Time Spent with Saturation below 80% versus 90% in Patients with Obstructive Sleep Apnoea.

BACKGROUND: Nocturnal hypoxaemia measured as the percentage of total sleep time spent with saturation below 90% (TST90%) may better predict cardiovascular consequences of obstructive sleep apnoea (OSA) than the number of obstructive respiratory events measured with the apnoea-hypopnea index (AHI). Deeper hypoxaemia may potentially induce more severe pathophysiological consequences. However, the additional value of the percentage of total sleep time spent with saturation below 80% (TST80%) to TST90% is not fully explored. METHODS: Comprehensive medical history was taken and fasting lipid and C-reactive protein levels were measured in 797 volunteers participating in two cohort studies in Hungary and Romania. Sleep parameters, including AHI, TST90% and TST80%, were recorded following a polysomnography (PSG, n = 598) or an inpatient cardiorespiratory polygraphy (n = 199). The performance of TST80% to predict cardiovascular risk was compared with TST90% using linear and logistic regression analyses as well receiver operating characteristics curves. Sensitivity analyses were performed in patients who had PSG, separately. RESULTS: Both parameters are significantly related to cardiovascular risk factors; however, TST80% did not show better predictive value for cardiovascular risk than TST90%. On the other hand, patients with more severe hypoxaemia reported more excessive daytime sleepiness. CONCLUSIONS: TST80% has limited additional clinical value compared to TST90% when evaluating cardiovascular risk in patients with OSA.

The link between the sphingolipid rheostat and obstructive sleep apnea.

Chronic inflammation induced by hypoxia during sleep is an important mechanism of microvascular damage in OSA patients. In this study, we investigated the role of the sphingosine rheostat, which has diverse inflammatory effects. Thirty-seven healthy subjects and 31 patients with OSA were recruited. We collected data on demographics and comorbidities. Plasma sphingosine-1-phosphate and ceramide antibody concentrations were measured by ELISA. The results were compared between the OSA and control groups, and the correlations between these measurements and markers of disease severity and comorbidities were explored. Ceramide antibody levels were significantly elevated in OSA patients (892.17 ng/ml) vs. controls (209.55 ng/ml). S1P levels were also significantly higher in patients with OSA (1760.0 pg/ml) than in controls (290.35 pg/ml, p < 0.001). The ceramide antibody concentration showed correlations with BMI (ρ = 0.25, p = 0.04), CRP (ρ = 0.36, p = 0.005), AHI (ρ = 0.43, p < 0.001), ODI (ρ = 0.43, p < 0.001), TST90% (ρ = 0.35, p = 0.004) and the lowest oxygen saturation (ρ =  0.37, p = 0.001) in the whole study population but not when patients with OSA were analyzed separately. The elevated ceramide antibody and sphingosine-1-phosphate concentrations in patients suffering from OSA suggests their involvement in the pathomechanism of OSA and its comorbidities.

Effects of Acute Hypoxia on Heart Rate Variability in Patients with Pulmonary Vascular Disease.

Pulmonary vascular diseases (PVDs), defined as arterial or chronic thromboembolic pulmonary hypertension, are associated with autonomic cardiovascular dysregulation. Resting heart rate variability (HRV) is commonly used to assess autonomic function. Hypoxia is associated with sympathetic overactivation and patients with PVD might be particularly vulnerable to hypoxia-induced autonomic dysregulation. In a randomised crossover trial, 17 stable patients with PVD (resting PaO2 ≥ 7.3 kPa) were exposed to ambient air (FiO2 = 21%) and normobaric hypoxia (FiO2 = 15%) in random order. Indices of resting HRV were derived from two nonoverlapping 5-10-min three-lead electrocardiography segments. We found a significant increase in all time- and frequency-domain HRV measures in response to normobaric hypoxia. There was a significant increase in root mean squared sum difference of RR intervals (RMSSD; 33.49 (27.14) vs. 20.76 (25.19) ms; p < 0.01) and RR50 count divided by the total number of all RR intervals (pRR50; 2.75 (7.81) vs. 2.24 (3.39) ms; p = 0.03) values in normobaric hypoxia compared to ambient air. Both high-frequency (HF; 431.40 (661.56) vs. 183.70 (251.25) ms2; p < 0.01) and low-frequency (LF; 558.60 (746.10) vs. 203.90 (425.63) ms2; p = 0.02) values were significantly higher in normobaric hypoxia compared to normoxia. These results suggest a parasympathetic dominance during acute exposure to normobaric hypoxia in PVD.

