The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis.

Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension. Increased angiotensin-converting enzyme (ACE) activity may be a possible promoting mechanism with different ACE insertion/deletion (I/D) genotypes influencing this activity. Studies investigating the association of ACE I/D polymorphisms with OSA have shown conflicting results. We aimed to undertake a meta-analysis of existing studies exploring the association of ACE I/D polymorphisms with the risk of OSA and hypertension. 10 studies were included in a random effects meta-analysis, comprising 1,227 OSA subjects and 1,227 controls. The effect size was measured using the odds ratio. The risk of having OSA in carriers of the D allele was 0.92 (95% CI 0.69-1.23). There was statistically significant heterogeneity across the studies (I(2)=42%, p=0.08 and I(2)=74%, p<0.0001 for genotype and allele frequency, respectively). The association of D allele frequency with the risk of OSA remained nonsignificant after stratification based on ethnicity, source of population sample, and the presence of hypertension. Subgroup analysis failed to show any influence of genotype and allele frequency on OSA severity. This meta-analysis revealed no association between the ACE I/D polymorphisms and OSA susceptibility.

Randomized controlled trial of variable-pressure versus fixed-pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).

STUDY OBJECTIVE: To determine whether fixed-pressure or variable-pressure CPAP was preferred by patients and gave better outcomes in patients with the obstructive sleep apnea/hypopnea syndrome (OSAHS). DESIGN: Randomized blinded cross-over trial with 6 weeks of fixed and 6 weeks of variable-pressure CPAP. SETTING: Sleep center. PATIENTS: 200 consecutive consenting CPAP naïve patients with daytime sleepiness and > 15 apneas + hypopneas/h after an attended auto-CPAP titration night. INTERVENTIONS: CPAP therapy using the same device (Autoset Spirit) set for 6 weeks in fixed pressure mode and for 6 weeks in variable pressure mode, the order of therapies being randomized. MEASUREMENTS AND RESULTS: All measurements were recorded at the end of each limb by a researcher blind to treatment. These included symptoms, Epworth Score, CPAP usage, objective sleepiness by modified Osler test, vigilance and health related quality of life. A total of 181 of 200 patients completed the study. At the end of the study, patients expressed no significant difference in the primary outcome, patient preference, 72 patients preferring fixed and 69 preferring variable-pressure CPAP. Epworth score was lower on variable (9.5, SEM 0.4) than fixed-pressure CPAP (10.0, SEM 0.3; P = 0.031). Mean CPAP use was higher on variable (4.2, SEM 0.2 h/night) than fixed-pressure CPAP (4.0, SEM 0.2 h/night; P = 0.047). There were no other significant differences between treatments. CONCLUSIONS This study shows no difference in patient preference and only a marginal benefit of variable over fixed-pressure CPAP in OSAHS in terms of subjective sleepiness and CPAP use. The clinical value of this difference remains to be determined. CLINICAL TRIAL INFORMATION: Variable-pressure versus fixed-pressure continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS); Registration # ISRCTN43085025.http://www.controlled-trials.com//SRCTN43085025.

Sleepiness and sleep-related accidents in commercial bus drivers.

INTRODUCTION: Professional drivers are at high risk of sleepiness due to a combination of factors including shift work and obstructive sleep apnea/hypopnea syndrome (OSAHS), and sleepiness in professional drivers is highly dangerous. This study aimed to determine the prevalence of excessive daytime sleepiness and accident rates in bus drivers. MATERIALS AND METHODS: Drivers employed at bus depots within 30 miles of Edinburgh were given a sleep questionnaire. One thousand eight hundred fifty-four drivers were approached, and 677 (37%; 25 female) completed questionnaires with a 97% response rate among the 456 given directly to drivers by the researcher. RESULTS: Of the responding drivers, 133 (20% of total, 19% of researcher-delivered questionnaires) reported an Epworth sleepiness score >10. Eight percent of drivers reported falling asleep at the wheel at least once/month, and 7% having an accident, and 18% a near-miss accident due to sleepiness while working. DISCUSSION: This study shows a concerningly high rate of sleepiness and sleep-related accidents among bus drivers. Screening for OSAHS among commercial drivers needs to be seriously evaluated with some urgency.

