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

STUDY OBJECTIVES: To determine if 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 2003-2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram (PSG). Blood samples were collected the morning after PSG and processed for biomarkers of inflammation and angiogenesis. The clinical, PSG, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression were 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 PSG. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio (HR) = 1.08 per 10 events/h apnea-hypopnea index (AHI) increase, CI = 1.02-1.15, p=0.015). In an exploratory analysis, two biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (HR per interquartile range (IQR) pg/mL increase of endostatin = 1.45, CI = 1.12-1.87, p=0.01 and HR for IQR pg/mL increase of VCAM-1 = 1.48, CI = 1.04-2.11, p=0.03, respectively). CONCLUSIONS: OSA severity was an independent risk factor for cancer. Furthermore, two 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 OSA patients with respect to cancer risk.

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.

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.

Circulating markers of oxidative stress and risk of incident cardiovascular events in obstructive sleep apnea.

The identification of which patients with obstructive sleep apnea (OSA) are more likely to develop cardiovascular disease (CVD) remains a challenge. OSA causes oxidative stress (OS) which may contribute to CVD pathogenesis. Therefore, OS markers could be useful in risk-stratifying cardiovascular (CV) risk in OSA patients. The purpose of this pilot study was to assess whether three OS marker levels could be associated with incident CVD in suspected OSA patients. Morning plasma levels of 8-isoprostane, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and superoxide dismutase (SOD) were measured in patients with suspected OSA referred for a polysomnogram (PSG). A composite outcome of CV events was defined by linkage with provincial administrative health databases. Cox proportional hazards models were used to assess the relationship between the levels of OS markers and events. 352 patients were included (mean age of 51.4 years, 68% male, median apnea hypopnea index of 16/h). Thirty-one first CV events occurred over an 8-year follow-up. In univariate or fully adjusted models, none of the OS markers were significantly associated with incident CV events (hazard ratio in adjusted models of: 1.25 (95% CI 0.56-2.80, p = 0.59), 1.15 (0.52-2.57, p = 0.73), 0.77 (0.37-1.61, p = 0.48), for 8-OHdG, 8-isoprostane and SOD; however, confidence intervals were wide. In this small preliminary study, oxidative stress markers were not significantly associated with risk of CV events. However, moderate associations between these markers and risk of CV events are possible and should be the focus of future larger studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00399-0.

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.

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.

Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study.

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.