Obstructive Sleep Apnoea and Lipid Metabolism: The Summary of Evidence and Future Perspectives in the Pathophysiology of OSA-Associated Dyslipidaemia.

Obstructive sleep apnoea (OSA) is associated with cardiovascular and metabolic comorbidities, including hypertension, dyslipidaemia, insulin resistance and atherosclerosis. Strong evidence suggests that OSA is associated with an altered lipid profile including elevated levels of triglyceride-rich lipoproteins and decreased levels of high-density lipoprotein (HDL). Intermittent hypoxia; sleep fragmentation; and consequential surges in the sympathetic activity, enhanced oxidative stress and systemic inflammation are the postulated mechanisms leading to metabolic alterations in OSA. Although the exact mechanisms of OSA-associated dyslipidaemia have not been fully elucidated, three main points have been found to be impaired: activated lipolysis in the adipose tissue, decreased lipid clearance from the circulation and accelerated de novo lipid synthesis. This is further complicated by the oxidisation of atherogenic lipoproteins, adipose tissue dysfunction, hormonal changes, and the reduced function of HDL particles in OSA. In this comprehensive review, we summarise and critically evaluate the current evidence about the possible mechanisms involved in OSA-associated dyslipidaemia.

Lumbar spine abnormalities in patients with obstructive sleep apnoea.

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland-Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0-3.5/ vs. 0/0-1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.

Triglyceride-Glucose Index in Non-Diabetic, Non-Obese Patients with Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is associated with increased insulin resistance. Triglyceride-glucose index (TyG) is a simple marker of insulin resistance; however, it has been investigated only by two studies in OSA. The aim of this study was to evaluate TyG in non-diabetic, non-obese patients with OSA. A total of 132 patients with OSA and 49 non-OSA control subjects were included. Following a diagnostic sleep test, fasting blood was taken for the analysis of the lipid profile and glucose concentrations. TyG was calculated as ln(triglyceride [mg/dL] × glucose [mg/dL]/2). Comparison analyses between OSA and control groups were adjusted for age, gender, body mass index (BMI) and smoking. TyG was higher in men (p < 0.01) and in ever-smokers (p = 0.02) and it was related to BMI (ρ = 0.33), cigarette pack-years (ρ = 0.17), apnoea-hypopnoea index (ρ = 0.38), oxygen desaturation index (ρ = 0.40), percentage of total sleep time spent with oxygen saturation below 90% (ρ = 0.34), and minimal oxygen saturation (ρ = -0.29; all p < 0.05). TyG values were significantly higher in OSA (p = 0.02) following adjustment for covariates. OSA is independently associated with higher TyG values which are related to disease severity in non-obese, non-diabetic subjects. However, the value of TyG in clinical practice should be evaluated in follow-up studies in patients with OSA.

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea.

Intermittent hypoxia in obstructive sleep apnoea (OSA) is related to inflammation and metabolic abnormalities. Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) is involved in anti-inflammatory and metabolic processes. However, its ligand, calreticulin (CALR) promotes pro-inflammatory responses and apoptosis. Our aim was to analyse the levels of these biomarkers in OSA. We recruited 46 patients with OSA and 30 control subjects. Inpatient sleep study was performed and fasting plasma samples were collected. Triglyceride glucose index (TyG) and atherogenic index of plasma (AIP) were calculated. Plasma sLRP-1 levels were significantly lower in the OSA group compared to the controls (1.67 (0.90-2.11) mg/L vs. 1.99 (1.53-3.51) mg/L; p = 0.04) after adjustment for age, gender, BMI and lipid profile. Plasma sLRP-1 concentrations were inversely related to age (r = -0.29), BMI (r = -0.35), cigarette pack years (r = -0.31), LDL-C (r = -0.34) and triglyceride levels (r = -0.27), TyG (r = -0.37) and AIP (r = -0.27) as well as to the oxygen desaturation index (ODI, r = -0.24; all p < 0.05). BMI (p = 0.01) and ODI (p = 0.04) were independent predictors for low sLRP-1 levels. CALR did not differ significantly between the two groups (0.23 (0.17-0.34) ng/mL vs. 0.24 (0.20-0.36) ng/mL p = 0.76). We detected lower sLRP-1 levels in subjects with OSA which could contribute to metabolic abnormalities associated with this disease.