Mortality and morbidity in obstructive sleep apnoea-hypopnoea syndrome: results from a 30-year prospective cohort study.

BACKGROUND: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) carries substantial negative health consequences. This study examines factors affecting mortality and morbidity according to continuous positive airway pressure (CPAP) use and predictors affecting CPAP adherence in a longitudinal cohort of OSAHS patients. MATERIALS AND METHODS: This prospective, cohort study comprised 4502 patients who were diagnosed with OSAHS at a tertiary sleep disorders centre between 1982 and 2003. Of these, 1174 patients completed follow-up in 2012. Data collected included anthropometric, sleep and demographic characteristics, including comorbidities, ongoing medications and CPAP adherence. Patients were followed up for an average of 14.8±3.7 years. RESULTS: Imputation analysis showed that long-term CPAP users (>5 years) were 5.63 times more likely to be alive at study end than non-CPAP users (95% CI: 4.83-6.58, p<0.001) and 1.74-times more likely than short-term CPAP users (≤5 years) (95% CI: 1.49-2.02, p<0.001). Females had a significantly higher mortality rate during the follow-up period (26.8% versus 19.6%, p<0.001). Respiratory mortality was more common in patients with OSAHS, in particular those who did not use CPAP, compared to the general population (17.2% versus 12.2%, p=0.002 respectively), whereas deaths from cancer were less common compared to the general population (16.2% versus 25.6%, p<0.001). Compared to CPAP users, non-CPAP-users had a significantly increased incidence of type II diabetes mellitus (DMII) (27.9% versus 18.7%, p=0.003), ischaemic heart disease (IHD) (25.5% versus 12.7%, p<0.001) and myocardial infarction (MI) (14.7% versus 4.2%, p<0.001) at long-term follow-up. CONCLUSIONS: Long-term CPAP use in men and women with OSAHS reduces mortality and decreases the incidence of DMII and cardiovascular disease.

Multiblock modelling on the study of the kinetic degradation of rosuvastatin calcium in the presence of retention time shifts and rank deficiency.

In pharmaceutical development, forced degradation studies are mandatory before the commercialization of any drug product. They aim at identifying the possible degradation routes and the potential products that may be formed during drug product shelf life. The most widely used techniques for monitoring this in the pharmaceutical industry are hyphenated techniques such as Liquid Chromatography coupled to ultraviolet diode array detector (LC-DAD). There are however some drawbacks, such as long analysis times required for the elution of all compounds and coelution, which is not easily detected since degradation products usually have spectra very similar to that of the drug. Chemometrics methods applied to LC-DAD data are capable of solving this issue, but the approaches described in the literature first require peak alignment to solve the rank deficiency problem, which is a delicate preprocessing method for high order data. The present work describes another approach where extra information - the kinetic degradation profiles - is included for the modelling, generating a third-order data set for each sample, resulting in a four-way array (sample x retention times x spectra x degradation profile). This approach has the advantage of using the information in the third mode to solve the peak co-elution problem without the need for peak alignment among samples. With the proposed approach, it was possible to study the degradation of calcium rosuvastatin, a modern cholesterol lowering drug, using a 2 min-run, despite all the challenges in the modelling of this data. The proposed strategy was compared to an approach based on augmenting the matrix in the spectral/kinetic modes (second order modelling strategy).

Randomized clinical effectiveness trial of nurse-administered small-group cognitive behavior therapy for persistent insomnia in general practice.

STUDY OBJECTIVES: Persistent insomnia, although very common in general practice, often proves problematic to manage. This study investigates the clinical effectiveness and the feasibility of applying cognitive behavior therapy (CBT) methods for insomnia in primary care. DESIGN: Pragmatic randomized controlled trial of CBT versus treatment as usual. SETTING: General medical practice. PARTICIPANTS: Two hundred one adults (mean age, 54 years) randomly assigned to receive CBT (n = 107; 72 women) or treatment as usual (n = 94; 65 women). INTERVENTION: CBT comprised 5 sessions delivered in small groups by primary care nurses. Treatment as usual comprised usual care from general practitioners. MEASUREMENTS AND RESULTS: Assessments were completed at baseline, after treatment, and at 6-month follow-up visits. Sleep outcomes were appraised by sleep diary, actigraphy, and clinical endpoint. CBT was associated with improvements in self-reported sleep latency, wakefulness after sleep onset, and sleep efficiency. Improvements were partly sustained at follow-up. Effect sizes were moderate for the index variable of sleep efficiency. Participants receiving treatment as usual did not improve. Actigraphically estimated sleep improved modestly after CBT, relative to no change in treatment as usual. CBT was also associated with significant positive changes in mental health and energy/vitality. Comorbid physical and mental health difficulties did not impair sleep improvement following CBT. CONCLUSION: This study suggests that trained and supervised nurses can effectively deliver CBT for insomnia in routine general medical practice. Treatment response to small-group service delivery was encouraging, although effect sizes were smaller than those obtained in efficacy studies. Further research is required to consider the possibility that CBT could become the treatment of first choice for persistent insomnia in primary healthcare.

