary hypertension. One of the other possible mechanisms involved may be the presence of heightened pulmonary artery pressure response to hypoxia. There are now data available to indicate that treatment with nasal CPAP can decrease or even normalize pulmonary artery pressure in patients with sleep apnoea.     

Arterial hypertension and sleep apnoea: effect of the angiotensin-converting enzyme (ACE) Inhibitor cilazapril on continuously measured blood pressure during sleep and wakefulness

SUMMARY  Male patients with arterial hypertension and obstructive sleep-related breathing disorders (mean age 50 y, Body Mass Index (BMI) 32.4 kg m^-2, Respiratory Disturbance Index (RDI) 47.2 and systolic/diastolic blood pressure (SBD/DBD) 162/103 mmHg) were examined before and after 8 days of treatment with the long-acting angiotensin-converting-enzyme (ACE) inhibitor cilazapril 2.5 mg vs. placebo in a double-blind design with parallel groups. Cardiorespiratory polysom-nography was carried out at night; during daytime wakefulness patients submitted to examinations of physical and mental exertion. Cilazapril reduced the mean pressure during the entire examination period (day and night) by 9.55 (SD±7.13) mmHg, compared to 4.57 (SD ±7.20) mmHg for placebo ( P < 0.006), independently from systematic changes of heart rate ( x = -3.3 and -3.5 bpm, respectively). During REM sleep, mean arterial pressure was significantly reduced by 8.63 (SD ±10.1) mmHg, compared to a reduction on placebo of 3.17 (SD 9.6) mmHg ( P = 0.023). Under psychometric strain, the mean arterial pressure was reduced by 15.31 (SD ±8.7) mmHg with cilazapril; under placebo medication by 6.19 (SD ±7.3) mmHg ( P < 0.0001). Heart rate was not significantly changed.     

Obstructive sleep apnoea as a risk factor for hypertension

SUMMARY  It is controversial whether obstructive sleep apnoea (OSA) is a risk factor for hypertension as previous reviews of the subject have emphasized the confounding effect of obesity. We examined evidence from recent studies to reassess this debate. Cross-sectional studies from sleep clinic population (Sydney Sleep Cohort, Gothenburg Sleep Clinic Cohort), community sample (Busselton Sleep Survey, Wisconsin Sleep Cohort) and obese population (Swedish Obese Subjects Study) provide stronger evidence that the relationship between sleep apnoea and hypertension is an independent one. Moreover recent studies looking at the effect of sleep apnoea treatment have demonstrated a fall in blood pressure independent of weight change. More definitive studies are required but recent data provide increasing evidence that OSA is an independent risk factor for hypertension.     

Prevalence of papilloedema in patients with sleep apnoea syndrome: a prospective study

The association of papilloedema (PO) with respiratory diseases and especially obstructive sleep apnoea (OSA) syndrome has been emphasised in many reports. The pathophysiology could rely on the episodic increase of intracranial pressure related to apnoeic episodes during night sleep. Nevertheless, prevalence of papilloedema in patient with OSA syndrome remains unknown. As this information could improve diagnosis and therapeutic strategies, the aim of the present study was to investigate the prevalence of PO in an OSA syndrome population. From 95 successive, recently diagnosed OSA patients, 35 answered a questionnaire about visual symptoms and underwent fundoscopic examination. Visual symptoms suggestive of PO were present in 40% of the patients, but none had PO. As a conclusion, PO does not seem to be frequently associated with OSA syndrome and systematic screening of PO in these patients does not seem to be warranted. Nevertheless, patients with visual complaints evocative of papilloedema should have their eye fundus checked since the association between OSA and PO exists. Further studies, including more patients, might be useful to establish which patients are at particular risk for this complication.     

