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To investigate the relationship between obstructive sleep apnea (OSA) severity, body mass index (BMI), and circulating levels of inflammatory adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). A cross-sectional clinical cohort study on all consecutive adults referred to the University of British Columbia (UBC) Sleep Laboratory for a polysomnogram (PSG) for suspected OSA provided a morning blood sample. Samples were analyzed with multiplex immune assay (MilliporeSigma, CA) to assess the levels of adhesion molecules. 488 patients were studied; the majority were male (68%) with a mean age of 50 yrs, mean AHI of 23 events/hour, and mean BMI of 32 kg/m2. In multivariable linear regression models, all three adhesion molecules were significantly associated with BMI (E-selectin p

Background Distinct symptom subtypes are found in patients with OSA. The association between these subtypes and neurocognitive function is unclear. Objective: The purposes of this study were to assess whether OSA symptom subtypes are present in a cohort of Canadian patients with suspected OSA and evaluate the relationship between subtypes and neurocognitive function. Methods Patients with suspected OSA who completed a symptom questionnaire and underwent testing for OSA were included. Symptom subtypes were identified using latent class analysis. Associations between subtypes and neurocognitive outcomes (Montreal Cognitive Assessment [MoCA], Rey Auditory Verbal Learning Test [RAVLT], Wechsler Adult Intelligence Scale [WAIS-IV], Digit-Symbol Coding subtest [DSC]) were assessed using analysis of covariance (ANCOVA), controlling for relevant covariates. Results Four symptom subtypes were identified in patients with OSA (oxygen desaturation index ≥5 events/hour). Three were similar to prior studies, including the Excessively Sleepy (N=405), Disturbed Sleep (N=382) and Minimally Symptomatic (N=280), and one was a novel subtype in our sample defined as Excessively Sleepy with Disturbed Sleep (N=247). After covariate adjustment, statistically significant differences among subtypes (p=0.037) and among subtypes and patients without OSA (p=0.044) were observed in DSC scores; the Minimally Symptomatic subtype had evidence of higher DSC scores than all other groups, including non-OSA patients. No differences were seen in MoCA or RAVLT. Conclusions Results support the existence of previously identified OSA symptom subtypes of excessively sleepy, disturbed sleep and minimally symptomatic in a clinical sample from Canada. Subtypes were not consistently associated with neurocognitive function across multiple instruments.

Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43–38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.

Background Air pollution and OSA are independently associated with systemic inflammation, but it is unknown if these exposures interact to influence systemic inflammation. Research Question The study objective was to determine the relative importance of these factors and their combined potential to influence systemic inflammation in patients under assessment for sleep ailments. Study Design and Methods A total of 315 patients contributed data, including a questionnaire, polysomnogram, and morning serum IL-6 and IL-10 concentrations. For each patient, residential annual average air pollution exposure (nitrogen dioxide [NO2], black carbon [BC], and particulate matter with an aerodynamic diameter ≤ 2.5 μm [PM2.5]) was estimated with a land use regression model. Linear regression modeling was used adjusting for age, sex, apnea-hypopnea index, BMI, smoking, socioeconomic status, and comorbidities. Results In adjusted models, quartile 4 PM2.5 exposure (compared with quartiles 1-3) was associated with increased IL-6 and IL-10 concentrations (estimated adjusted, 7.1 pg/mL [95% CI, 2.5-11.7; P Interpretation Long-term residential PM2.5 exposure was associated with increased IL-6 and IL-10 concentrations in patients evaluated for suspected OSA. BC exposure was also associated with increased IL-6 but only in the subgroup of patients with moderate to severe OSA. These data suggest the potential for joint effects of moderate to severe OSA and air pollution on systemic inflammation.

