Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation.

BACKGROUND: In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-ß signalling, which promotes cell cancer progression through epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed. METHODS: In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-ß were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions. RESULTS: PSPC1 levels were higher in patients with moderate-severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-ß expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics. CONCLUSION: In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.

Proangiogenic factor midkine is increased in melanoma patients with sleep apnea and induces tumor cell proliferation.

Midkine (MDK) might mediate the proangiogenic effect of intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) and cutaneous melanoma (CM). We compare circulating MDK in CM patients with and without OSA, and their relationship with tumor aggressiveness, while exploring in vitro effects of soluble MDK on human lymphatic endothelial (HLEC) and melanoma cell proliferation. In 360 CM patients, sleep studies and MDK serum level measurements were performed. The effect of MDK on cell proliferation was assessed using HLEC and melanoma cell lines with patient sera under both normoxia and IH. MDK levels were higher in severe OSA compared to mild OSA or non-OSA patients, whereas no differences in VEGF levels emerged. In OSA patients, MDK levels correlated with nocturnal hypoxemia and CM mitotic rate. In vitro, MDK promotes HLEC proliferation under IH conditions. Moreover, cultures of the human melanoma cell line C81-61 with sera from patients with the highest MDK levels promoted tumor cell proliferation, which was attenuated after the addition of MDK antibody. These responses were enhanced by IH exposures. In conclusion, in CM patients, OSA severity is associated with higher MDK levels, which, appear to enhance both the lymphangiogenesis as the intrinsic aggressiveness of CM tumor cells.

Interleukin 6 as a marker of depression in women with sleep apnea.

Depression is common in women with obstructive sleep apnea (OSA), but objective markers of depression have not yet been explored in such patients. We hypothesized that inflammation and antioxidant biomarkers may be associated with depression in a cohort of OSA women. We conducted a multicentre, cross-sectional study in 247 women diagnosed with moderate-to-severe OSA. Depression was assessed by the depression subscale of the Hospital Anxiety and Depression Questionnaire (HAD-D) and defined as a score ≥11. Associations between tumour necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF) plasma levels and depression were assessed. The women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index (BMI) of 33.5 (29.0-38.3) Kg/m2 , Epworth Sleepiness Scale (ESS) score of 10 (6-13) and apnea-hypopnea index (AHI) of 33.3 (22.8-49.3). Logistic regression analyses revealed that only IL6 levels were associated with the presence of depression (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.34), whereas linear regression further confirmed that IL6 levels were significantly associated with HAD-D scores (ß = .154; 95% CI, 0.03-0.30). Multivariate regression analysis showed that IL6 (OR, 1.22; 95% CI, 1.09-1.36), ESS (OR, 1.10; 95% CI 1.02-1.19) and physical activity <30 min/day (OR, 2.51; 95% CI, 1.25-5.05) were independent predictors of depression. Thus, we conclude that in a cohort of women with moderate-to-severe OSA, IL6 levels are independently associated with the presence of depression and correlate with depression scores. Low physical activity and higher ESS scores are also independent indicators of risk of depression in this population.

Obstructive Sleep Apnea and Arterial Hypertension: Implications of Treatment Adherence.

PURPOSE OF REVIEW: This review seeks to present an overview of the recent literature on the importance of CPAP and antihypertensive treatment adherence in blood pressure control of hypertensive patients, especially those with obstructive sleep apnea. RECENT FINDINGS: Although it is unquestionable that a good adherence to CPAP and antihypertensive drugs is crucial to improvements in sleep-related symptoms, blood pressure levels (even the modest reductions of 2-2.5 mmHg achieved by CPAP treatment) and future cardiovascular risk, this adherence decreases over time, despite efforts made toward behavioral intervention and monitoring. Curiously, although taking a drug would seem to be easier than the use of CPAP treatment, based on current information, it seems that the compliance with drug treatment in hypertensive subjects is not better than that achieved with CPAP treatment in OSA patients with hypertension. However, some studies have shown some phenotypes of hypertensive and OSA patients with good adherence and better hypertensive effect, such as those with uncontrolled blood pressure (resistant and refractory hypertension), severe forms of sleep apnea, and more sleep-related symptoms, especially a higher degree of diurnal hypersomnia. The positive effect of antihypertensive drugs and CPAP treatment on blood pressure levels depends on the degree of treatment adherence, especially in forms of uncontrolled hypertension, but this adherence decreases over time. Educational programs and new devices are needed to improve adherence to treatment in these patients, along with fuller understanding of the different patterns and phenotypes of non-adherence.

Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?

Obstructive sleep apnoea (OSA) is a prevalent disorder associated with increased cardiovascular, metabolic and neurocognitive morbidity. Recently, an increasing number of basic, clinical and epidemiological reports have suggested that OSA may also increase the risk of cancer, and adversely impact cancer progression and outcomes. This hypothesis is convincingly supported by biological evidence linking certain solid tumours and hypoxia, as well as by experimental studies involving cell and animal models testing the effects of intermittent hypoxia and sleep fragmentation that characterize OSA. However, the clinical and epidemiological studies do not conclusively confirm that OSA adversely affects cancer, even if they hold true for specific cancers such as melanoma. It is likely that the inconclusive studies reflect that they were not specifically designed to test the hypothesis or because of the heterogeneity of the relationship of OSA with different cancer types or even sub-types. This review critically focusses on the extant basic, clinical, and epidemiological evidence while formulating proposed directions on how the field may move forward.

Increased Incidence of Stroke, but Not Coronary Heart Disease, in Elderly Patients With Sleep Apnea.

Background and Purpose- The influence of age on the relationship between obstructive sleep apnea (OSA) and the incidence of hard cardiovascular events remains controversial. We sought to analyze the relationship between OSA and the incidence of stroke and coronary heart disease in a large cohort of elderly patients, as well as to investigate the role of continuous positive airway pressure (CPAP) treatment in these associations. Methods- Post hoc analysis of a prospective observational study of consecutive patients ≥65 years studied for OSA suspicion at 2 Spanish University Hospitals. Patients with an apnea-hypopnea index (AHI) <15 were the reference group. OSA was defined by an AHI ≥15 and classified as untreated (CPAP not prescribed or compliance <4 hours/day), mild-moderate (AHI 15-29), untreated severe (AHI ≥30), and CPAP-treated (AHI ≥15 and CPAP compliance ≥4 hours/day). Results- 859 and 794 elderly patients were included in the stroke and coronary heart disease analyses, respectively. The median (interquartile range) follow-up was 72 (50-88.5) and 71 (51.5-89) months, respectively. Compared with the reference group, the fully adjusted hazard ratios for the incidence of stroke were 3.42 (95% CI, 1.37-8.52), 1.02 (95% CI, 0.41-2.56), and 1.76 (95% CI, 0.62-4.97) for the untreated severe OSA group, CPAP-treated group, and untreated mild-moderate OSA group, respectively. No associations were shown between any of the different OSA groups and coronary heart disease incidence. Conclusions- The incidence of stroke, but not coronary heart disease, is increased in elderly patients with untreated severe OSA. Adequate CPAP treatment may reduce this risk.

Soluble PD-L1 is a potential biomarker of cutaneous melanoma aggressiveness and metastasis in obstructive sleep apnoea patients.

Obstructive sleep apnoea (OSA) upregulates the programmed cell death-1 receptor and its ligand (PD-L1) pathway, potentially compromising immunosurveillance. We compared circulating levels of soluble PD-L1 (sPD-L1) in patients with cutaneous melanoma according to the presence and severity of OSA, and evaluated relationships with tumour aggressiveness and invasiveness.In a multicentre observational study, 360 patients with cutaneous melanoma underwent sleep studies, and serum sPD-L1 levels were assayed using ELISA. Cutaneous melanoma aggressiveness indices included mitotic rate, Breslow index, tumour ulceration, Clark level and tumour stage, and sentinel lymph node (SLN) metastasis was recorded as a marker of invasiveness.sPD-L1 levels were higher in severe OSA compared to mild OSA or non-OSA patients. In OSA patients, sPD-L1 levels correlated with Breslow index and were higher in patients with tumour ulceration, advanced primary tumour stages or with locoregional disease. The incorporation of sPD-L1 to the classic risk factors to SLN metastasis led to net improvements in the classification of 27.3%.Thus, sPD-L1 levels are increased in melanoma patients with severe OSA, and, in addition, might serve as a potential biomarker of cutaneous melanoma aggressiveness and invasiveness in this group of subjects.

