Characteristics of Patients with Obstructive Sleep Apnea at High Risk for Cardiovascular Disease.

Background and Objectives: To evaluate the influence of obstructive sleep apnea (OSA)-related symptoms on prevalent cardiovascular disease (CVD) in a large clinical population of patients. Materials and Methods: A total of 2127 patients (mean age 55 years, 24% women) underwent diagnostic polysomnography and were evaluated using the Epworth sleepiness scale (ESS), the Athens Insomnia Scale (AIS), and the Beck Depression Inventory (BDI). We investigated the predictive value of OSA-associated symptoms for prevalent cardiovascular disease, after adjustment for relevant confounding factors including age, obesity, and co-morbidities. Results: Patients with OSA and CVD were older and had a higher Body Mass Index (BMI); the percentage of obese patients was also higher (83% vs. 70%, p < 0001). They also had greater neck, waist, and hip circumferences and a higher waist-to-hip ratio. Excessive daytime sleepiness (ESS ≥ 10) [odds ratio (95% CI) 1.112 (0.708-1.748), p = 0.64], insomnia symptoms (AIS ≥ 6) [odds ratio (95% CI) 0.748 (0.473-1.184), p = 0.21], frequent awakenings [odds ratio (95% CI) 1.599 (1.019-2.508), p = 0.06], and nocturia [odds ratio (95% CI) 1.359 (0.919-2.009), p = 0.124] were not associated with CVD after adjustment for the previous confounders. On the other hand, depressive symptoms (BDI ≥ 10) independently predicted prevalent CVD [odds ratio (95% CI) 1.476 (1.154-1.887), p = 0.002]. Further analysis in subgroups stratified by age, BMI, and gender demonstrated that depressive symptoms predicted prevalent CVD but only in the subgroup of younger (age group < 60 years), obese (BMI group ≥ 30), and male (OR = 1.959, 95% CI = 1.209-3.175, p = 0.006) OSA patients. Conclusions: OSA patients with CVD were more likely to complain of less typical OSA symptoms and depressive symptoms compared to patients without CVD in this large clinical patient cohort, supportingthecomplexity and heterogeneityof OSA.

Evaluation of Inflammatory Markers in a Large Sample of Obstructive Sleep Apnea Patients without Comorbidities.

Systemic inflammation is important in obstructive sleep apnea (OSA) pathophysiology and its comorbidity. We aimed to assess the levels of inflammatory biomarkers in a large sample of OSA patients and to investigate any correlation between these biomarkers with clinical and polysomnographic (PSG) parameters. This was a cross-sectional study in which 2983 patients who had undergone a polysomnography for OSA diagnosis were recruited. Patients with known comorbidities were excluded. Included patients (n = 1053) were grouped according to apnea-hypopnea index (AHI) as mild, moderate, and severe. Patients with AHI < 5 served as controls. Demographics, PSG data, and levels of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR), and uric acid (UA) were measured and compared between groups. A significant difference was found between groups in hs-CRP, fibrinogen, and UA. All biomarkers were independently associated with OSA severity and gender (p < 0.05). Females had increased levels of hs-CRP, fibrinogen, and ESR (p < 0.001) compared to men. In contrast, UA levels were higher in men (p < 0.001). Our results suggest that inflammatory markers significantly increase in patients with OSA without known comorbidities and correlate with OSA severity. These findings may have important implications regarding OSA diagnosis, monitoring, treatment, and prognosis. This trial is registered with ClinicalTrials.gov number NCT03070769.