Study objectivesUntreated obstructive sleep apnea (OSA) patients have an increased risk of cardiovascular disease (CVD). Adhesion molecules, including soluble E-selectin (sE-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1), are associated with incident CVD. We hypothesized that specific genetic variants will be associated with plasma levels of adhesion molecules in suspected OSA patients. We also hypothesized that there may be an interaction between these variants and OSA.MethodsWe measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms.ResultsThe most significant association was between the ABO rs579459 polymorphism and sE-selectin levels (P = 7×10-21), with the major allele T associated with higher levels. The direction of effect and proportion of the variance in sE-selectin levels accounted for by rs579459 (16%) was consistent with estimates from non-OSA cohorts. In a multivariate regression analysis, addition of rs579459 improved the model performance in predicting sE-selectin levels. Three polymorphisms were nominally associated with sICAM-1 levels but none with sVCAM-1 levels. The combination of severe OSA and two rs579459 T alleles identified a group of patients with high sE-selectin levels; however, the increase in sE-selectin levels associated with severe OSA was greater in patients without two T alleles (P = 0.05 test for interaction).ConclusionsThese genetic polymorphisms may help to identify patients at greatest risk of incident CVD and may help in developing a more precision-based approach to OSA care.

Untreated Obstructive sleep apnea (OSA) is associated with an increased risk of cardiometabolic diseases such as diabetes and myocardial infarction. However, it is difficult to predict which patients are at particularly high risk. This systematic review aimed to identify potentially useful circulating biomarkers that could predict cardiometabolic complications in OSA. We searched Cochrane (EBM), EMBASE, Medline, PubMed, and Web of Science databases. Search concepts included: "Obstructive Sleep Apnea", "Biomarkers" and "Risk-Stratification". Manuscripts were included if they studied adults with OSA, circulating (blood) markers, and relationships with clinical outcomes. After screening, 10 were included. Studies addressed cardiovascular disease, type 2 diabetes, end-stage renal disease and metabolic syndrome. In general, levels of inflammatory markers, adhesion molecules, and vascular proteins were associated with the presence of cardiometabolic disease in OSA patients. Although studies regarding prognostic circulating biomarkers in OSA are limited, a number of potentially promising biomarkers were identified in our review. However, more research is needed using prospective cohorts to determine which biomarkers are most robustly associated with and useful in predicting future cardiovascular and metabolic sequelae in OSA patients. Identification of such biomarkers could guide more selective and targeted therapy for OSA in an emerging era of precision-based medicine.

The impact of obstructive sleep apnea (OSA) on the development of atherosclerotic cardiovascular disease (CVD) in the absence of overt CVD or risk factors is unclear. Our purpose was to assess whether patients with OSA without overt CVD or risk factors have subclinical atherosclerosis as evaluated by carotid intima medial thickness (CIMT) compared to matched controls. We measured CIMT in patients >40 years old, who underwent polysomnography for suspected OSA and did not have a history of CVD or risk factors (smoking, hypertension, diabetes, hyperlipidemia). OSA severity was classified according to apnea–hypopnea index. Serum levels of high-sensitivity C-reactive protein, fibrinogen, and lipids were assessed and relationships with OSA severity explored. CIMT measurements from patients with OSA were compared those of to age-, gender-, and BMI-matched controls from a community-based cohort without known CVD or OSA. Fifty-one patients were studied. Of these, patients with severe OSA had an increased CIMT compared to patients without OSA, but the relationship was not significant after controlling for age (p = 0.10). However, 37 patients had OSA and were matched to 105 controls. CIMT was significantly increased in OSA patients versus controls (0.77 vs. 0.68 mm, p = 0.03). The difference between patients and controls was greater for patients with severe OSA (0.83 vs. 0.71 mm) than for patients with mild-to-moderate OSA (0.71 vs. 0.67 mm). Patients with OSA but without a history of or risk factors for CVD have increased CIMT compared to a BMI-, age-, and gender-matched cohort. This provides evidence that OSA is an independent risk factor for the development of CVD.