Good long-term adherence to continuous positive airway pressure therapy in patients with resistant hypertension and sleep apnea.

Although adequate adherence is paramount in achieving the beneficial effects of continuous positive airway pressure therapy in patients with obstructive sleep apnea, long-term adherence and the variables involved in continuous positive airway pressure compliance in patients with resistant hypertension and obstructive sleep apnea are yet unknown. We conducted a prospective, multicentre, observational study in 177 patients recruited from hypertensive units with resistant hypertension confirmed by means of 24-hr blood pressure monitoring (blood pressure ≥ 130 and/or ≥ 80 mmHg, despite taking at least three antihypertensive drugs or < 130/80 mmHg with > 3 drugs) and obstructive sleep apnea (apnea-hypopnea index ≥ 5 in a respiratory polygraph) who were prescribed continuous positive airway pressure treatment. Good adherence was defined as an average cumulative continuous positive airway pressure use of ≥ 4 hr per night at the end of the follow-up. A multivariate Cox regression analysis was performed to identify independent predictors of continuous positive airway pressure adherence. Patients were followed for a median of 57.6 (42-72) months after initiating continuous positive airway pressure therapy. At the end of the follow-up, the median continuous positive airway pressure use was 5.7 (inter-quartile range 3.9-6.6) hr per night, and 132 patients (74.5%) showed good continuous positive airway pressure adherence. The only baseline variable associated with poor adherence was the presence of previous stroke (hazard ratio 4.00, 95% confidence interval 1.92-8.31). Adequate adherence at 1 month also predicted good adherence at the end of the follow-up (hazard ratio 14.4, 95% confidence interval 4.94-56). Both variables also predicted adherence at a threshold of 6 hr per night. Our results show that good continuous positive airway pressure adherence is an achievable and feasible goal in patients with resistant hypertension and obstructive sleep apnea. Previous stroke and short-term adherence predicted long-term adherence.

Biomarkers of carcinogenesis and tumour growth in patients with cutaneous melanoma and obstructive sleep apnoea.

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h-1), mild OSA (AHI 5-15 events·h-1) and moderate-severe OSA (AHI >15 events·h-1). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable.360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8-68.0) years and AHI 8.55 (2.8-19.5) events·h-1). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate-severe OSA: OR 2.35, p=0.013).In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion.

Effect of continuous positive airway pressure on blood pressure and metabolic profile in women with sleep apnoea.

Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA.A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15 events·h-1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups.Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (-2.04 mmHg, 95% CI -4.02- -0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (-1.54 mmHg, 95% CI -4.58-1.51; p=0.32) and mean blood pressure (-1.90 mmHg, 95% CI -4.0-0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed.In women with moderate-to-severe OSA, 12 weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment.

Continuous Positive Airway Pressure Improves Quality of Life in Women with Obstructive Sleep Apnea. A Randomized Controlled Trial.

RATIONALE: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. OBJECTIVES: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. METHODS: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. MEASUREMENTS AND MAIN RESULTS: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). CONCLUSIONS: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).

A Bayesian cost-effectiveness analysis of a telemedicine-based strategy for the management of sleep apnoea: a multicentre randomised controlled trial.

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. AIM: To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. METHODS: A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. RESULTS: We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.

Efficacy of continuous positive airway pressure treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a randomized controlled trial.

The main purpose of the present analysis is to assess the influence of introducing early nasal continuous positive airway pressure (nCPAP) treatment on cardiovascular recurrences and mortality in patients with a first-ever ischaemic stroke and moderate-severe obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥20 events h(-1) during a 5-year follow-up. Patients received conventional treatment for stroke and were assigned randomly to the nCPAP group (n = 71) or the control group (n = 69). Cardiovascular events and mortality were registered for all patients. Survival and cardiovascular event-free survival analysis were performed after 5-year follow-up using the Kaplan-Meier test. Patients in the nCPAP group had significantly higher cardiovascular survival than the control group (100 versus 89.9%, log-rank test 5.887; P = 0.015) However, and also despite a positive tendency, there were no significant differences in the cardiovascular event-free survival at 68 months between the nCPAP and control groups (89.5 versus 75.4%, log-rank test 3.565; P = 0.059). Early nCPAP therapy has a positive effect on long-term survival in ischaemic stroke patients and moderate-severe OSA.

