The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

Disparities in self-reported healthcare access for airways disease in British Columbia, Canada, during the COVID-19 pandemic. Insights from a survey co-developed with people living with asthma and chronic obstructive pulmonary disease.

Patients' perspectives on the impact of the COVID-19 pandemic on their access to asthma and COPD healthcare could inform better, more equitable care delivery. We demonstrate this topic using British Columbia (BC), Canada, where the impact of the pandemic has not been described. We co-designed a cross-sectional survey with patient partners and administered it to a convenience sample of people living with asthma and COPD in BC between September 2020 and March 2021. We aimed to understand how access to healthcare for these conditions was affected during the pandemic. The survey asked respondents to report their characteristics, access to healthcare for asthma and COPD, types of services they found disrupted and telehealth (telephone or video appointment) use during the pandemic. We analysed 433 responses and found that access to healthcare for asthma and COPD was lower during the pandemic than pre-pandemic (p < 0.001). Specialty care services were most frequently reported as disrupted, while primary care, home care and diagnostics were least disrupted. Multivariable logistic regression revealed that access during the pandemic was positively associated with self-assessed financial ability (OR = 22.0, 95% CI: 7.0 - 84.0, p < 0.001, reference is disagreeing with having financial ability) and living in medium-sized urban areas (OR = 2.3, 95% CI: 1.0 - 5.2, p = 0.04, reference is rural areas). These disparities in access should be validated post-pandemic to confirm whether they still persist. They also indicate the continued relevance of exploring approaches for more equitable healthcare.

Obstructive Sleep Apnea Severity and the Risk of Occupational Injury: A Prospective Observational Cohort.

OBJECTIVE: To determine whether patients with obstructive sleep apnea (OSA) are at increased risk of occupational injury (OI) METHODS: Working patients (aged 18 to 65 who reported more than 10 h of work per week) who were referred to the University of British Columbia Sleep Laboratory for suspected OSA for polysomnogram (PSG) were recruited from 2003 to 2011. Patients completed an extensive survey the night of their PSG. Validated OI was obtained by linking patient data to Workers Compensation Board Claims Data. RESULTS: 1109 workers were studied; mean age was 47.1 years, median AHI was 15.0/h, median BMI was 30 kg/m2, 70.2% were male and 29% of patients worked in physical or manual related occupations. 78 patients (7.03%) suffered 140 OI in the 5 years after PSG. In a multivariate logistic regression model, OSA severity [defined as a log(AHI + 1)] was a significant predictor of OI (p = 0.04) after controlling for age, sex, BMI, and physical or manual related occupations. Patients with moderate and severe OSA had approximately two times the odds of an OI compared to patients without OSA (OR 1.99, 95% CI 0.96-4.44 and 2.00, 95% CI 0.96-4.49 for moderate and severe OSA groups, respectively). CONCLUSIONS: In this prospective study, OSA severity was independently associated with an increased risk of OI.

C-Reactive Protein Levels and the Risk of Incident Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Obstructive sleep apnoea and frequency of occupational injury.

We sought to determine whether patients with obstructive sleep apnoea (OSA) are at increased risk of occupational injury (OI). Patients referred to the University of British Columbia Hospital Sleep Laboratory for suspected OSA (May 2003 to July 2011 were recruited and rates and types of validated OI (that caused at least 1 day of disability) in the 5 years prior to polysomnography were calculated. In a sample of 1236, patients with OSA were twice as likely (OR=1.93, 95% CI 1.06 to 3.50, p=0.03) to suffer at least one OI compared with patients without OSA. This association was attenuated (OR=1.76, CI 0.86 to 3.59, p=0.12) after controlling for confounders. In a secondary analysis, patients with OSA were almost three times more likely (OR=2.88, CI 1.02 to 8.08, p=0.05) to suffer from an injury more likely related to reduced vigilance (eg, a fall or commercial motor vehicle crash) when compared with patients without OSA, and this again was attenuated after controlling for confounders (OR=2.42, CI 0.085 to 6.93, p=0.10).

New frontiers in obstructive sleep apnoea.