Effects of sleep fragmentation on the arousability to resistive loading in NREM and REM sleep in normal men.

STUDY OBJECTIVE: In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. DESIGN: Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. PARTICIPANTS: Sixteen healthy men aged 20 to 29 years. INTERVENTIONS: In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. MEASUREMENTS AND RESULTS: During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. CONCLUSIONS: Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.

Comparison of CPAP titration at home or the sleep laboratory in the sleep apnea hypopnea syndrome.

STUDY OBJECTIVES: Continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS) is conventionally started after in-laboratory overnight titration. This use of sleep laboratory space is both costly and limits access for diagnostic studies. This study aimed to evaluate whether automated CPAP titration in the home produced patient outcomes equal to those following laboratory-based automated CPAP titration. The main outcomes were Epworth Sleepiness Scale score, objective daytime sleepiness (Oxford SLEep Resistance test or OSLER test), and CPAP use; we also performed quality-of-life questionnaires: Functional Outcomes of Sleep Questionnaire and SF-36. DESIGN: Prospective, randomized, single-blind, parallel-group, controlled trial SETTING: Regional sleep center and patients' homes. PATIENTS: Two hundred CPAP-naïve patients with OSAHS requiring CPAP treatment. INTERVENTIONS: One hundred patients were randomly assigned to a standard 1-night in-hospital CPAP titration and 100 to 3 nights' home CPAP titration and then issued with fixed pressure CPAP. Data were analyzed on an intention-to-treat basis. MEASUREMENTS AND RESULTS: The patient groups did not differ at baseline. The CPAP pressures defined at titration (mean+/- SEM: 10.6+/-0.2, 10.4+/-0.2 cm H20, p = .19), number of mask leaks, and initial acceptance rates were similar in the sleep-laboratory and home-titrated groups. At 3-month follow-up, there was no significant difference in CPAP use (mean+/-SEM: 4.39+/-0.25, 4.38+/-0.25 h/night; p > .9), Epworth Sleepiness Scale score (9.5+/-0.5, 8.5+/-0.5, p = .14), OSLER, Functional Outcomes of Sleep Questionnaire, or SF-36 between the sleep-laboratory and home-titrated groups. CONCLUSIONS: Home-based automated CPAP titration is as effective as automatic in-laboratory titrations in initiating treatment for OSAHS.

A cephalometric comparison of patients with the sleep apnea/hypopnea syndrome and their siblings.

STUDY OBJECTIVES: To define differences in the skeletal components of facial structure predisposing to the obstructive sleep apnea/hypopnea syndrome (OSAHS) by a comparison of the craniofacial complex between people with OSAHS and their siblings without OSAHS. DESIGN: Case-control study using sibling pairs. SETTING: Scottish Sleep Centre. PARTICIPANTS: 104 patients with OSAHS living in Scotland and 107 of their siblings. INTERVENTIONS: All subjects had sleep studies, clinical review, and cephalometry performed. All measurements were scored blind to index or control status. MEASUREMENTS AND RESULTS: 207 cephalograms were available for analysis, of which 145 were for dentate subjects (90 with definite OSAHS; 55 without). In the dentate subjects, regression analysis (correcting for body mass index and age) showed OSAHS was associated with a significantly longer distance from the hyoid bone to the mandibular plane in men (P = .02) and in women (P = .036). Regression analysis in 22 pairs of dentate brothers, discordant for the diagnosis of OSAHS (controlling for age and body mass index), showed a shorter mandibular corpus (P = .013) and lower hyoid in relation to the mandibular plane (P = .006) to be significantly associated with a diagnosis of OSAHS. CONCLUSIONS: Men and women with OSAHS have a lower-set hyoid bone than do those without OSAHS. This occurs independently of obesity and remains even when intersubject variance is minimized by performing pairwise comparison of the craniofacial complex between siblings with and without OSAHS.

