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.

Perioperative myocardial injury risk after elective knee and hip arthroplasty in patients with a high risk of obstructive sleep apnea.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) occurs in approximately 8-13% of patients and has significant 30-day mortality. Patients with obstructive sleep apnea (OSA) suffer recurrent hypoxemia during sleep and surgical patients with OSA are known to have increased risk of cardiorespiratory complications. We hypothesized that patients at high risk for OSA may have an increased risk of MINS. As a secondary analysis, we assessed rates of postoperative cardiopulmonary complications. METHODS: Adult patients undergoing elective knee or hip arthroplasty with STOPBANG score ≥ 5 were recruited. MINS was determined by measuring troponin-I on postoperative days 1 and 2. RESULTS: A total of 82 patients were studied. Only one patient had a positive troponin (MINS rate of 1.2%). The rate of cardiopulmonary complications was low (4.9%) and the 30-day mortality rate for these patients was 0. CONCLUSION: The incidence of MINS and postoperative cardiopulmonary complications in patients with elective arthroplasty and a high risk of OSA were low.

Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

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.

Obstructive Sleep Apnea Severity, Body Mass Index, and Circulating Levels of Cellular Adhesion Molecules.

PURPOSE: 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). METHODS: 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. RESULTS: 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 < 0.0001; ICAM-1 p = 0.0007; VCAM-1 p = 0.0003). However, only E-selectin was independently associated with AHI (p = 0.02); there was no significant interaction between AHI and BMI for E-selectin (p = 0.33). CONCLUSIONS: Although all three adhesion molecules were associated with BMI, only E-selectin was independently associated with OSA severity. Future studies are needed to determine the clinical significance of the relationship between E-selectin and OSA.

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 alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review.

STUDY OBJECTIVES: Polysomnograms (PSGs) collect a plethora of physiologic signals across the night. However, few of these PSG data are incorporated into standard reports, and hence, ultimately, under-utilized in clinical decision making. Recently, there has been substantial interest regarding novel alternative PSG metrics that may help to predict obstructive sleep apnea (OSA)-related outcomes better than standard PSG metrics such as the apnea-hypopnea index. We systematically review the recent literature for studies that examined the use of alternative PSG metrics in the context of OSA and their association with health outcomes. METHODS: We systematically searched EMBASE, MEDLINE, and the Cochrane Database of Systematic Reviews for studies published between 2000 and 2022 for those that reported alternative metrics derived from PSG in adults and related them to OSA-related outcomes. RESULTS: Of the 186 initial studies identified by the original search, data from 31 studies were ultimately included in the final analysis. Numerous metrics were identified that were significantly related to a broad range of outcomes. We categorized the outcomes into 2 main subgroups: (1) cardiovascular/metabolic outcomes and mortality and (2) cognitive function- and vigilance-related outcomes. Four general categories of alternative metrics were identified based on signals analyzed: autonomic/hemodynamic metrics, electroencephalographic metrics, oximetric metrics, and respiratory event-related metrics. CONCLUSIONS: We have summarized the current landscape of literature for alternative PSG metrics relating to risk prediction in OSA. Although promising, further prospective observational studies are needed to verify findings from other cohorts, and to assess the clinical utility of these metrics. CITATION: Hajipour M, Baumann B, Azarbarzin A, et al. Association of alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review. J Clin Sleep Med. 2023;19(2):225-242.

Diagnosing ventilator-associated pneumonia (VAP) in UK NHS ICUs: the perceived value and role of a novel optical technology.

BACKGROUND: Diagnosing ventilator-associated pneumonia (VAP) in an intensive care unit (ICU) is a complex process. Our aim was to collect, evaluate and represent the information relating to current clinical practice for the diagnosis of VAP in UK NHS ICUs, and to explore the potential value and role of a novel diagnostic for VAP, which uses optical molecular alveoscopy to visualise the alveolar space. METHODS: Qualitative study performing semi-structured interviews with clinical experts. Interviews were recorded, transcribed, and thematically analysed. A flow diagram of the VAP patient pathway was elicited and validated with the expert interviewees. Fourteen clinicians were interviewed from a range of UK NHS hospitals: 12 ICU consultants, 1 professor of respiratory medicine and 1 professor of critical care. RESULTS: Five themes were identified, relating to [1] current practice for the diagnosis of VAP, [2] current clinical need in VAP diagnostics, [3] the potential value and role of the technology, [4] the barriers to adoption and [5] the evidence requirements for the technology, to help facilitate a successful adoption. These themes indicated that diagnosis of VAP is extremely difficult, as is the decision to stop antibiotic treatment. The analysis revealed that there is a clinical need for a diagnostic that provides an accurate and timely diagnosis of the causative pathogen, without the long delays associated with return of culture results, and which is not dangerous to the patient. It was determined that the technology would satisfy important aspects of this clinical need for diagnosing VAP (and pneumonia, more generally), but would require further evidence on safety and efficacy in the patient population to facilitate adoption. CONCLUSIONS: Care pathway analysis performed in this study was deemed accurate and representative of current practice for diagnosing VAP in a UK ICU as determined by relevant clinical experts, and explored the value and role of a novel diagnostic, which uses optical technology, and could streamline the diagnostic pathway for VAP and other pneumonias.

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.

Symptom subtypes and risk of incident cardiovascular and cerebrovascular disease in a clinic-based obstructive sleep apnea cohort.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease, but predicting those at greatest risk is challenging. Using latent class analysis, patients with OSA can be placed into discrete symptom subtypes. The aim of this study was to determine whether symptom subtypes are associated with future cerebrovascular disease in patients with OSA in a clinic-based cohort. METHODS: Patients with suspected OSA referred for a polysomnogram at an academic sleep center completed a comprehensive symptom survey. Patients with OSA (apnea-hypopnea index ≥ 5 events/h) were then placed into symptom subtypes based on responses to survey questions using latent class analysis. Cardiovascular events (stroke, myocardial infarction, unstable angina, bypass grafting, percutaneous coronary intervention, cardiac resynchronization therapy, defibrillation) occurring within 8 years of polysomnogram were identified by linkage to provincial health databases. RESULTS: 1,607 patients were studied, of whom 1,292 had OSA. One hundred forty first events occurred within 8 years of polysomnogram. Patients in the excessively sleepy with disturbed sleep subtype had a significantly increased rate of events compared to the minimally symptomatic subtype (hazard ratio = 2.25, 95% confidence interval: 1.02-4.94; P = .04). Two symptoms (restless legs and dozing off or sleeping while talking to someone) were significantly associated with future risk of cerebrovascular disease (hazard ratio = 1.68, 1.12-2.49 and 4.23, 1.61-11.16, respectively). CONCLUSIONS: Patients with OSA in the clinic who are in the excessively sleepy with disturbed sleep subtype are significantly more likely to have a future cardiovascular event. This underscores the importance of understanding clinical heterogeneity and incorporating symptom subtype definitions into routine clinical care. CITATION: Allen AJH, Jen R, Mazzotti DR, et al. Symptom subtypes and risk of incident cardiovascular and cerebrovascular disease in a clinic-based obstructive sleep apnea cohort. J Clin Sleep Med. 2022;18(9):2093-2102.