Coagulation and Fibrinolysis in Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is a common disease which is characterised by repetitive collapse of the upper airways during sleep resulting in chronic intermittent hypoxaemia and frequent microarousals, consequently leading to sympathetic overflow, enhanced oxidative stress, systemic inflammation, and metabolic disturbances. OSA is associated with increased risk for cardiovascular morbidity and mortality, and accelerated coagulation, platelet activation, and impaired fibrinolysis serve the link between OSA and cardiovascular disease. In this article we briefly describe physiological coagulation and fibrinolysis focusing on processes which could be altered in OSA. Then, we discuss how OSA-associated disturbances, such as hypoxaemia, sympathetic system activation, and systemic inflammation, affect these processes. Finally, we critically review the literature on OSA-related changes in markers of coagulation and fibrinolysis, discuss potential reasons for discrepancies, and comment on the clinical implications and future research needs.

Circulating levels of clusterin and complement factor H in patients with obstructive sleep apnea.

Aim: Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. Materials & methods: We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. Results: There was no difference in CFH levels between patients (1099.4/784.6-1570.5/µg/ml) and controls (1051.4/652.0-1615.1/µg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2-763.2/µg/ml vs 276.1/131.0-424.3/µg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Conclusion: Increase in clusterin levels may be protective in OSA by blocking the MAC formation.

Atherogenic Index of Plasma in Obstructive Sleep Apnoea.

BACKGROUND: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity. METHODS: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index. RESULTS: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all p < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score (ρ = 0.19), the apnoea-hypopnoea index (ρ = 0.40) and oxygen desaturation index (ρ = 0.43, all p < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all p > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C. CONCLUSIONS: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C.

Effect of Nocturnal Oxygen on Blood Pressure Response to Altitude Exposure in COPD - Data from a Randomized Placebo-Controlled Cross-Over Trial.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) are particularly vulnerable to hypoxia-induced autonomic dysregulation. Hypoxemia is marked during sleep. In COPD, altitude exposure is associated with an increase in blood pressure (BP) and a decrease in baroreflex-sensitivity (BRS). Whether nocturnal oxygen therapy (NOT) may mitigate these cardiovascular autonomic changes in COPD at altitude is unknown. MATERIALS AND METHODS: In a randomized placebo-controlled cross-over trial, 32 patients with moderate-to-severe COPD living <800 m were subsequently allocated to NOT and placebo during acute exposure to altitude. Measurements were done at low altitude at 490 m and during two stays at 2048 m on NOT (3 L/min) and placebo (3 L/min, ambient air) via nasal cannula. Allocation and intervention sequences were randomized. Outcomes of interest were BP, BRS (from beat-to-beat BP measurement), BP variability (BPV), and heart rate. RESULTS: About 23/32 patients finished the trial per protocol (mean (SD) age 66 (5) y, FEV1 62 (14) % predicted) and 9/32 experienced altitude-related illnesses (8 vs 1, p < 0.05 placebo vs NOT). NOT significantly mitigated the altitude-induced increase in systolic BP compared to placebo (Δ median -5.8 [95% CI -22.2 to -1.4] mmHg, p = 0.05) but not diastolic BP (-3.5 [95% CI -12.6 to 3.0] mmHg; p = 0.21) or BPV. BRS at altitude was significantly higher in NOT than in placebo (1.7 [95% CI 0.3 to 3.4] ms/mmHg, p = 0.02). CONCLUSION: NOT may protect from hypoxia-induced autonomic dysregulation upon altitude exposure in COPD and thus protect from a relevant increase in BP and decrease in BRS. NOT may provide cardiovascular benefits in COPD during conditions of increased hypoxemia and may be considered in COPD travelling to altitude.

Highlights of the ERS Lung Science Conference and Sleep and Breathing Conference 2021 and the new ECMC members.

This article provides a brief description of some of the most remarkable sessions of the @EuroRespSoc Lung Science Conference and the Sleep and Breathing Conference 2021 and presents the new incoming members of the ECMC (@EarlyCareerERS) https://bit.ly/2RSDP40.

Characteristics of Hungarian patients with obstructive sleep apnoea / Obstruktív alvási apnoéban szenvedo betegek jellemzoi hazai beteganyagon.