The relationship between craniofacial anatomy and obstructive sleep apnoea: a case-controlled study

The aim of the study was to identify craniofacial and pharyngeal anatomical factors directly related to obstructive sleep apnoea (OSA). The design and setting was a hospital-based, case-controlled study. Ninety-nine subjects (78 males and 21 females) with a confirmed diagnosis of OSA, who were referred to the Dental Hospital for construction of a mandibular advancement splint were recruited. A similar number of control subjects, matched for age and sex, were recruited after completing snoring and Epworth Sleepiness Scale questionnaires to exclude habitual snoring and daytime sleepiness. An upright cephalogram was obtained and skeletal and soft tissue landmarks were traced and digitized. In OSA subjects the anteroposterior skeletal measurements, including maxillary and mandibular length were reduced (P < 0.001). The intermaxillary space was found to be 3.1 mm shorter in OSA subjects (P = 0.001). The nasopharyngeal airway in OSA subjects was narrower (P < 0.001) but pharyngeal length showed no difference. The tongue size was increased (P = 0.021), soft plate length, thickness and area were all greater (P < 0.001) and the hyoid bone was more inferiorly positioned in OSA subjects (P < 0.001). This study identifies a significant number of craniofacial and pharyngeal anatomical factors directly related to OSA.     

Influence of obstructive sleep apnoea on circadian blood pressure profile

SUMMARY  A high prevalence of systemic hypertension in obstructive sleep apnoea (OSA) has been described but data on circadian blood pressure (BP) profile are limited and give inconsistent results. The present study examines 24-h BP in 106 patients referred because of loud snoring or excessive daytime sleepiness in combination with snoring. Patients were classified as OSA ( n = 62) or habitual snorers (HS) ( n = 44). Respiratory disturbance index (RDI) in OSA was 47 ± 24 vs. 2 ± 2 in HS. Mean age and body mass index in OSA was significantly higher.
BP was measured non-invasively at 15-min intervals during a 24-h period. Daytime and night-time BP was higher in OSA compared to HS. BP night/day ratio in OSA was 0.92 ± 0.07 vs. 0.86 ± 0.06 in HS ( P < 0.05). To investigate the influence of variables other than breathing abnormalities during sleep on our results we compared BP profiles of 25 OSA and 25 HS matched for sex, age and body weight. Again differences in daytime and night-time BP and BP night/day ratio were significant. Using a value of at least 10% fall in nocturnal BP to describe a regular BP profile (dipper) 68% of OSA were classified as non-dippers vs. 24% of HS.
Influence of short-term (2–4 days) nCPAP therapy on circadian BP profile was investigated in 34 patients with OSA. Systolic and diastolic nocturnal (but not daytime) BP was significantly reduced. The percentage of non-dippers was 79% before and 50% after treatment. In conclusion results of this study indicate a causal link between OSA and abnormal circadian BP profile.     

Sleep-related sweating in obstructive sleep apnoea: association with sleep stages and blood pressure

The aim of this study was to investigate sleep-related sweating as a symptom of obstructive sleep apnoea (OSA). Fifteen otherwise healthy male non-smoking patients with untreated moderate-to-severe OSA underwent polysomnography, including measurements of skin and core body temperature and electrodermal activity (EDA) as an objective indicator of sweating. Evening and morning blood pressure was measured as well as catecholamines in nocturnal urine. All measurements were repeated after 3 months on successful continuous positive airway pressure (CPAP) treatment. The untreated OSA subjects had a mean (±SD) apnoea–hypopnoea index of 45.3 ± 3.9 and a mean EDA index during sleep of 131.9 ± 22.4 events per hour. Patients with higher EDA indices had higher systolic blood pressure in the evening and morning ( P  = 0.001 and 0.006) and lower rapid eye movement (REM) sleep percentage ( P  = 0.003). The EDA index decreased significantly to 78.5 ± 17.7 in the patients on CPAP treatment ( P  = 0.04). The decrease correlated with lower evening systolic and diastolic blood pressure ( P  = 0.05 and 0.006) and an increase in REM% ( P  = 0.02). No relationship was observed between EDA and skin or core body temperature, or to catecholamine levels in urine. OSA patients who experience sleep-related sweating may have increased blood pressure and decreased REM sleep compared with other OSA patients. CPAP treatment appears to lower blood pressure and increase REM sleep to a higher extent in these patients compared with other OSA patients.     

