Snoring, not just a social nuisance

Snoring is a very common source of complaints from partners and neighbours. Snorers themselves are less likely to be affected, unless they have associated daytime sleepiness caused by the sleep disruption from obstructive sleep apnoea. There is increasingly firm evidence that obstructive sleep apnoea is associated with hypertension, cardiovascular, cerebrovascular and metabolic problems such as insulin resistance, even at mild levels which may not cause much daytime somnolence. In addition, the central and obstructive apnoeas found in cardiac failure affect heart muscle function. Treatment of the apnoea improves blood pressure and cardiac function and is likely to have a beneficial effect on mortality. Since obstructive sleep apnoea is common it should be sought by appropriate questioning in these patient groups. The treatments for obstructive sleep apnoea are effective but cumbersome and this remains a challenge if patients do not achieve obvious early benefits such as reduction in sleepiness or breathlessness.     

Heart rate variability during sleep and sleep apnoea in a population based study of 387 women

Increased sympathetic activity during sleep has been suggested as a link between obstructive sleep apnoea syndrome and cardiovascular disease. Heart rate variability (HRV) is a measure of autonomic effect on the heart. Different parameters have been associated with sympathetic and parasympathetic activity. We have studied HRV in different sleep stages and related the HRV‐pattern to sleep apnoea in a population‐based sample of 387 women. We investigated the HRV‐parameters standard deviation of all R‐R intervals (SDNN), root of the averaged square of successive differences (RMSSD), low frequency component (LF), high frequency component (HF), ratio of low frequency component to high frequency component LF/HF and VSAI [variation in sympathetic activity between rapid eye movement (REM) and slow wave sleep, defined as LF_REM?LF_SWS]. The HRV‐parameters were compared with the results of a full‐night polysomnography. Hourly incidence of obstructive episodes was used for classifying the subjects into four apnoea‐hypopnoea index (AHI)‐groups (<5, ≥5 and <15, 15–30 and >30 events). Individual sleep stages were analysed by pooling all recordings. Women with high AHI had higher heart rate and LF/HF ratio. In subjects with AHI >30, LF/HF ratio however dropped to same level as with AHI <5. Subjects with high AHI had low VSAI. Levels of SDNN, LF and LF/HF ratio during REM and light sleep were similar to wakefulness. In slow wave sleep the parameters decreased. In conclusion, moderately increased prevalence of obstructive apnoeas was associated with signs of higher sympathetic activity. High AHI was however associated with a HRV‐pattern suggestive of depressed sympathetic drive and lowered ability to increase it during REM.     

Obstructive sleep apnoea causes transient and sustained systemic hypertension

Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy.     

Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea

Computed tomography has been used to study the pharyngeal airway during tidal breathing in wakefulness and during obstructive apnoeas in Non-REM sleep in patients with obstructive sleep apnoea. In supine subjects, contiguous transverse 10 mm sections were taken perpendicular to the posterior pharyngeal wall with a 2.1 s scan time. Studies during wakefulness showed that the narrowest section of the pharyngeal airspace was in the region posterior to the soft palate and that the minimal airway cross-sectional areas were significantly reduced in the group of patients with obstructive sleep apnoea compared to the group of control subjects without obstructive sleep apnoea. The studies during sleep showed that in all patients, the airspace posterior to the soft palate was a site of obstructive apnoeas. The length of the obstructed segment varied between patients, extending below the level of the soft palate in half the patient group. Airway narrowing and obstruction was due to posterior displacement of the soft palate and the tongue in the majority of patients, although lateral displacement of the pharyngeal walls was also observed. No occlusion was observed in the laryngopharynx although there was narrowing of oro- and laryngopharyngeal apertures below the site of obstruction during obstructive apnoeas. The size of the oropharyngeal airspace during wakefulness did not predict the presence of airway occlusion below the level of the soft palate when asleep. The variability between patients in the site(s) of upper airway obstruction during obstructive apnoeas have important implications for the choice of appropriate treatment in patients with obstructive sleep apnoea.     