Összefoglaló. Bevezetés és célkituzés: Az obstruktív alvási apnoe (OSA) a felnott lakosság jelentos részét érinto betegség, mely ismert rizikófaktora a cardiovascularis és metabolicus betegségeknek és a korai halálozásnak. Mindazonáltal kevés magyarországi adat áll rendelkezésre az OSA-ban szenvedo betegek demográfiai és klinikai jellemzoirol, így vizsgálatunk célja ennek bemutatása volt. Módszer: Retrospektív vizsgálatunkban a Semmelweis Egyetem Pulmonológiai Klinikájának Alváslaboratóriumában kivizsgált 394 személy (58 [46-66] év, 73% férfi, testtömegindex [BMI] = 32,5 [29,2-37,5]) adatait elemeztük, akik kitöltötték az Epworth Álmosság Skálát, poliszomnográfiás vizsgálaton estek át; felvettük az anamnézist, és 255 esetben reggeli éhomi vérvétel történt. Eredmények: 282 esetben igazolódott OSA. Ebben a csoportban magasabb volt a férfiak aránya (66 vs. 35%), magasabb volt az életkor (59 [48-66] vs. 47 [39-60] év) és a BMI (32,11 [27,78-37,18] vs. 25,29 [22,04-29,03] kg/m2), magasabbak voltak a C-reaktív protein értékek (3,0 [1,71-5,34] mg/l vs. 1,71 [0,91-3,31] mg/l), illetve a betegek gyakrabban szenvedtek társbetegségekben a kontrollcsoporthoz képest (magas vérnyomás 74% vs. 39%, cukorbetegség 24% vs. 11%, dyslipidaemia 46% vs. 30%, szív- és érrendszeri betegség 22% vs. 5%, szívritmuszavar 27% vs. 16%; minden p<0,05). Bár az OSA valószínusége progresszívan nott az életkorral és az Epworth Álmosság Skála emelkedésével, a trendekben szignifikáns különbségeket észleltünk a férfiak és a nok között (mindketto p<0,05). Ezzel szemben az OSA valószínuségének BMI-függése nemektol független volt (p = 0,94). Következtetés: Az OSA valószínusége progresszívan emelkedik a kor, a BMI és a nappali aluszékonyság függvényében, ugyanakkor ezt befolyásolja a nem is. Közleményünk rámutat a társbetegségek szurésének fontosságára is az OSA különbözo súlyossági fokaiban. Orv Hetil. 2020; 161(50): 2117-2123. INTRODUCTION AND OBJECTIVE: Obstructive sleep apnoea (OSA) is a common disease which is a known risk factor for cardiovascular and metabolic disease and mortality as well. However, the demographic and clinical characteristics of Hungarian patients with OSA are less known. The aim of this study was to describe them. METHOD: We analysed the data of 394 subjects (58 [46-66] years, 73% male, body mass index [BMI] = 32.5 [29.2-37.5]) who attended the Sleep Laboratory of the Department of Pulmonology at Semmelweis University. The volunteers filled out the Epworth Sleepiness Scale, we performed a polysomnography and took medical history. In 255 subjects, fasting blood samples were collected. RESULTS: OSA was diagnosed in 282 cases. This group had higher proportion of males (66 vs. 35%) and comorbidities (hypertension 74% vs. 39%, diabetes 24% vs. 11%, dyslipidaemia 46% vs. 30%, cardiovascular diseases 22% vs. 5%, arrhythmia 27% vs. 16%), the patients were older (59 [48-66] vs. 47 [39-60] years) and had higher BMI (32.11 [27.78-37.18] vs. 25.29 [22.04-29.03] kg/m2) and C-reactive protein levels (3.0 [1.71-5.34] mg/l vs. 1.71 [0.91-3.31] mg/l, all p<0.05). There was a significant relationship between the propensity of OSA along increasing age, BMI and Epworth Sleepiness Scale; however, the relationship depended on gender for age and Epworth Sleepiness Scale (both p<0.05). CONCLUSION: The propensity of OSA increases with age, BMI and symptoms burden and it is affected by the gender. Our study highlights the importance of screening comorbidities in different severity grades of OSA. Orv Hetil. 2020; 161(50): 2117-2123.

The Burden of Associated Comorbidities in Patients with Obstructive Sleep Apnea-Regional Differences in Two Central-Eastern European Sleep Centers.

