Martina Meszaros

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.

Daytime sleepiness is a cardinal symptom of obstructive sleep apnoea (OSA) and a well-recognised side effect of beta-blockers, therefore patients with OSA under this treatment may have worse sleepiness. However, the interaction between daytime sleepiness and beta-blockers use has not been thoroughly investigated in patients with OSA before. We analysed the data of 2183 individuals (1852 patients with OSA and 331 snorer controls) from 3 countries (Greece, Hungary and Moldova). Medical history, including medication usage and the Epworth Sleepiness Scale (ESS) were recorded. Patients and controls were divided into somnolent (ESS ≥ 11) and non-somnolent (ESS < 11) groups, and the association between-blocker use with the somnolent group was investigated with multivariate logistic regression analysis adjusted for confounders. Sensitivity analyses were performed in each cohort, in the severity subgroups, in patients who did not take statins and in those who had polysomnography as a diagnostic test. There was no relationship between beta-blocker usage and the somnolent OSA (p = 0.24) or control (p = 0.64) groups. These results were similar in sensitivity analyses (all p > 0.05). ESS was related to BMI (ρ = 0.25), total sleep time (ρ = 0.07), AHI (ρ = 0.32), oxygen desaturation index (ρ = 0.33) and minimum oxygen saturation (ρ = – 0.32, all p < 0.05) in OSA, and was higher in patients with hypertension, diabetes and cerebro/cardiovascular disease and those who took statins (all p < 0.05). In general, beta-blockers are not associated with increased daytime sleepiness in OSA. Thus, the diagnosis of OSA should not discourage initiation of beta-blocker treatment, if it is clinically indicated.

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.

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.

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 c...

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.

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.

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.

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.

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.