The value of one hour daytime sleep recording in the diagnosis of the sleep apnoea syndrome

In this study we investigated whether the diagnosis of sleep apnoea syndrome (SAS), based on night-time polysomnography (NPSG), can be predicted or excluded by a one-hour daytime polysomnography (DPSG). The results of 306 NPSGs were compared with DPSGs, which were performed the day before. Treated patients were excluded. In the 89 patients with SAS (Apnoea index (AI)>/=5) 59 showed apnoeas during the DPSG and 30 did not. In the 217 without SAS 25 showed apnoeas daring DPSG and 192 did not. Sensitivity for detecting SAS was 66%, the specificity was 88%, the positive predictive value (PPV) 70% and the negative predictive value (NPV) 86%. For relevant SAS (AI>/=10) the NPV would be 95%. We conclude that the one-hour DPSG is not sufficient for diagnosing or excluding SAS with certainty. It can be used to make the presence of relevant SAS unlikely.     

Intrathoracic pressure changes and cardiovascular effects induced by nCPAP and nBiPAP in sleep apnoea patients

SUMMARY  The effect of nasal continuous positive airway pressure (nCPAP) and nasal bi-level positive airway pressure (nBiPAP) on intrathoracic pressure and haemodynamics during wakefulness was studied in a group of nine patients with severe sleep apnoea. No patient took cardiovascular medication.
Patients were studied with a Swan Ganz catheter, an arterial line and an oesophageal balloon. nCPAP and nBiPAP were applied in the following pressure sequence: 5, 10 and 15 cm H₂O of CPAP and 10/5 and 15/10 cm H₂O of nBiPAP. Measurements were made at the end of a 5-min period at each pressure level. Intrathoracic pressure was noted to increase to a level of approximately 50% of the pressure delivered at the mask. At a CPAP of 10 cm H₂O and above, as well as at BiPAP of 10/5 or higher, there was a decrease in cardiac output (CO) and cardiac index (CI). CI fell below the normal value in two of the patients. Transmural pulmonary artery pressure (PPA_tm) decreased at a CPAP of 15 cm H₂O and at both BiPAP levels. Transmural right atrial pressure (PRA_tm) decreased at both BiPAP levels. There were no differences in CO, CI, PPA_tm and PRA_tm between nCPAP and nBiPAP at equal inspiratory pressures. SaO₂ increased during BiPAP 15/10 cm H₂O, whereas heart rate and arterial blood pressure did not change significantly. The data presented here are consistent with the literature on positive end-expiratory pressure (PEEP) applied via intratracheal tube and are likely to be due to a reduced venous return. It is concluded that nasally applied positive pressure may have acute negative effects on cardiac function in patients with sleep apnoea.     

Practicality of the Sleepstrip in postal screening for obstructive sleep apnoea

The SleepStrip, a disposable screening device for the detection of obstructive sleep apnoea (OSA), which displays an estimated apnoea-hypopnoea index (AHISS) was posted, with instructions, to 48 patients referred for sleep study for suspected OSA. The patients subsequently underwent a cardiorespiratory sleep study from which the AHIE was derived. Thirty patients (63%) returned the SleepStrip, the device displayed an AHISS in 22 patients (73%), of which 17 (57%) was deemed valid by the device. Twelve of the 30 patients who returned the SleepStrip had an AHIE > or = 20 on the detailed sleep study. Of these, the SleepStrip recording was valid in seven of which only two had an AHISS > or = 20. We concluded that the SleepStrip was not suitable for unsupervised postal screening for OSA.     

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.     