Acoustic reflection for nasal airway measurement in patients with obstructive sleep apnea-hypopnea syndrome.

STUDY OBJECTIVE: To measure nasal dimensions and explore relationships between these and patients' use of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: Prospective single-blind study. SETTING: A tertiary-care, sleep disorders referral center. PATIENTS: Sixty OSAHS patients (52 men, mean age 51 years, body mass index (BMI) 36.1 +/- 9.4 kg/m2). MEASUREMENTS: After in-vitro validation, acoustic reflection was used to measure the nasal minimal cross-sectional area (MCSA), mean area, and volume in OSAHS patients receiving CPAP treatment. Variables from sleep studies included the apnea-hypopnea index (AHI), titration pressure, and CPAP use (hours per night) after 3 months. Median MCSA was used to categorize subjects into small and large MCSA groups. Correlation and regression analyses were conducted to investigate the relationship between results of polysomnography and nasal acoustic reflection. RESULTS: At baseline the small and large MCSA groups were not different (P > .05) in BMI, age, mask type, or previous nasal stuffiness, but there were more women in the smaller MCSA group (P = .02). CPAP use was significantly lower in the small MCSA group (P = .007), but apnea-hypopnea index and titration pressure were indistinguishable between the 2 groups. Furthermore, CPAP use correlated significantly and positively with MCSA (r = 0.34, P = .008), mean area (r = 0.27, P = .04), and volume (r = 0.28, P = .03). Step-wise multiple regression models revealed that MCSA was a predictor of the CPAP compliance (R2 = 0.16, P = .002), and MCSA (P = .001) and age (P = .04) were predictive factors of CPAP compliance (R2= 0.22). Nasal dimensions were not related to subjective nasal stuffiness. CONCLUSIONS: CPAP use in patients with smaller nasal passages was lower than in those with larger passages. Objective measurement of nasal dimension may be more reliable than subjective self-report of nasal symptoms in identifying patients with OSAHS who might struggle with CPAP therapy.

Sleep complaints: snoring and daytime sleepiness in pregnant and pre-eclamptic women.

BACKGROUND AND PURPOSE: To examine whether snoring and sleepiness are linked in pregnancy and pre-eclampsia. PATIENTS AND METHODS: We recruited 167 healthy and 82 pre-eclamptic women in the third trimester of pregnancy and 160 non-pregnant women. Subjects and their partners completed a sleep questionnaire. Height, weight, neck circumferences and blood pressure were recorded for all. RESULTS: Pregnant and pre-eclamptic women were (mean +/-SD) 36+/-3.6 and 36+/-3 weeks pregnant, respectively. Age and height did not differ significantly between groups (P>0.2), but pre-eclamptic women were heavier than pregnant and non-pregnant women and had higher BMI than pregnant women before pregnancy (all P<0.05). Thirty-two percent of control, 55% of pregnant and 85% of pre-eclamptic women snored (P<0.001), but pre-pregnancy snoring rates (pre-eclamptic=36%, healthy pregnant women=27%) were similar to those in non-pregnant women (32%) (P>0.7). Sleepiness was reported by 12% of non-pregnant, 23% of pregnant and 15% of pre-eclamptic women (P<0.04), but non-pregnant women had lower mean Epworth Sleepiness scores than both pregnant and pre-eclamptic groups (P<0.001). Snoring was correlated with (P=0.002), but explained only <2%, of the variance in sleepiness. CONCLUSION: Snoring and sleepiness increased in the third trimester of pregnancy, particularly in patients with pre-eclampsia. However, the study suggests that sleepiness in pregnancy is largely due to factors other than snoring or breathing pauses.

Clinical audit of subjects with snoring & sleep apnoea/hypopnoea syndrome fitted with mandibular repositioning splint.

