Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients.

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25-75, with BMI 19.0-53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C-reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1-act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA-negative and OSA-positive patients (p < 0.05). Increased PON1-act was observed in the LL-genotype versus the LM + MM-genotype in the study population (p < 0.05). PON1-act was higher in the OSA-negative compared with OSA-positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1-act and LDL-cholesterol in the entire study population. The OSA-positive group presented an inverse relationship between PON1-act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.

Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis.

The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) has been an issue of great concern. The primary purpose of this study was to determine the influence of OSA on the levels of liver enzymes including alanine transaminase (ALT) and aspartate transaminase (AST). The secondary purpose was to estimate the effect of OSA on the histological lesions of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration, fibrosis, as well as NAFLD activity score (NAS). A systematic literature review using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007 to April 2017 was performed, and 9 studies (2272 participants) that met the selection criteria were evaluated. The present study demonstrated that OSA was related to ALT levels, but no significant correlation was found with AST levels. The subgroup analysis showed that the severity of OSA was associated with ALT levels, not with AST levels. The meta-regression analysis showed that age, sex, homeostasis model assessment, diabetes mellitus, body mass index, and waist circumference did not have a significant effect on the levels of ALT and AST. OSA was also found to be significantly correlated with steatosis, lobular inflammation, ballooning degeneration, and fibrosis, but was not correlated with NAS. OSA was independently related to the development and progression of NAFLD in terms of liver enzyme level and histological alterations. Future studies should investigate the possible relevant mechanisms, thereby guiding the exploration of potential therapeutic implications to prevent the progression of disease.

Treatment of obstructive sleep apnoea-hypopnea syndrome by mandible advanced device reduced neuron apoptosis in frontal cortex of rabbits.

Objective: To investigate effects of mandible advanced device (MAD) therapy for obstructive sleep apnoea-hypopnea syndrome (OSAHS) on the neuron apoptosis and acetylcholine esterase activity in frontal cortex. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups (n = 10 in each group): group OSAHS, group MAD, and control group. Hydrophilic polyacrylamide gel was injected into soft palate of the animals to induce OSAHS in group OSAHS and group MAD. The group MAD animals wore MAD to relief the obstructiveness. The control group was not given any treatment. Computed tomography (CT) examination of the upper airway and polysomnography (PSG) recordings were performed in supine position. All rabbits were induced to sleep in a supine position for 4 to 6 hours every day and were observed for consecutive 8 weeks. The frontal cortices of three groups were dissected and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry. Acetylcholine esterase (AchE) activity in the frontal cortex was measured by spectrophotometry. Results: The group OSAHS exhibited high neuron apoptosis rate and low AchE activity than those of group MAD and control group. The blood oxygen saturation was negatively correlated with neuronal apoptosis rate and positively correlated with AchE activity. Applying MAD in OSAHS animals significantly improve the neuronal damage and function deficits by apnoea-hypoxia caused by narrowed upper airway. Conclusion: This study provided evidence that MAD therapy for OSAHS can significantly decrease neuronal apoptosis and increase AchE activity in the frontal cortex.

Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients.

OBJECTIVE: We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes. METHODS: A cross-sectional study in a population of 1744 patients referred for OSA suspicion was conducted. The following variables were determined: glucose, cholesterol, triglycerides, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio (WHR), and overnight sleep study. RESULTS: The 483 patients with GGT ≥40 IU/l were younger and more obese, and had a pattern of more centrally distributed fat than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed more alcohol, had a poorer biochemical profile, and had more respiratory and oximetric alterations during sleep. GGT levels were significantly correlated with AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol, triglycerides, and grams of alcohol consumed per day predicted GGT levels ≥40 IU/l, while none of the polygraphic variables had predictive value. CONCLUSIONS: High GGT levels were associated with the severity of OSA. However, this relationship seems to be due to the coexistence of other associated factors, mainly central obesity, rather than to the respiratory disorders found in this disease.

Circulating microparticles from patients with obstructive sleep apnea enhance vascular contraction: mandatory role of the endothelium.

Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep associated with oxygen desaturation and sleep disruption. We evaluated the role of circulating microparticles (MPs) from patients with OSA in the regulation of vascular function. MPs from whole blood from patients with OSA or control subjects were injected i.v. into mice. Injection of MPs from patients with OSA induced ex vivo vascular hyperreactivity in aortas with functional endothelium but, in contrast, hyporeactivity in vessels without functional endothelium. Vascular hyperreactivity was blunted in the presence of a nitric oxide synthase inhibitor alone or combined with the cyclooxygenase inhibitor indomethacin. MPs from patients with OSA reduced endothelial nitric oxide synthase activity and nitric oxide production, increased aortic cyclooxygenase-1 and cyclooxygenase-2 expression, and increased thromboxane A(2) and prostacyclin production. Blockade of thromboxane A(2) receptor did not affect the serotonin response in arteries from OSA MP-treated mice. A superoxide dismutase mimetic reduced the vascular hyperreactivity induced by MPs from patients with OSA but had no effect on contraction in vessels from control and non-OSA MP-treated mice. These data provide evidence that circulating MPs from patients with OSA induce ex vivo vascular hyperreactivity with the obligatory role of the endothelium and subtle interactions between the nitric oxide and cyclooxygenase pathways and metabolites. These results highlight the participation of MPs in vascular dysfunction associated with OSA.

Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling.

BACKGROUND: Prolonged neutrophil survival is evident in various cardiovascular and respiratory morbidities, in hypoxic conditions in-vitro and in patients with obstructive sleep apnea (OSA) characterized by nightly intermittent hypoxia (IH). This may lead to persistent inflammation, tissue injury and dysfunction. We therefore investigated by a translational approach the potential contribution of the intrinsic stress-induced mitochondrial pathway in extending neutrophil survival under IH conditions. Thus, neutrophils of healthy individuals treated with IH in-vitro and neutrophils of OSA patients undergoing nightly IH episodes in-vivo were investigated. Specifically, the balance between pro-apoptotic Bax and anti-apoptotic Mcl-1 protein expression, and the potential involvement of p38MAPK and ERK1/2 signaling pathways in the control of Mcl-1 expression were investigated. METHODS: Purified neutrophils were exposed to IH and compared to normoxia and to sustained hypoxia (SH) using a BioSpherix-OxyCycler C42 system. Bax and Mcl-1 levels, and p38MAPK and ERK1/2 phosphorylation were determined by western blotting. Also, Bax/Mcl-1 expression and Bax translocation to the mitochondria were assessed by confocal microscopy in pre-apoptotic neutrophils, before the appearance of apoptotic morphology. Co-localization of Bax and mitochondria was quantified by LSM 510 CarlZeiss MicroImaging using Manders Overlap Coefficient. A paired two-tailed t test, with Bonferroni correction for multiple comparisons, was used for statistical analysis. RESULTS: Compared to normoxia, IH and SH up-regulated the anti-apoptotic Mcl-1 by about 2-fold, down-regulated the pro-apoptotic Bax by 41% and 27%, respectively, and inhibited Bax co-localization with mitochondria before visible morphological signs of apoptosis were noted. IH induced ERK1/2 and p38MAPKs phosphorylation, whereas SH induced only p38MAPK phosphorylation. Accordingly, both ERK and p38MAPK inhibitors attenuated the IH-induced Mcl-1 increase. In SH, only p38MAPK inhibition decreased Mcl-1 expression. Similar to neutrophils of healthy subjects exposed to IH (0.97± 0.2), in OSA neutrophils, Bax/Mcl-1 ratio was significantly lower compared to normoxic controls (1.0±0.5 vs.1.99±0.3, p=0.015), and Bax did not co-localize with mitochondria. CONCLUSIONS: These findings suggest that decreased Bax/Mcl-1 balance promotes neutrophil survival in IH in-vitro as well as in OSA patients. Moreover, Bax/Mcl-1 protein function in IH and SH might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.