A dog model to investigate the relationship between obstructive sleep apnoea and blood pressure regulation

SUMMARY  Patients exhibiting obstructive sleep apnoea (OSA) do not display a normal circadian pattern of blood pressure. It is not clear whether this disruption of the circadian blood pressure pattern is a result of the intermittent airway obstruction during sleep or is the result of confounding factors, such as obesity and age, which are common in OSA and may independently affect blood pressure. To determine if a cause and effect relationship exists between repetitive airway obstruction during sleep and blood pressure regulation a chronically instrumented canine model of OSA has been developed. This canine model has been shown to reproduce the characteristic apnoea and hypersomnolence of human OSA. Furthermore, in this model a 12-h nocturnal period of repetitive airway obstruction during sleep caused an increase in baseline blood pressure of more than 10 mmHg that was sustained for at least two hours following the restoration of normal airway patency. These results imply that there is a cause and effect relationship between intermittent airway obstruction during sleep and elevated blood pressure.     

Regulation of blood volume—implications for cardiovascular pathophysiology in sleep apnoea

SUMMARY  Volume homeostasis plays an important role in the regulation of the cardiovascular system and maintenance of haemodynamics. The heart-kidney axis represents the central part of the volume regulating system: the heart senses changes in the volume status and influences renal function via neural and humoral pathways in order to compensate for disturbances in volume homeostasis and prevent under- or overfilling of the heart. An undisturbed circadian rhythmicity of volume homeostasis, renal function and secretory pattern of volume regulating hormones may be of physiological importance. Disturbances in volume regulation are involved in the pathogenesis of cardiovascular diseases, e.g. arterial hypertension and heart failure. Nocturia in sleep apnoea (suggesting heart failure) may be explained by changes in volume-regulating hormones indicating hypervolaemia of the central part of the cardiovascular system ('central hypervolaemia') caused by exaggerated venous return during repetitive Muller manoeuvres. Treatment of sleep apnoea abolishes nocturia and restores normal circadian rhythm of volume homeostasis and secretion of volume-regulating hormones. Chronic cardiac volume overload during sleep may be implicated in the pathogenesis of cardiovascular sequelae in sleep apnoea: cardiac hypertrophy and heart failure. Central hypervolaemia during sleep can cause long-term disturbances in blood pressure control by different mechanisms and may be in part responsible for the development of daytime hypertension in sleep apnoea. In summary, volume homeostasis is controlled by a complex interaction of heart and kidney. Disturbances may reflect cardiovascular diseases or may even be the cause. In sleep apnoea disturbances in volume regulation may be important for the development of cardiovascular sequelae.     

Autonomic markers of arousal during sleep in patients undergoing investigation for obstructive sleep apnoea, their relationship to EEG arousals, respiratory events and subjective sleepiness

Estimating the degree of sleep fragmentation is an important part of a respiratory sleep study and is conventionally measured using EEG micro arousals or is inferred indirectly from respiratory abnormalities such as apnoeas and desaturations. There is a need for less labour-intensive measures of sleep fragmentation, and transient rises in blood pressure and heart rate may fulfil this role. Forty unselected sleep clinic referrals undergoing investigation for possible obstructive sleep apnoea (OSA) were studied with one night of polysomnography. Three conventional indices of sleep fragmentation (EEG micro arousals, apnoea/hypopnoea index (AHI) and oxygen saturation dip rate (SaO₂ dips)) and two autonomic indices (heart rate and blood pressure rises) have been compared. Correlations between these five indices ranged from r=0.38 to r=0.73. Of the two autonomic indices, the correlations for blood pressure rises with SaO₂ dips and EEG micro arousals were stronger (r=0.71 and r=0.65, respectively) than those for heart rate rises (0.55 and 0.51). All indices of sleep fragmentation, apart from heart rate rises, were similar in their correlation with subjective sleepiness (r-values 0.21–0.36). Arousals implied from blood pressure rises (using pulse transit time) can be measured easily, are objective, and appear no worse at predicting subjective sleepiness than either EEG micro arousals or AHI. They may therefore provide a useful alternative to manual scoring of micro arousals from the EEG as an index of sleep fragmentation in sleep clinic patients undergoing investigation for possible OSA.