Snoring and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are often treated with mandibular repositioning splints (MRS), but the efficacy and satisfaction of them has not been comprehensively addressed. A survey on the use of and satisfaction with MRS was posted to 177 patients referred by a hospital orthodontic department for custom-fitting of a MRS. Data were analysed using non-parametric techniques. The response rate was 81% (n=144). Responders (30F, 114M) had mean (SD) age of 51 (11) years, apnoea+hypopnoea index (AHI) of 24 (21) per hr and Epworth Score of 10 (5) at diagnosis, and had been supplied with their MRS a median 7 (IQR 5-11) months previously. Fifty of the 144 patients (35%) had been offered continuous positive airway pressure (CPAP) treatment but had declined or abandoned this. Self-reported MRS use was 5 (2) h/night, with 74 of the 144 patients (51%) continuing to use MRS at least occasionally at a median 7 months after fitting. Survival analysis showed 12% still using MRS at 12 months. Epworth score fell slightly with MRS therapy [-2.4 (3.5); P=0.005] and 7 daytime and 2 nocturnal symptoms improved in MRS users (all P<0.05). Marital satisfaction did not change with MRS. Problems preventing MRS use in 70 non-users included: non-retention (n=12), sore mouth (n=13) or jaw (n=7), difficulties falling asleep (n=10) or breathing (n=7), excessive salivation (n=4), dental damage (n=4) and other problems (n=3). Continued use of MRS therapy was associated with a higher number of teeth, low marital satisfaction perceived by partners and greater improvement in symptoms reported by patients and partners. Continuance with MRS may be low and linked to tolerance problems.

Setting the scene.

Doctors have a critical role in ensuring good teamworking which improves patient outcomes. UK hospitals with more doctors in their boards have lower morbidity and better patient satisfaction. In the USA, hospitals with doctors as the CEO have better performance, but in the UK less than 5% of hospitals have doctors as the CEO. There is an urgent need to improve training in medical leadership among UK doctors and to make careers in medical management more attractive to high fliers. The Faculty of Medical Leadership and Management has launched standards of medical leadership and management which will give credibility to this field and ensure that highly qualified candidates are appointed to all levels of management posts within the NHS.

Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case-control study in patients with transient ischemic attacks.

BACKGROUND AND PURPOSE: The evidence that obstructive sleep apnea/hypopnea (OSAH) is a risk factor for ischemic cerebrovascular disease is inconclusive. We explored this relationship in transient ischemic attack (TIA) patients because they are less likely than stroke patients to have OSAH as a consequence of cerebrovascular disease. METHODS: We performed a case-control study among 86 patients with TIA from a hospital neurovascular clinic, matched for age (+/-5 years) and sex with controls from the referring local family practice registers. RESULTS: Forty-nine of the 86 matched pairs were male and the body mass index was similar among cases and controls. The primary outcome measure, the apnea/hypopnea index [AHI=number of (apneas+hypopneas)/h slept, measured during overnight polysomnography and scored blind to case-control status], was the same for cases and controls (21/hour). However, the median number of 4% desaturations during sleep was slightly greater in the cases (12/hour) than controls (6/hour, P=0.04). There were the expected associations between TIA and higher fibrinogen levels (TIA 3.3, control 3.0 g/L, P=0.01), previous myocardial infarction (TIA 22, control 6%, P=0.007), a history of ever smoking (TIA 71, control 54%, P=0.01), hypertension (TIA 51, control 21%, P=0.001), and raised cholesterol (TIA 27, control 10%, P=0.01), with a weak trend for diabetes mellitus (TIA 10, control 6%, P=0.4). CONCLUSIONS: OSAH does not appear to be strongly associated with TIAs.

Home diagnosis of the obstructive sleep apnoea/hypopnoea syndrome.

Polysomnography has been accepted by many as a "gold standard" for the diagnosis of the Obstructive Sleep Apnoea/Hypopnoea Syndrome (OSAHS). Although polysomnography is a good method for diagnosing OSAHS, there is no evidence that the results of polysomnography more accurately identify patients with the syndrome than more simple investigations which may be done at lower cost in the patient's home. This article examines the evidence for and against home sleep studies and concludes that home sleep studies have a role. Precisely what that role is will depend on financial and organisational aspects for each sleep centre.

Functional status in patients with narcolepsy.