Tiotropium Respimat Soft Mist Inhaler versus HandiHaler to improve sleeping oxygen saturation and sleep quality in COPD.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality as a result of various alterations in oxygenation parameters and sleep macro- and micro-architecture. There is a shortage of data to support the efficacy of long-acting inhaled anticholinergic agents in improving these adverse effects, which are known to have a negative impact on clinical outcomes. We aimed to compare the tiotropium Respimat Soft Mist Inhaler and the HandiHaler in terms of their effects on sleeping oxygen saturation (SaO2) and sleep quality in patients with COPD. METHODS: In a randomized, open-label, parallel-group trial involving 200 patients with mild to moderate COPD (resting arterial oxygen tension >60 mmHg while awake), we compared the effects of 6 months' treatment with the two devices on sleeping SaO2 and sleep quality. Overnight polysomnography and pulmonary function testing were performed at baseline and after 6 months' treatment. RESULTS: A total of 188 patients completed the trial. Both groups showed significant improvement in minimum sleep SaO2 and time of sleep spent with SaO2 below 90 (TST90) compared to baseline. The patients using the Respimat had significantly better TST90 than did those using the HandiHaler. Sleep disturbance was highly variable in these patients, but the sleep stage durations were significantly better in the Respimat group. CONCLUSIONS: Sleeping SaO2 can be improved by tiotropium delivered using either the HandiHaler device or the Respimat Soft Mist Inhaler. However, the patients who used the Respimat device had significantly better TST90 and sleep architecture parameters.

Intensive versus standard follow-up to improve continuous positive airway pressure compliance.

We aimed to compare the effect of intensive versus standard interventions on continuous positive airway pressure (CPAP) adherence 2 years after CPAP initiation, as well as on sleepiness, quality of life, depression, hospitalisation and death rate due to cardiovascular disease (CVD). 3100 patients with newly diagnosed sleep apnoea were randomised into the standard group, with usual follow-up care, or the intensive group, with additional visits, telephone calls and education. Subjective daytime sleepiness (Epworth Sleepiness Scale; ESS), quality of life (36-item Short Form Health Survey; SF-36) and the patient's level of depression (Beck Depression Inventory; BDI) were recorded before and 2 years after CPAP initiation, together with CVD hospitalisations and death rate. 2 years after CPAP initiation, the intensive group used CPAP significantly more than the standard group (6.9 versus 5.2 h per night; p<0.001). ESS, SF-36 and BDI scores were also significantly better in the intensive group. Furthermore, the standard group had significantly more deaths and hospitalisations due to CVD. CPAP usage can be improved by both intensive and standard patient support. However, the patients who received intensive CPAP support had significantly better ESS, BDI and SF-36 scores, and lower cardiovascular morbidity and mortality, suggesting that an intensive programme could be worthwhile.

Translation and validation of Berlin questionnaire in primary health care in Greece.

BACKGROUND: The aim of our study was to validate a Greek translation of the Berlin Questionnaire (BQ) for obstructive sleep apnoea syndrome (OSAS) and to explore whether this screening questionnaire could be used to help identify primary care patients at greater risk of having OSAS. METHODS: We recruited 189 patients visiting a primary health care setting on the island of Crete, Greece. They all completed the Greek Version of the BQ. Patients were then referred to a Sleep Disorders Unit for evaluation of suspected sleep-disordered breathing. RESULTS: A PSG study was performed in 129 of the 189 subjects (68.3%). BQ identified 74.4% (n = 96) of the patients as high-risk for OSAS and the remaining 25.6% (n = 33) as low-risk. The sensitivity and specificity of BQ for OSAS diagnosis were 76% and 40%, respectively, for an apnoea-hypopnoea index (AHI) ≥5 per hour but <15 per hour, 84% and 61% for an AHI ≥15 per hour but ≤30 per hour, and 79% and 39% for an AHI >30 per hour. CONCLUSIONS: In conclusion, the Greek Version of the BQ is a useful instrument for identifying patients at risk for OSAS in primary health care in Greece. The findings of our study confirm that such screening tools should be used by primary care clinicians for OSAS prediction.

Impact of the COVID-19 pandemic on positive airway pressure adherence and patients' perspectives in Greece: the role of telemedicine.