OSA (obstructive sleep apnoea), the most common respiratory disorder of sleep, is caused by the loss of upper airway dilating muscle activity during sleep superimposed on a narrow upper airway. This results in recurrent nocturnal asphyxia. Termination of these events usually requires arousal from sleep and results in sleep fragmentation and hypoxaemia, which leads to poor quality sleep, excessive daytime sleepiness, reduced quality of life and numerous other serious health consequences. Furthermore, patients with untreated sleep apnoea are at an increased risk of hypertension, stroke, heart failure and atrial fibrillation. Although there are many predisposing risk factors for OSA, including male gender, endocrine disorders, use of muscle relaxants, smoking, fluid retention and increased age, the strongest risk factor is obesity. The aim of the present review is to focus on three cutting-edge topics with respect to OSA. The section on animal models covers various strategies used to simulate the physiology or the effects of OSA in animals, and how these have helped to understand some of the underlying mechanisms of OSA. The section on diabetes discusses current evidence in both humans and animal models demonstrating that intermittent hypoxia and sleep fragmentation has a negative impact on glucose tolerance. Finally, the section on cardiovascular biomarkers reviews the evidence supporting the use of these biomarkers to both measure some of the negative consequences of OSA, as well as the potential benefits of OSA therapies.

Factors associated with disclosure of HIV status among a cohort of individuals on antiretroviral therapy in British Columbia, Canada.

We sought to examine the prevalence and correlates of HIV-disclosure among treatment-experienced individuals in British Columbia, Canada. Study participants completed an interviewer-administered survey between July 2007 and January 2010. The primary outcome of interest was disclosing one's HIV-positive status to all new sexual partners within the last 6 months. An exploratory logistic regression model was developed to identify variables independently associated with disclosure. Of the 657 participants included in this analysis, 73.4 % disclosed their HIV-positive status to all of their sexual partners. Factors independently associated with non-disclosure included identifying as a woman (adjusted odds ratio [AOR] 1.92; 95 % confidence interval [95 % CI] 1.13-3.27) or as a gay or bisexual man (AOR 2.45; 95 % CI 1.47-4.10). Behaviours that were independently associated with non-disclosure were having sex with a stranger (AOR 2.74; 95 % CI 1.46-5.17), not being on treatment at the time of interview (AOR 2.67; 95 % CI 1.40-5.11), and not always using a condom (AOR 1.78; 95 % CI 1.09-2.90). Future preventative strategies should focus on environmental and social factors that may inhibit vulnerable HIV-positive populations, such as women and gay or bisexual men, from safely disclosing their positive status.

Obstructive sleep apnea severity, circulating biomarkers, and cancer risk.

STUDY OBJECTIVES: To determine whether obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort. METHODS: Consenting adult patients at the University of British Columbia Hospital between 2003 and 2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram. Blood samples were collected the morning after polysomnography and processed for biomarkers of inflammation and angiogenesis. The clinical, polysomnography, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression was used to assess the association between OSA severity and biomarker concentrations with cancer risk. RESULTS: A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after polysomnography. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio = 1.08 per 10 events/h apnea-hypopnea index increase, confidence interval = 1.02-1.15, P = .015). In an exploratory analysis, 2 biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (hazard ratio per interquartile range pg/mL increase of endostatin = 1.45, confidence interval = 1.12-1.87, P = .01 and hazard ratio for interquartile range pg/mL increase of vascular cell adhesion molecule-1 = 1.48, confidence interval = 1.04-2.11, P = .03, respectively). CONCLUSIONS: OSA severity was an independent risk factor for cancer. Furthermore, 2 circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate patients with OSA with respect to cancer risk. CITATION: Hirsch Allen AJ, Kendzerska T, Bhatti P, et al. Obstructive sleep apnea severity, circulating biomarkers, and cancer risk. J Clin Sleep Med. 2024;20(9):1415-1422.

Association between sleep microarchitecture and cognition in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) increases the risk of cognitive impairment. Measures of sleep microarchitecture from EEG may help identify patients at risk of this complication. METHODS: Participants with suspected OSA (n=1142) underwent in-laboratory polysomnography and completed sleep and medical history questionnaires, and tests of global cognition (Montreal Cognitive Assessment, MoCA), memory (Rey Auditory Verbal Learning Test, RAVLT) and information processing speed (Digit-Symbol Coding, DSC). Associations between cognitive scores and stage 2 NREM sleep spindle density, power, frequency and %-fast (12-16Hz), odds-ratio product (ORP), normalized EEG power (EEGNP) and the delta:alpha ratio were assessed using multivariable linear regression (MLR) adjusted for age, sex, education, and total sleep time. Mediation analyses were performed to determine if sleep microarchitecture indices mediate the negative effect of OSA on cognition. RESULTS: All spindle characteristics were lower in participants with moderate and severe OSA (p≤0.001, versus no/mild OSA) and positively associated with MoCA, RAVLT and DSC scores (false discovery rate corrected p-value, q≤0.026), except spindle power which was not associated with RAVLT (q=0.185). ORP during NREM sleep (ORPNREM) was highest in severe OSA participants (p≤0.001) but neither ORPNREM (q≥0.230) nor the delta:alpha ratio were associated with cognitive scores in MLR analyses (q≥0.166). In mediation analyses, spindle density and EEGNP (p≥0.048) mediated moderate-to-severe OSA's negative effect on MoCA scores while ORPNREM, spindle power and %-fast spindles mediated OSA's negative effect on DSC scores (p≤0.018). CONCLUSION: Altered spindle activity, ORP and normalized EEG power may be important contributors to cognitive deficits in patients with OSA.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