Arterial baroreflex buffering of sympathetic activation during exercise-induced elevations in arterial pressure.

Static muscle contraction activates metabolically sensitive muscle afferents that reflexively increase sympathetic nerve activity and arterial pressure. To determine if this contraction-induced reflex is modulated by the sinoaortic baroreflex, we performed microelectrode recordings of sympathetic nerve activity to resting leg muscle during static handgrip in humans while attempting to clamp the level of baroreflex stimulation by controlling the exercise-induced rise in blood pressure with pharmacologic agents. The principal new finding is that partial pharmacologic suppression of the rise in blood pressure during static handgrip (nitroprusside infusion) augmented the exercise-induced increases in heart rate and sympathetic activity by greater than 300%. Pharmacologic accentuation of the exercise-induced rise in blood pressure (phenylephrine infusion) attenuated these reflex increases by greater than 50%. In contrast, these pharmacologic manipulations in arterial pressure had little or no effect on: (a) forearm muscle cell pH, an index of the metabolic stimulus to skeletal muscle afferents; or (b) central venous pressure, an index of the mechanical stimulus to cardiopulmonary afferents. We conclude that in humans the sinoaortic baroreflex is much more effective than previously thought in buffering the reflex sympathetic activation caused by static muscle contraction.     

Sympathetic Neural Mechanisms in Human Cardiovascular Health and Disease

The sympathetic nervous system plays a key role in regulating arterial blood pressure in humans. This review provides an overview of sympathetic neural control of the circulation and discusses the changes that occur in various disease states, including hypertension, heart failure, and obstructive sleep apnea. It focuses on measurements of sympathetic neural activity (SNA) obtained by microneurography, a technique that allows direct assessment of the electrical activity of sympathetic nerves in conscious human beings. Sympathetic neural activity is tightly linked to blood pressure via the baroreflex for each individual person. However, SNA can vary greatly among individuals and that variability is not related to resting blood pressure; that is, the blood pressure of a person with high SNA can be similar to that of a person with much lower SNA. In healthy normotensive persons, this finding appears to be related to a set of factors that balance the variability in SNA, including cardiac output and vascular adrenergic responsiveness. Measurements of SNA are very reproducible in a given person over a period of several months to a few years, but SNA increases progressively with healthy aging. Cardiovascular disease can be associated with substantial increases in SNA, as seen for example in patients with hypertension, obstructive sleep apnea, or heart failure. Obesity is also associated with an increase in SNA, but the increase in SNA among patients with obstructive sleep apnea appears to be independent of obesity per se. For several disease states, successful treatment is associated with both a decrease in sympathoexcitation and an improvement in prognosis. This finding points to an important link between altered sympathetic neural mechanisms and the fundamental processes of cardiovascular disease.MI = myocardial infarction; MSNA = muscle sympathetic neural activity; OSA = obstructive sleep apnea; SA = sinoatrial; SNA = sympathetic neural activityThe sympathetic nervous system plays a vital role in the everyday lives of human beings. Sympathetic neural responses are essential to simple tasks such as changing posture. Movement from a supine or sitting position to an upright position requires complex adjustments in blood flow and blood pressure, and these adjustments are ultimately coordinated by sympathetic nerves in conjunction with parasympathetic modulation of heart rate. Without such adjustments, blood flow to the brain would fall below autoregulatory limits, and standing up would consistently cause syncope. Indeed, some persons with severe autonomic failure are unable to stand (or sometimes even to sit upright) without fainting.^1,2This article presents an overview of our current understanding of sympathetic neural mechanisms in human cardiovascular control. It focuses on measurements of sympathetic neural activity (SNA) that are obtained by microneurography, a technique that can directly measure the electrical activity of sympathetic nerves in intact, conscious human beings. During the past 3 decades, the information yielded by this technique has greatly increased our clinical and mechanistic understanding of sympathetic neural mechanisms in health and disease. Ongoing research using this technique continues to yield new insights into the pathophysiology of cardiovascular diseases, including hypertension, coronary artery disease, and heart failure, and into the cardiovascular risk associated with diseases such as obstructive sleep apnea (OSA) and obesity.     