STUDY OBJECTIVES: To analyze the impact of national lockdowns in Greece on positive airway pressure adherence, patients' perspectives regarding COVID-19 pandemic and the role of telemedicine. METHODS: 872 obstructive sleep apnea patients from southern and 673 from northern Greece, under positive airway pressure treatment, were evaluated with adherence data available 12 months prior to and 3 months after the first and second lockdown. Telemedicine, locally available as part of a research protocol, was used for patient's follow-up in southern Greece and standard follow-up procedures were implemented in northern Greece. We analyzed the impact of COVID-19 lockdown on positive airway pressure adherence and patients' concerns regarding COVID-19 infection. RESULTS: Significant difference was noted in positive airway pressure adherence as measured by the hours of use at 12 months prior to and at the 3 months after the first lockdown in southern (5.6 vs 6.6, P = .003) and northern Greece (5.3 vs 6.0, P = .03). The proportion of patients with optimal adherence (≥ 6 hours) increased by 18% (P = .004) in southern and by 9% (P = .20) in northern Greece after the first lockdown and remained steady after the second lockdown in both groups. In southern Greece, 23% of patients reported that they were concerned about getting COVID-19 due to obstructive sleep apnea diagnosis, while only 3% reported decreased sleep duration. Moreover, 9% were concerned that the presence of obstructive sleep apnea would make them more susceptible for worse outcome in case of COVID-19 infection. CONCLUSIONS: Our results suggest that maintaining follow-up using telemedicine had a positive influence pointing out the potential role of digital health. CITATION: Bouloukaki I, Pataka A, Mauroudi E, Moniaki V, Fanaridis M, Schiza SE. Impact of the COVID-19 pandemic on positive airway pressure adherence and patients' perspectives in Greece: the role of telemedicine. J Clin Sleep Med. 2023;19(10):1743-1751.

Patients with idiopathic pulmonary fibrosis with and without obstructive sleep apnea: differences in clinical characteristics, clinical outcomes, and the effect of PAP treatment.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is associated with worse mortality and clinical outcome. We aimed to assess differences between patients with IPF with and without OSA and the effect of positive airway pressure treatment on sleep and overall life quality, morbidity, and mortality in these patients. METHODS: Forty-five patients with newly diagnosed IPF underwent polysomnography. Using an apnea-hypopnea index ≥ 15 events/h for OSA diagnosis resulted in 16 patients with IPF and 29 with IPF-OSA. The patients completed the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Functional Outcomes in Sleep Questionnaire, Fatigue Severity Scale, Short Form-36 life questionnaire, and Beck Depression Inventory before and at the end of the follow-up period. RESULTS: Patients with IPF-OSA showed the most severe functional impairments in questionnaires, especially for General Health component of the Short Form-36 life questionnaire (37 vs 58, P = .03). At the 7-year follow-up, 16 (36%) patients had died, 6 (38%) in the IPF group and 10 (35%) in IPF-OSA group. Patients with ≥6-hour positive airway pressure use had better survival compared with patients with <6-hour use (P = .04). Significant improvement was also observed in Epworth Sleepiness Scale (3 vs 6, P = .03), Pittsburgh Sleep Quality Index (5 vs 8, P = .01), and Fatigue Severity Scale (37 vs 48, P = .008) score in patients with ≥4-hour positive airway pressure use. CONCLUSIONS: OSA plays a significant role on clinical features and quality of life in patients with IPF. Effective positive airway pressure treatment results in a significant improvement in sleepiness, fatigue, sleep quality, and mortality. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: CPAP Therapy in Patients With Idiopathic Pulmonary Fibrosis and Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/record/NCT01637831; Identifier: NCT01637831.

Cardiovascular Effect and Symptom Profile of Obstructive Sleep Apnea: Does Sex Matter?

STUDY OBJECTIVES: To evaluate the influence of sex on obstructive sleep apnea (OSA)-related symptoms and prevalent cardiovascular disease (CVD) in a large clinical population of patients. METHODS: A total of 6,716 patients (mean age 52 years, 24% women) had undergone diagnostic polysomnography and completed the Epworth Sleepiness Scale (ESS), Athens Insomnia Scale, and Beck Depression Inventory. We investigated the predictive value of sex on associated symptoms and prevalent cardiovascular disease, after adjustment for relevant confounding factors including age, obesity, and comorbidities. RESULTS: Most of the patients (90%) had OSA (apnea-hypopnea index [AHI] ≥ 5 events/h), and 66% were obese. Women were older than men and had a higher body mass index; however, men had a thicker neck circumference, a higher waist-to-hip ratio, and increased OSA severity (AHI 36 versus 27 events/h, P < .001). Female sex independently predicted prevalent CVD after adjustment for confounders (odds ratio [95% CI] 1.476 [1.154-1.887], P = .002). Men independently were more likely to report driving problems (3.359 [2.470-4.569], P < .001) and excessive daytime sleepiness (ESS ≥ 16) (1.355 [1.036-1.773], P = .027). Furthermore, female sex was an independent predictive factor for depressive symptoms (2.473 [1.831-3.340], P < .001), frequent awakenings (1.703 [1.323-2.192], P < .001), nocturia (1.727 [1.340-2.226], P < .001) and morning headaches (1.855 [1.488-2.326], P < .001). CONCLUSIONS: Females referred for sleep studies were more likely to exhibit CVD and less likely to complain of typical OSA symptoms than males in this large clinical patient cohort.