Online health information seeking among Jewish and Arab adolescents in Israel: results from a national school survey.

This study examined patterns and determinants of seeking online health information among a nationally representative sample of 7,028 Jewish and Arab 7th- through 12th-grade students in 158 schools in Israel. Nearly all respondents (98.7%) reported Internet access, and 52.1% reported having sought online health information in the past year. Arab students (63%) were more likely than Jewish students (48%) to seek online health information. Population-group and sex differences in health topics sought online were identified, although fitness/exercise was most common across groups. Multivariate regression models revealed that having sought health information from other sources was the strongest independent correlate of online health information-seeking among Jews (adjusted odds ratio = 8.93, 95% CI [7.70, 10.36]) and Arabs (adjusted odds ratio = 9.77, 95% CI [7.27, 13.13]). Other factors associated with seeking online health information common to both groups were level of trust in online health information, Internet skill level, having discussed health/medical issues with a health care provider in the past year, and school performance. The most common reasons for not seeking online health information were a preference to receive information from a health professional and lack of interest in health/medical issues. The closing of the digital divide between Jews and Arabs represents a move toward equality. Identifying and addressing factors underpinning online health information-seeking behaviors is essential to improve the health status of Israeli youth and reduce health disparities.

Association of insomnia and short sleep duration, alone or with comorbid obstructive sleep apnea, and the risk of chronic kidney disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA), sleep fragmentation, and short sleep duration (SD) have been associated with chronic kidney disease (CKD). However, these potential mechanisms for CKD have not been compared in the same cohort. This study investigated the independent and combined impact of OSA and insomnia with short sleep duration on the risk of CKD progression in a sleep clinic population. METHODS: In a cross-sectional study design, adults with suspected OSA completed an overnight sleep study and a questionnaire that included the Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). They also provided blood and urine samples for measurement of the glomerular filtration rate and urine albumin:creatinine ratio, from which the risk of CKD progression was determined. RESULTS: Participants (n = 732, 41% female, 55 ± 13 years) were categorized into four groups: no/mild OSA without insomnia (NM-OSA, n = 203), insomnia with SD without OSA (Insomnia-SD, n = 104), moderate-to-severe OSA without insomnia (MS-OSA, n = 242), and comorbid insomnia and OSA with SD (COMISA-SD, n = 183). After stratification, 12.8% of NM-OSA, 15.4% of Insomnia-SD, 28.9% of MS-OSA, and 31.7% of the COMISA-SD participants had an increased risk of CKD progression. Compared to NM-OSA, the odds ratio (OR) for an increased risk of CKD progression was not increased in Insomnia-SD (OR 0.95, confidence interval [CI]: 0.45-1.99) and was increased to the same degree in MS-OSA (OR 2.79, CI: 1.60-4.85) and COMISA-SD (OR 3.04, CI: 1.69-5.47). However, the ORs were similar between the MS-OSA and COMISA-SD groups across all statistical models (p ≥ .883). CONCLUSIONS: In a sleep clinic population, insomnia with short sleep duration does not increase the risk of CKD progression; nor does it further increase the risk of CKD progression associated with moderate-to-severe OSA.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. METHODS: Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. RESULTS: 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. CONCLUSION: Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD. RESEARCH QUESTION: Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA? STUDY DESIGN AND METHODS: Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases. RESULTS: 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40-9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16-8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94-11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19-2.38), p-value for interaction = 0.07. INTERPRETATION: In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

Cognitive Function in a Sleep Clinic Cohort of Patients with Obstructive Sleep Apnea.