Sympathetic neural mechanisms in obstructive sleep apnea.

Blood pressure, heart rate, sympathetic nerve activity, and polysomnography were recorded during wakefulness and sleep in 10 patients with obstructive sleep apnea. Measurements were also obtained after treatment with continuous positive airway pressure (CPAP) in four patients. Awake sympathetic activity was also measured in 10 age- and sex-matched control subjects and in 5 obese subjects without a history of sleep apnea. Patients with sleep apnea had high levels of nerve activity even when awake (P < 0.001). Blood pressure and sympathetic nerve activity did not fall during any stage of sleep. Mean blood pressure was 92 +/- 4.5 mmHg when awake and reached peak levels of 116 +/- 5 and 127 +/- 7 mmHg during stage II sleep (n = 10) and rapid eye movement (REM) sleep (n = 5), respectively (P < 0.001). Sympathetic activity increased during sleep (P = 0.01) especially during stage II (133 +/- 9% above wakefulness; P = 0.006) and REM (141 +/- 13%; P = 0.007). Peak sympathetic activity (measured over the last 10 s of each apneic event) increased to 299 +/- 96% during stage II sleep and to 246 +/- 36% during REM sleep (both P < 0.001). CPAP decreased sympathetic activity and blood pressure during sleep (P < 0.03). We conclude that patients with obstructive sleep apnea have high sympathetic activity when awake, with further increases in blood pressure and sympathetic activity during sleep. These increases are attenuated by treatment with CPAP.     

Continuous positive airway pressure increases heart rate variability in heart failure patients with obstructive sleep apnoea

Patients with heart failure or OSA (obstructive sleep apnoea) have reduced HF-HRV (high-frequency heart rate variability), indicating reduced cardiac vagal modulation, a marker of poor prognosis. CPAP (continuous positive airway pressure) abolishes OSA in patients with heart failure, but effects on daytime HF-HRV have not been determined. We hypothesized that, in patients with heart failure, treatment of coexisting OSA by CPAP would increase morning HF-HRV. In 19 patients with heart failure (left ventricular ejection fraction <45%) and OSA (>/=20 apnoeas and hypopnoeas/h of sleep), HF-HRV was quantified before and 1 month after randomization to a control or CPAP-treated group. In the control group (n=7), there were no changes in HF-HRV over the 1 month study during wakefulness in the morning. In the CPAP-treated group (n=12) HF-HRV increased significantly during wakefulness in the morning [from 2.43+/-0.55 to 2.82+/-0.50 log(ms(2)/Hz); P=0.002] due to an increase in transfer function between changes in lung volume and changes in HF-HRV (92.37+/-96.03 to 219.07+/-177.14 ms/l; P=0.01). In conclusion, treatment of coexisting OSA by nocturnal CPAP in patients with heart failure increases HF-HRV during morning wakefulness, indicating improved vagal modulation of heart rate. This may contribute to improved prognosis.     

Pharyngeal Size and Shape During Wakefulness and Sleep in Patients with Obstructive Sleep Apnoea