BACKGROUND: Obstructive sleep apnea (OSA) is usually associated with cardiovascular and cerebrovascular disease, metabolic syndrome and depression. Data on relevant OSA-associated comorbidities in Central-European populations are scarce. The aim of this study was to compare the prevalence of comorbidities in two OSA cohorts from Hungary and Romania. METHODS: Data from 588 (282 from Hungary, 306 from Romania) untreated patients with OSA were retrospectively analyzed. The prevalence rates of hypertension, diabetes, dyslipidemia, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), osteoporosis, cerebrovascular and cardiovascular disease, arrhythmia and depression were compared between the two populations following adjustment for demographics, body mass index, smoking history, comorbidities and sleep parameters. RESULTS: The prevalence rates of hypertension, arrhythmia, cerebrovascular and cardiovascular disease, diabetes and COPD in the whole study population were directly related to the severity of OSA. We found an inverse correlation between the prevalence of osteoporosis and OSA severity (all p < 0.05). Following adjustment, the prevalence of dyslipidemia was higher in the Hungarian cohort, whilst the prevalence of asthma, cardiovascular and cerebrovascular diseases was higher in the Romanian cohort (all p < 0.05). CONCLUSIONS: There was no difference in the prevalence rate of most comorbidities in patients with OSA from the two cohorts, except for dyslipidemia, asthma, cardiovascular and cerebrovascular disease.

The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results.

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31-0.88/ng/mL vs. 0.31/0.31-0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11-59.25/ng/mL vs. 46.83/25.41-89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = - 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.

The Nitric Oxide Pathway in Pulmonary Arterial Hypertension: Pathomechanism, Biomarkers and Drug Targets.

The altered Nitric Oxide (NO) pathway in the pulmonary endothelium leads to increased vascular smooth muscle tone and vascular remodelling, and thus contributes to the development and progression of pulmonary arterial hypertension (PAH). The pulmonary NO signalling is abrogated by the decreased expression and dysfunction of the endothelial NO synthase (eNOS) and the accumulation of factors blocking eNOS functionality. The NO deficiency of the pulmonary vasculature can be assessed by detecting nitric oxide in the exhaled breath or measuring the degradation products of NO (nitrite, nitrate, S-nitrosothiol) in blood or urine. These non-invasive biomarkers might show the potential to correlate with changes in pulmonary haemodynamics and predict response to therapies. Current pharmacological therapies aim to stimulate pulmonary NO signalling by suppressing the degradation of NO (phosphodiesterase- 5 inhibitors) or increasing the formation of the endothelial cyclic guanosine monophosphate, which mediates the downstream effects of the pathway (soluble guanylate cyclase sensitizers). Recent data support that nitrite compounds and dietary supplements rich in nitrate might increase pulmonary NO availability and lessen vascular resistance. This review summarizes current knowledge on the involvement of the NO pathway in the pathomechanism of PAH, explores novel and easy-to-detect biomarkers of the pulmonary NO.

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea.

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apnea (OSA) is associated with an enhanced systemic inflammation and oxidative stress, but mechanisms that regulate these processes are poorly understood. The aim of the study was to investigate the plasma levels of klotho in OSA. Twenty-one previously untreated patients with OSA (56 ± 13 years, 12 males) and 41 non-OSA control volunteers (48 ± 16 years, 8 males) participated in the study. Medical history has been taken; participants filled out the Epworth Sleepiness Scale. C-reactive protein and renal function, glucose and lipid profile measurements were performed in sera; klotho was determined in citrate-treated plasma samples. Levels of plasma klotho were decreased in OSA (519.1 ± 164.9 pg/mL) versus controls (700.8 ± 431.4 pg/mL, p = 0.02). Reduced klotho concentrations were associated with markers of overnight hypoxemia determined with O2 desaturation index (r = -0.31, p = 0.01), percentage of sleep time spent with saturation <90% (r = -0.41, p < 0.01), and minimal saturation during sleep (r = 0.33, p = 0.01). Interestingly, there was no relationship with apnea-hypopnea index, total sleep time, or arousal index (all p > 0.05). Significant association was also found between low plasma klotho levels and the presence of hypertension (p < 0.05). Our results suggest that chronic intermittent hypoxia reduces the levels of klotho in OSA, which may contribute to the development of hypertension. Decreased klotho levels may play a role in enhanced systemic inflammation in OSA and may be a future target for drug development.