Rationale: Obstructive sleep apnea (OSA) is associated with an increased risk of mild cognitive impairment (MCI) within the general population. However, MCI risk in sleep-clinic populations of patients with OSA is poorly characterized.Objectives: To determine the prevalence of MCI in a sleep-clinic population of patients with OSA and which patients are at the greatest risk for this complication.Methods: Adults (n = 1,084) referred to three academic sleep centers for suspected OSA who had home sleep apnea testing or in-laboratory polysomnography were recruited. Patients completed sleep and medical history questionnaires, the Montreal Cognitive Assessment Test (MoCA) of global cognition, the Rey Auditory Verbal Learning Test of memory, and the Wechsler Adult Intelligence Scale-Fourth Edition Digit-Symbol Coding (DSC) subtest of information processing speed.Results: A MoCA score <26 (range 0-30) was operationally defined as MCI. MCI was present in 47.9% of our entire patient cohort, increasing to >55.3% in patients with moderate and severe OSA. Patients with a MoCA <26 were predominantly older males with more severe OSA, hypoxemia, and vascular comorbidities. Moderate and severe OSA were independently associated with >70% higher odds for MCI compared with patients with no OSA (P = 0.003). Memory and information processing speed was lower than age-matched normal values (P < 0.001), with lower MoCA and DSC scores associated with a higher oxygen desaturation index and nocturnal hypoxemia.Conclusions: Cognitive impairment is highly prevalent in patients referred to sleep clinics for suspected OSA, occurring predominantly in older males with moderate to severe OSA and concurrent vascular comorbidities. Moderate to severe OSA is an independent risk factor for MCI.

Influence of residency training on multiple attempts at endotracheal intubation.

PURPOSE: Endotracheal intubation (ETI) of critically ill patients is a high-risk procedure that is commonly performed by resident physicians. Multiple attempts (>/=2) at intubation have previously been shown to be associated with severe complications. Our goal was to determine the association between year of training, type of residency, and multiple attempts at ETI. METHODS: This was a cohort study of 191 critically ill patients requiring urgent intubation at two tertiary care teaching hospitals in Vancouver, Canada. Multivariable logistic regression was used to model the association between postgraduate year (PGY) of training and multiple attempts at ETI. RESULTS: The majority of ETIs were performed for respiratory failure (68.6%) from the hours of 07:00-19:00 (60.7%). Expert supervision was present for 78.5% of the intubations. Multiple attempts at ETI were required in 62%, 48%, and 34% of patients whose initial attempt was performed by PGY-1, PGY-2, and PGY-3 non-anesthesiology residents, respectively. Anesthesiology residents required multiple attempts at ETI in 15% of patients, regardless of the year of training. The multivariable model showed that both higher year of training (risk ratio [RR] 0.74; 95% confidence interval [CI] 0.54-0.93; P < 0.01) and residency training in anesthesiology (RR 0.52; 95% CI 0.20-1.0; P = 0.05) were independently associated with a decreased risk of multiple intubation attempts. Finally, intubations performed at night were associated with an increased risk of multiple intubation attempts (RR 1.3; 95% CI 1.0-1.4; P = 0.03). CONCLUSION: Year of training, type of residency, and time of day were significantly associated with multiple tracheal intubation attempts in the critical care setting.

Circulating biomarkers to identify cardiometabolic complications in patients with Obstructive Sleep Apnea: A systematic review.

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.

Adhesion molecule gene variants and plasma protein levels in patients with suspected obstructive sleep apnea.

STUDY OBJECTIVES: Untreated 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. METHODS: We measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms. RESULTS: The 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). CONCLUSIONS: These 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.

The effect of OSA on work disability and work-related injuries.

OSA is a common yet underdiagnosed respiratory disorder characterized by recurrent upper airway obstruction during sleep. OSA results in sleep fragmentation and repetitive hypoxemia and is associated with a variety of adverse consequences including excessive daytime sleepiness, reduced quality of life, cardiovascular disease, decreased learning skills, and neurocognitive impairment. Neurocognitive impairments that have been linked to poor sleep include memory deficits, decreased learning skills, inability to concentrate, and decreased alertness. Furthermore, the societal and economic costs of OSA are substantial; for example, patients with OSA have a significantly greater risk of motor vehicle crashes, consume more health-care resources, and have associated annual costs in the billions of dollars per year. It is increasingly recognized that OSA may also have substantial economic consequences. Specifically, there is accumulating evidence implicating OSA as an important contributor to work disability (including absenteeism, presenteeism) and work-related injuries. This review summarizes the current state of knowledge in these two areas.