Computed tomography has been used to study the pharyngeal airwayduring tidal breathing in wakefulness and during obstructiveapnoeas in Non-REM sleep in patients with obstructive sleepapnoea. In supine subjects, contiguous transverse 10 mm sectionswere taken perpendicular to the posterior pharyngeal wall witha 2.1 s scan time. Studies during wakefulness showed that thenarrowest section of the pharyngeal airspace was in the regionposterior to the soft palate and that the minimal airway cross-sectionalareas were significantly reduced in the group of patients withobstructive sleep apnoea compared to the group of control subjectswithout obstructive sleep apnoea. The studies during sleep showedthat in all patients, the airspace posterior to the soft palatewas a site of obstruction during obstructive apnoeas. The lengthof the obstructed segment varied between patients, extendingbelow the level of the soft palate in half the patient group.Airway narrowing and obstruction was due to posterior displacementof the soft palate and the tongue in the majority of patients,although lateral displacement of the pharyngeal walls was alsoobserved. No occlusion was observed in the laryngopharynx althoughthere was narrowing of oro- and laryngopharyngeal aperturesbelow the site of obstruction during obstructive apnoeas. Thesize of the oropharyngeal airspace during wakefulness did notpredict the presence of airway occlusion below the level ofthe soft palate when asleep. The variability between patients in the site(s) of upper airwayobstruction during obstructive apnoeas have important implicationsfor the choice of appropriate treatment in patients with obstructivesleep apnoea.     

Pattern recognition of obstructive sleep apnoea and Cheyne-Stokes respiration

The aim of this study was to assess the validity of an artificial neural network based on flow-related spectral entropy as a diagnostic test for obstructive sleep apnoea and Cheyne-Stokes respiration. A data set of 37 subjects was used for spectral analysis of the airflow by performing a fast Fourier transform. The examined intervals were divided into epochs of 3 min. Spectral entropy S was applied as a measure for the spread of the related power spectrum. The spectrum was divided into several frequency areas with various subsets of spectral entropy. We studied 11 subjects with obstructive apnoeas (n = 267 epochs), 10 subjects with obstructive hypopnoeas (n = 80 epochs), 11 subjects with Cheyne-Stokes respiration (n = 253 epochs) and 5 subjects with normal breathing in non-REM sleep (n = 174 epochs). Based on spectral entropy an artificial neural network was built, and we obtained a sensitivity of 90.2% and a specificity of 90.9% for distinguishing between obstructive apnoeas and Cheyne-Stokes respiration, and a sensitivity of 91.3% and a specificity of 94.6% for discriminating between obstructive hypopnoeas and normal breathing in non-REM sleep. This resulted in an accuracy of 91.5% for identifying flow patterns of obstructive sleep apnoea, Cheyne-Stokes respiration and normal breathing in non-REM sleep. It is concluded that the use of an artificial neural network relying on spectral analysis of the airflow could be a useful method as a diagnostic test for obstructive sleep apnoea and Cheyne-Stokes respiration.     

Circulatory responses to stand up: discrimination between the effects of respiration,orthostasis and exercise

Summary. The initial circulatory responses to an active change in posture (stand up from supine) were compared with the responses induced by a passive change in posture (head-up tilt) and a burst of muscular exercise on a bicycle ergometer (upright cycling) in order to differentiate between exercise- and orthostasis-induced effects. In eight subjects heart rate responses and in four subjects intra-arterial pressure transients were measured. In addition the effects of respiration on heart rate responses to the three manoeuvres were assessed. Both stand up and cycling induced almost superimposable and pronounced heart rate responses lasting for about 30 s. This contrasts with the more gradual increases following head-up tilt. Changing the respiratory phase during the performance of the manoeuvres exerted its effect on heart rate responses in the first 5 s only. Like stand up, cycling induced a transient blood pressure fall lasting for 30 s on average. As both manoeuvres were performed during inspiration the transients observed are not caused by involuntary Valsalva straining. In conclusion, the maximum and duration of the heart rate responses induced by stand up, cycling and head-up tilt are not influenced by respiratory activity. The initial fall in blood pressure following stand up is probably the result of the muscular effort of the manoeuvre and not due to the effects of orthostasis or Valsalva straining.     

Effects of treatment with nasal continuous positive airway pressure on atrial natriuretic peptide and arginine vasopressin release during sleep in patients with obstructive sleep apnoea

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.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors associated with undiagnosed obstructive sleep apnoea in hypertensive primary care patients

Objective

In hypertensive primary care patients below 65 years of age, (i) to describe the occurrence of undiagnosed obstructive sleep apnoea (OSA), and (ii) to identify the determinants of moderate/severe OSA.