STUDY OBJECTIVES First-line therapy for patients with moderate to severe obstructive sleep apnea (OSA) is positive airway pressure (PAP). Although PAP is a highly efficacious treatment, adherence to PAP is still a substantial clinical problem. The objective of this study was to determine whether PAP adherence can be improved with a telemedicine monitoring system. DESIGN A nonblinded, single-center, randomized controlled trial that compared standard PAP treatment versus PAP treatment and a telemedicine monitoring system SETTING University sleep disorders program in British Columbia, Canada PATIENTS Adult patients (≥ 19 yr of age) with moderate to severe OSA (apnea hypopnea index (AHI) ≥ 15 events/hr determined by polysomnography) prescribed PAP INTERVENTIONS: Patients were randomized to either standard care with an autotitrating PAP machine or an autotitrating PAP machine that transmitted physiologic information (i.e., adherence, air leak, residual AHI) daily to a website that could be reviewed. If problems were identified from information from the website, the patient was contacted by telephone as necessary. MEASUREMENTS PAP adherence after 3 mo, subjective sleep quality, and side effects RESULTS Seventy-five patients were enrolled; 39 were randomized to telemedicine and 36 to standard care. The mean age ± standard deviation (SD) was 53.5 ± 11.2 yr, mean AHI was 41.6 ± 22.1 events/hr, and 80% of patients were male. After 3 mo, mean PAP adherence was significantly greater in the telemedicine arm (191 min per day) versus the standard arm (105 min per day; mean difference = 87 min, 95% confidence interval (CI): 25-148 min, P = 0.006, unpaired t test). On days when PAP was used, mean adherence was 321 min in the telemedicine arm and 207 min in the standard arm (difference = 113 min, 95% CI: 62-164 min, P < 0.0001). Significant independent predictors of adherence included age, baseline Epworth Sleepiness Scale score, and use of telemedicine. On average, an additional 67 min of technician time was spent on patients in the telemedicine arm compared with the standard arm (P = 0.0001). CONCLUSIONS PAP adherence can be improved with the use of a web-based telemedicine system at the initiation of treatment.

Polysomnography (PSG), despite limited availability and high cost, is currently recommended for diagnosis of obstructive sleep apnea and titration of effective continuous positive airway pressure (CPAP).To test the utility of a diagnostic algorithm in conjunction with ambulatory CPAP titration in initial management of obstructive sleep apnea.A randomized, controlled, open-label trial that compared standard PSG with ambulatory CPAP titration in high-risk patients identified by a diagnostic algorithm.A tertiary referral sleep disorders program in Vancouver, British Columbia, Canada.68 patients with a high pretest probability of moderate to severe obstructive sleep apnea (apnea-hypopnea index [AHI]15 episodes/h) identified by sequential application of the Epworth Sleepiness Scale (ESS) score, Sleep Apnea Clinical Score, and overnight oximetry.Patients were randomly assigned to PSG or ambulatory titration by using a combination of auto-CPAP and overnight oximetry. They were observed for 3 months.Apnea-hypopnea index on CPAP, ESS score, quality of life, and CPAP adherence.The PSG and ambulatory groups had similar median BMI (38 kg/m2), age (55 years), ESS score (14 points), and respiratory disturbance index (31 episodes of respiratory disturbance/h). Each episode is determined by a computer algorithm based on analysis of oxygen saturation measured by pulse oximetry. After 3 months, there were no differences in the primary outcome, AHI on CPAP (median, 3.2 vs. 2.5; difference, 0.8/h [95% CI, -0.9 to 2.3]) (P = 0.31), between the PSG and ambulatory groups, or in the secondary outcomes, ESS score, Sleep Apnea Quality of Life Index, and CPAP. Adherence to CPAP therapy was better in the ambulatory group than in the PSG group (median, 5.4 vs. 6.0; difference, -1.12 h/night [CI, -2.0 to 0.2]) (P = 0.021).In the initial management of patients with a high probability of obstructive sleep apnea, PSG confers no advantage over the ambulatory approach in terms of diagnosis and CPAP titration. The ambulatory approach may improve adherence to treatment. When access to PSG is inadequate, the ambulatory approach can be used to expedite management of patients most in need of treatment.