The relation between Lp-PLA2 levels with periodic limb movements.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2), a novel marker of vulnerable plaque to prone rupture, is a predictor of both cardiovascular event and cerebrovascular event, and highly sensitive-C-reactive protein (hs-CRP) is an acute-phase response protein implicated in a broad range of cardiovascular diseases. We aimed to examine the association between periodic limb movements in sleep (PLMs) with circulating Lp-PLA2 and hs-CRP levels in patients with PLMs. METHODS: Seventy patients with newly diagnosed PLM with polysomnography were enrolled this study. Patients were divided into two groups according to PLM index (normal PLM index, <15; elevated PLM index, ≥15). Lp-PLA2 and hs-CRP concentrations were measured in serum samples by turbidimetric and nephelometric methods, respectively. The concentrations of these parameters were compared between two groups and correlation analysis was performed between PLMs and Lp-PLA2 and hs-CRP levels. RESULTS: Lp-PLA2 levels and hs-CRP were significantly increased in elevated PLM index group compared with the control group (206.8 ± 78.1 vs 157.8 ± 56.7, p = 0.003, and 4.2 ± 3.5 vs 2.4 ± 2.1, p = 0.02, respectively). PLM index was positively correlated with Lp-PLA2 levels (r = 0.40, p = 0.001) and hs-CRP (r = 0.24, p = 0.05). In the linear regression model, Lp-PLA2 was an independent predictor of PLM index (R(2) = 0.36, p = 0.005). CONCLUSION: This study demonstrated an independent linear relation between PLM index and Lp-PLA2. In addition, it was seen increased Lp-PLA2 and hs-CRP levels in patients with elevated PLM index. Based on these results, we can suggest that risk of vascular events may be increased in patients with PLMs and with increased PLM index.

The association among lipoprotein-associated phospholipase A2 levels, total antioxidant capacity and arousal in male patients with OSA.

BACKGROUND: The mechanisms of the increased cardiac and vascular events in patients with OSA are not well understood. Arousal which is an important component of OSA was associated with increased sympathetic activation and electrocardiographic changes which prone to arrhythmias. We planned to examine the association among arousal, circulating Lp-PLA2 and total antioxidant capacity in male patients with OSA. METHODS: Fifty male patients with newly diagnosed OSA were enrolled the study. A full-night polysomnography was performed and arousal index was obtained. Lp-PLA2 concentrations were measured in serum samples with the PLAC Test. Total antioxidant capacity in patients was determined with Antioxidant Assay Kit. RESULTS: Arousal was positively correlated with LP-PLA2 levels (r=0.43, p=0.002) and was negatively correlated with total antioxidant capacity (r= -0.29, p=0.04). Elevated LP-PLA2 levels and decreased total antioxidant activities were found in the highest arousal quartile compared with the lowest and 2nd quartiles (p=0.02, p=0.05, respectively). LP-PLA2 was an independently predictor of arousal index in regression model (ß=0.357, p=0.002) CONCLUSIONS: This study demonstrated a moderate linear relationship between arousal and LP-PLA2 levels. Also, total antioxidant capacities were decreased in the higher arousal index. Based on the study result, the patients with higher arousal index may be prone to vascular events.

Biochemical oxidative stress-related markers in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a condition contributing to oxidative stress. The aim of this study was to ascertain if there is any connection between OSA and novel oxidative stress-related markers. Matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), high sensitive C-reactive protein (hsCRP), pregnancy-associated plasma protein-A (PAPP-A), soluble receptors for advanced glycation end-products (sRAGE), zinc (Zn) and copper (Cu) were measured. Further biochemical markers were evaluated. MATERIAL/METHODS: Fifty-one men suspected for OSA indicated for night polygraphy were included. Apnea/hypopnea index (AHI), oxygen desaturation index (ODI), mean blood hemoglobin oxygen saturation (SpO2) and time of blood hemoglobin oxygen saturation below 90% (SpO2 <90%) were measured. Morning venous blood samples were taken. RESULTS: For body mass index (BMI) we found strong positive correlation with levels of Cu, MMP-9, hsCRP and fibrinogen, and negative correlation with sRAGE. Concerning ventilation parameters, we found positive correlation of ODI and SpO2 <90% with markers MMP-9 and hsCRP. sRAGE level correlated with AHI and ODI negatively. SpO2 correlated negatively with Cu, MMP-9, hsCRP and fibrinogen. There was no correlation between ventilation parameters and markers MMP-2, PAPP-A and Zn. Compared to severity of OSA, there was significant difference in levels of hsCRP and Cu between patients with AHI ≤5 and AHI ≥30 independent of BMI. CONCLUSIONS: MMP-9, hsCRP, sRAGE and Cu seem to be strong predictors of oxidative stress in OSA patients. The strong correlation between oxidative stress-related markers and OSA is elucidated by connection of these to BMI, which is probably a primary condition of oxidative stress, but OSA is an additive condition.