Design

Cross-sectional.

Setting

Four primary care health centres in Sweden.

Patients

411 consecutive patients (52% women), mean age 57.9 years (SD 5.9 years), with diagnosed and treated hypertension (BP >140/90).

Main outcome measures

Occurrence of OSA as measured by the apnoea hypopnoea index (AHI).

Results

Mild (AHI 5–14.9/h) and moderate/severe (AHI > 15/h) OSA were seen among 29% and 30% of the patients, respectively. Comparing those without OSA with those with mild or moderate/severe OSA, no differences were found in blood pressure, pharmacological treatment (anti-hypertensive, anti-depressive, and hypnotics), sleep, insomnia symptoms, daytime sleepiness, or depressive symptoms. Obesity (BMI > 30 kg/m2) was seen in 30% and 68% of the patients with mild and moderate/severe OSA, respectively. Male gender, BMI > 30 kg/m2, snoring, witnessed apnoeas, and sleep duration >8 hours were determinants of obstructive sleep apnoea.

Conclusion

Previously undiagnosed OSA is common among patients with hypertension in primary care. Obesity, snoring, witnessed apnoeas, long sleep duration, and male gender were the best predictors of OSA, even in the absence of daytime sleepiness and depressive symptoms.Key Words: Depression, hypertension, obstructive sleep apnoea, sleep, sleep disordered breathing, snoringCurrent awareness:

• Obstructive sleep apnoea has been linked to hypertension in sleep clinic populations, but there is a lack of knowledge regarding the occurrence in Swedish hypertensive primary care patients.

Main statements:

• Undiagnosed mild and moderate/severe obstructive sleep apnoea was seen among 29% and 30% of patients, respectively.
• Comparing subjects with mild or moderate/severe obstructive sleep apnoea with those without, no differences were found in blood pressure, self-rated sleep duration, insomnia, daytime sleepiness, or depressive symptoms.
• Male gender, BMI > 30 kg/m00B2, snoring, witnessed apnoeas, and sleep duration >8 hours were determinants of moderate/severe obstructive sleep apnoea in hypertensive primary care patients.

     

Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans.

Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829-1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P < 0.01), mean arterial pressure (P < 0.01), and blood glycerol concentration (P < 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea.     

Whole-body impedance recording--a practical method for the diagnosis of sleep apnoea

The aim of this study was to evaluate the utility of whole-body impedance cardiography (ICGWB) in sleep studies, particularly in sleep apnoea detection. A comparison between simultaneous whole night ICGWB and standard polysomnographic recordings were made in 14 patients with a clinical suspicion of obstructive sleep apnoea, a mean age of 46 years (range 30-63 years) and a mean BMI of 29 kg m-2 (25-47). Obstructive apnoeas, central apnoeas and hypopnoeas all caused characteristic patterns in the ICGWB tracing. For an apnoea-hypopnoea index (AHI) > 15 events h-1, the sensitivity of ICGWB was 89% and the specificity 80%. In conclusion, ICGWB signal includes valuable physiological information that can be effectively used for the detection of sleep apnoea episodes. The method seems promising in cases where the multichannel polysomnography is not applicable or when ICGWB is used for haemodynamic monitoring in seriously ill and postoperative patients.     