Role of sleep apnea and continuous positive airway pressure therapy in the incidence of stroke or coronary heart disease in women.

RATIONALE: It is unknown whether obstructive sleep apnea (OSA) may be a risk factor for incident cardiovascular events in women. OBJECTIVES: We sought to investigate whether OSA increases the incidence of a composite of stroke or coronary heart disease (CHD) in women, and the role of continuous positive airway pressure (CPAP) treatment on this association. METHODS: This was a prospective, observational study conducted in two Spanish teaching hospitals between 1998 and 2007. Consecutive women referred for suspected OSA and free of previous stroke and CHD were analyzed. Women with an apnea-hypopnea index (AHI) less than 10 comprised the control group, and those with an AHI greater than or equal to 10 were diagnosed with OSA and classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December 2010. MEASUREMENTS AND MAIN RESULTS: A total of 967 women were studied (median follow-up, 6.8 yr; interquartile range, 5.2-8.2). The untreated OSA group showed a greater incidence rate of the composite outcome than the control group (2.19 vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95% confidence interval [CI], 1.35-5.62) for the untreated OSA group, and 0.91 (95% CI, 0.43-1.95) for the CPAP-treated group. When the type of cardiovascular event was separately assessed, untreated OSA showed a stronger association with incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46-28.3) than with CHD (adjusted hazard ratio, 1.77; 95% CI, 0.76-4.09). CONCLUSIONS: In women, untreated OSA is associated with increased incidence of serious cardiovascular outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce this risk.

Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma.

Some recent studies have shown an association between sleep disordered breathing (SDB) and cancer mortality and incidence but no study has focused on a specific type of cancer. The objective of this study was to analyse the relationship between the severity of SDB and factors related to cutaneous malignant melanoma (CMM) aggressiveness. We performed a multicentre observational study in 82 consecutive patients diagnosed with CMM. 56 patients in whom melanoma measurements were available were finally included in the study. Melanoma measurements of aggressiveness included: tumour mitotic rate, Breslow index, presence of ulceration, stage of disease and growth rate of melanoma. A sleep study was performed in all the included patients. Multivariate analyses were used to examine the independent relationship between SDB severity (apnoea-hypopnea index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and measures of CMM aggressiveness. 60.7% of patients had SDB (AHI ≥ 5) and 14.3% severe obstructive sleep apnoea (AHI ≥ 30). In fully adjusted multivariate analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly correlated with other aggressiveness factors of CMM, such as Breslow index, presence of ulceration and mitotic index. SDB severity markers are associated with some aggressiveness markers of CMM.

Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort.

RATIONALE: Obstructive sleep apnea (OSA) has been associated with increased cancer mortality, but whether it is also associated with cancer incidence is unknown. OBJECTIVES: To investigate whether OSA is associated with increased cancer incidence in a large clinical cohort. METHODS: A multicenter, clinical cohort study including consecutive patients investigated for suspected OSA between 2003 and 2007 in seven Spanish teaching hospitals. Apnea-hypopnea index (AHI) and percent nighttime with oxygen saturation less than 90% (TSat(90)) were used as surrogates of OSA severity, both as continuous variables and categorized by tertiles. Cox proportional hazards regression analyses were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for cancer incidence after adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: A total of 4,910 patients were analyzed (median follow-up, 4.5 yr; interquartile range, 3.4-5.2). Compared with the lower TSat(90) category (<1.2%), the adjusted hazards (95% CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for TSat(90) 1.2-12% and 2.33 (1.57-3.46) for TSat(90) greater than 12%. Continuous TSat(90) was also associated with cancer incidence (adjusted HR, 1.07 [1.02-1.13] per 10-unit increase in TSat(90)). In stratified analyses, TSat(90) was associated with cancer incidence in patients younger than 65 years (adjusted HR, 1.13 [95% CI, 1.06-1.21] per 10-unit increase in TSat(90)) and males (adjusted HR, 1.11 [95% CI, 1.04-1.17] per 10-unit increase in TSat(90)). AHI was not associated with cancer incidence in the adjusted analyses, except for patients younger than 65 years (adjusted HR for AHI >43 vs. <18.7, 1.66; 95% CI, 1.04-2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of OSA severity was associated with increased cancer incidence. This association seems to be limited to men and patients younger than 65 years of age.