The Association Between Adherence to Positive Airway Pressure Therapy and Long-Term Outcomes in Patients With Obesity Hypoventilation Syndrome: A Prospective Observational Study.

STUDY OBJECTIVES: To assess the role of different levels of adherence and long-term effects of positive airway pressure (PAP) therapy on gas exchange, sleepiness, quality of life, depressive symptoms, and all-cause mortality in patients with obesity hypoventilation syndrome (OHS). METHODS: A total of 252 patients with newly diagnosed OHS were followed up for a minimum of 2 years after PAP initiation. PAP adherence (h/night) was monitored. Arterial blood gas samples were taken with patients being alert for more than 4 hours after morning awakening. Subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]), quality of life (Short Form 36 [SF-36]) and patient's depressive symptoms (Beck Depression Inventory [BDI]) were assessed before and at the end of the follow-up period, along with all-cause mortality. RESULTS: At the end of the follow-up period (median duration [25th-75th percentile], 30 [24-52] months), PaO2 increased from baseline (72.7 ± 10.3 versus 63.2 ± 10.6, P < .001) and both PaCO2 and HCO3- decreased (43.0 [39.2-45.0] versus 50.0 [46.7-55.4] and 27.5 ± 3.2 versus 31.4 ± 4.2, respectively, P < .001). In addition, PAP therapy significantly improved ESS (7 [4-9] versus 14 [11-16], P < .001), BDI (8.8 ± 4.9 versus 15.5 ± 7.3, P < .001) and SF-36 (82 [78-87] versus 74 [67-79], P < .001) scores. Over the follow-up period 11 patients died. Patients who used PAP for > 6 h/night had significant improvements (P < .05) in blood gases and SF-36 scores than less adherent patients. CONCLUSIONS: Increased hours of use and long-term therapy with PAP are effective in the treatment of patients with OHS. Clinicians should encourage adherence to PAP therapy in order to provide a significant improvement in clinical status and gas exchange in these patients. COMMENTARY: A commenary on this article appears in this issue on page 1455. CLINICAL TRIAL REGISTRATION: Title: PAP Therapy in Patients With Obesity Hypoventilation Syndrome, Registry: ClinicalTrials.gov, Identifier: NCT03449641, URL: https://clinicaltrials.gov/ct2/show/NCT03449641.

Obstructive sleep apnea syndrome and cardiovascular disease: The influence of C-reactive protein.

Obstructive sleep apnea syndrome (OSAS) is a common medical condition, associated with atherosclerosis and cardiovascular disease (CVD). The underlying pathophysiologic mechanisms of this association have not been completely understood and may be multifactorial in origin. A number of studies suggest that inflammatory processes have emerged critical in the pathogenesis of CVD in OSAS. A range of circulating inflammatory molecules has been identified and measured, with a view to assess inflammation and predict vascular damage risk, such as plasma cytokines, adhesion molecules, and C-reactive protein (CRP). CRP is a relevant marker worthy of further study, because not only is elevated in patients with OSAS, but also is rapidly becoming a risk factor for cardiac disease. Furthermore, in selected OSAS patients, aggressive treatment of the disorder may lead to retarding or even improvement of CVD progression. However, still there is a debate on the true correlation between CRP and OSAS, as well as the clinical effect of any reduction after OSAS treatment. Further research is required to define those OSAS patients who will have a considerable reduction with treatment, as well as to understand the significance of the interaction between cardiovascular risk factor and CRP reduction in patients with OSAS.