OBJECTIVE: To describe health and functional status in treated narcolepsy patients and to compare it with normative data and with patients with another cause of sleepiness, the obstructive sleep apnea/hypopnea syndrome (OSAHS) patients. METHODS: A functional status survey in narcolepsy patients and in symptomatic untreated and CPAP treated OSAHS patients with an apnea-hypopnea index (AHI) >5 was assessed using the UK Short Form 36 (SF-36) questionnaire, the Functional Outcomes of Sleep Questionnaire (FOSQ) and the Epworth Sleepiness Scale (ESS). SF-36 scores in narcoleptics were compared to age and sex matched controls. Narcolepsy patients also replied to a psychosocial aspects questionnaire. Health history and demographic data were obtained via a review of medical records and postal survey. RESULTS: Forty-nine treated narcolepsy patients, 56 untreated OSAHS and 48 CPAP treated OSAHS patients attending the sleep disorders clinic were recruited for this study. Narcoleptics presented significantly lower scores in all SF-36 domains compared to normative data. No difference in SF-36 scores was found between narcoleptics and untreated OSAHS patients but narcoleptics were sleepier and had lower FOSQ scores. These treated narcolepsy patients had lower scores in two dimensions of the SF-36 and in all FOSQ domains compared to CPAP-treated OSAHS patients. CONCLUSIONS: Functional status in treated narcoleptics is poor.

Arterial stiffness and endothelial function in obstructive sleep apnoea/hypopnoea syndrome.

BACKGROUND: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is associated with increased cardiovascular morbidity and mortality. Our study examined arterial stiffness and endothelial function in subjects with OSAHS with no known cardiovascular disease compared to well-matched controls. METHODS: Twenty subjects with OSAHS (defined as apnoea-hypopnoea index [AHI] > or =15 and Epworth Sleepiness Scale score > or =11) without cardiovascular disease and 20 well-matched controls underwent a comprehensive evaluation of arterial stiffness and endothelial function. Arterial stiffness was measured by applanation tonometry and cardiovascular magnetic resonance imaging (MRI) and endothelial function assessed by measuring vascular reactivity after administration of glyceryl trinitrate and salbutamol. RESULTS: Subjects with OSAHS had increased arterial stiffness (augmentation index 19.3 [10.9] vs. 12.6 (10.2)%; p=0.017) and impaired endothelial function (change in augmentation index following salbutamol -4.3 (3.2) vs. -8.0 (4.9)%; p=0.02) compared to controls. Aortic distensibility, a measure of arterial stiffness, was negatively correlated with the AHI. CONCLUSIONS: Our findings suggest that even in the absence of known cardiovascular disease, subjects with OSAHS have increased arterial stiffness and impaired endothelial function and are at increased risk for cardiovascular disease.

The effect of continuous positive airway pressure therapy on arterial stiffness and endothelial function in obstructive sleep apnea: a randomized controlled trial in patients without cardiovascular disease.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality which may be mediated by increased arterial stiffness and endothelial dysfunction. Continuous positive airway pressure (CPAP) therapy improves excessive daytime somnolence (EDS), but its effect on vascular function in patients without preexisting cardiovascular disease (CVD) is unclear. METHODS: Fifty-three patients with OSA defined as an apnea-hypopnea index (AHI) of ⩾15 and without CVD were recruited into a double-blind, randomized, placebo-controlled, crossover trial of 12weeks of CPAP therapy, of whom 43 participants completed the study protocol. Arterial stiffness was assessed by measuring the augmentation index (AIx) and pulse wave velocity (PWV) by applanation tonometry and cardiovascular magnetic resonance imaging to determine aortic distensibility. Endothelial function was assessed by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. RESULTS: CPAP therapy lowered systolic blood pressure (SBP) (126mmHg [standard deviation {SD}, 12] vs 129mmHg [SD, 14]; P=.03), with a trend towards reduced AIx (15.5 [SD, 11.9] vs 16.6 [SD, 11.7]%; P=.08) but did not modify endothelial function. When subjects with (n=24) and without (n=19) EDS were separately examined, no effect of CPAP therapy on vascular function was seen. CONCLUSIONS: In patients without overt CVD, CPAP therapy had a nonsignificant effect on AIx and did not modify endothelial function.