Muscle afferent and central command contributions to the cardiovascular response to isometric exercise of postural muscle in patients with mild chronic heart failure

The roles of muscle afferent activity and central drive in controlling the compromised cardiovascular system of patients with mild chronic heart failure (CHF) during isometric exercise were examined. Blood pressure and heart rate responses were recorded in eight stable CHF patients (ejection fraction 20-40%; age 62+/-11 years) and in nine healthy age-matched controls during voluntary and electrically evoked isometric plantar flexion and subsequent post-exercise circulatory occlusion (PECO). During voluntary contraction, control subjects had a greater mean increase in systolic blood pressure than patients (42.4+/-19.2 and 23.0+/-10.9 mmHg respectively; P<0.01), but this was not the case during PECO. During electrically evoked contraction, but not during PECO, the CHF group had smaller (P<0.05) mean increases in both systolic and diastolic blood pressure than controls (13.0+/-5.3 compared with 25.4+/-14.0 mmHg and 7.6+/-3.0 compared with 12.9+/-7.2 mmHg respectively). Intra-group comparison between responses to voluntary and electrically evoked contractions revealed greater (P<0.05) mean increases in systolic and diastolic blood pressure during the voluntary contraction in both the patients and the control subjects. These data suggest that muscle afferent drive to the pressor response from the triceps surae is low in this age group, both in control subjects and in CHF patients. Additionally, the patients may have a relatively desensitized muscle mechanoreceptor reflex.     

Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system.     

Adrenergic responses to sustained handgrip in patients with juvenile-onset-type diabetes mellitus.

1. The response of plasma noradrenaline, arterial blood pressure and heart rate to sustained handgrip at 30% of maximal voluntary contraction was studied in patients with long-term juvenile-onset-type diabetes millitus and healthy subjects of comparable age. 2. There was no significant difference between the intensity and duration of handgrip in diabetic patients and healthy subjects. 3. Sustained handgrip produced an increase in plasma concentration of noradrenaline both in diabetic and healthy subjects but the response in the diabetic subjects was significantly less. 4. The increase in systolic blood pressure during handgrip was significantly greater in diabetic subjects than in normal subjects. The increases in diastolic and mean blood pressure did not differ significantky. 5. The increase in heart rate during handgrip was greater in healthy subjects than in diabetic subjects. The response was smaller in diabetic patients with retinopathy than in the patients without retinopathy. 6. The sustained handgrip test may be useful for the diagnosis of abnormal sympathetic nervous system and haemodnynamic responsiveness in diabetic patients.     

Investigation into sleep disturbance of patients suffering from cluster headache

The new discoveries relating to cluster headache (CH) encouraged the study of the relationship of the hypothalamus to respiratory physiology and its comorbidity with sleep apnoea. The question is whether the apnoeas are more frequent during REM sleep and the desaturations could be involved as triggers of the cluster attacks. Furthermore, could the connection with the hypothalamus, already proved, be responsible for an alteration in the structure of REM sleep and a chemoreceptor dysfunction. We set out to analyse when polysomnography investigation is necessary in patients with CH. We studied 37 patients suffering from episodic CH, 31 (83.8%) men and six (16.2%) women. For the control group, we selected 35 individuals, 31 (88.6%) men and four (11.4%) women. There was a greater percentage of obstructive sleep apnoea (OSA) in patients with CH (58.3%) compared with the control group (14.3%) and with the general population (2-4%). In cases of pain during sleep, the majority is deflagrated during the REM phase, following a desaturation episode. A stratified analysis of the apnoea/hypnoea index relating to body mass index (BMI) and age showed that patients with CH have 8.4 times more chance of exhibiting OSA than normal individuals (P < 0001). This risk increases to 24.38 in patients with a BMI > 25 kg/m(2) and increases to 13.5 in patients > 40 years old. Surprisingly, the risk decreases sharply in patients with a BMI < 25 kg/m(2) and who are < 40 years old. Due to the fact that polysomnography is a complex, costly and sometimes difficult examination, we suggest, in concordance with the results, that it should be carried out routinely in patients with CH that exhibit a BMI of > 25 kg/m(2) and/or in patients who are > 40 years of age.     

What role do adrenoreceptor polymorphisms play in modifying cardiovascular responses in obstructive sleep apnoea?

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 beta1-adrenoreceptor [R389G (Arg389Gly)] has been investigated by B?rgel 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 Gly389 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.