Transcriptomic analysis identifies phosphatases as novel targets for adenotonsillar hypertrophy of pediatric obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) is a highly prevalent disorder in children, in which enlarged adenotonsillar tissues (AT) play a major pathophysiologic role. Mechanisms leading to the proliferation and hypertrophy of AT in children who subsequently develop OSA remain unknown, and surgical extirpation of AT is associated with potential morbidity and mortality. OBJECTIVES: We hypothesized that a computationally based analysis of gene expression in tonsils from children with OSA and children with recurrent tonsillitis without OSA can identify putative mechanistic pathways associated with tonsillar proliferation and hypertrophy in OSA. METHODS: Palatine tonsils from children with either polysomnographically documented OSA or recurrent infectious tonsillitis were subjected to whole-genome microarray and functional enrichment analyses followed by significance score ranking based on gene interaction networks. The latter enabled identification and confirmation of a candidate list of tonsil-proliferative genes in OSA. MEASUREMENTS AND MAIN RESULTS: In vitro studies using a mixed tonsil cell culture system targeting one of these candidates, phosphoserine phosphatase, revealed that it was more abundantly expressed in tonsils of children with OSA, and that pharmacological inhibition of phosphoserine phosphatase led to marked reductions in T- and B-lymphocyte cell proliferation and increased apoptosis. CONCLUSIONS: A systems biology approach revealed a restricted set of candidate genes potentially underlying the heightened proliferative properties of AT in children with OSA. Furthermore, functional studies confirm a novel role for protein phosphatases in AT hypertrophy, and may provide a promising strategy for discovery of novel, nonsurgical therapeutic targets in pediatric OSA.

Insertion/deletion polymorphism and serum activity of the angiotensin-converting enzyme in Turkish patients with obstructive sleep apnea syndrome.

This study determined the allelic frequency and genotypic distribution of an angiotensin-converting enzyme (ACE) polymorphism and serum ACE activity in Turkish patients with obstructive sleep apnea syndrome (OSAS). A colorimetric assay measured serum ACE activity in 73 of 97 subjects. Frequencies for II, ID, and DD genotypes were 19.6, 53.6, and 26.8% in the OSAS group and 15, 38, and 47% in the control group, respectively (P = 0.02). The I allele frequency was higher in the OSAS group than in the healthy control group (P = 0.02). Carrying the I allele (II or ID genotypes) increased OSAS risk 2.41 times in the Turkish population. Mean ACE activity was significantly lower in patients with the II genotype than in the DD genotype (P = 0.011), and ACE activity was significantly lower in patients with severe OSAS than in those with mild OSAS (P = 0.006). Our results suggest that II and ID genotypes of the ACE gene increase the risk of developing OSAS in the Turkish population.

Lack of association of ACE gene I/D polymorphism with obstructive sleep apnea syndrome in Turkish patients.

Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are reports in the literature describing its role in the development of cardiovascular system diseases, with I/D polymorphism of the ACE gene. We examined the relationship between a patient group with obstructive sleep apnea syndrome (OSAS) and a control group in terms of I/D polymorphism of the ACE gene. We examined 64 patients, with 37 individuals serving as the control group. PCR was used to detect ACE I/D gene polymorphism. Genotype was determined according to the bands that formed on agarose gel electrophoresis. Among the 64 OSAS patients, 27 were identified with the ID genotype, 27 with the DD genotype and 10 with the II genotype; among the 37 control subjects, 19 were identified with the ID genotype, 11 with the DD genotype and 7 with the II genotype. When the case group and controls were compared in terms of ID, II and DD genotypes, no significant difference was observed. On the other hand, when the two groups were compared with respect to mean body mass index, the OSAS group was found to be significantly different from the control group (P = 0.009). We conclude that ACE I/D gene polymorphism is not a genetic risk factor for OSAS in Turkish patients.

Continuous positive airway pressure and liver enzymes in obstructive sleep apnoea: data from a randomized controlled trial.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) has been suggested to be an independent risk factor for non-alcoholic fatty liver disease (NAFLD), possibly via intermittent hypoxia that influences blood pressure, lipid levels and insulin resistance, factors themselves known to cause NAFLD. In observational studies, OSAS has been associated with elevated levels of liver enzymes. Continuous positive airway pressure (CPAP) is the treatment for OSAS, but the effects of CPAP on liver enzymes have not been studied in a randomized controlled trial. OBJECTIVE: To determine if 4 weeks of CPAP influence alanine-aminotransferase (ALT) and aspartate-aminotranferase (AST) levels. METHODS: 94 patients with moderate-to-severe OSAS were randomized to therapeutic or sub-therapeutic CPAP treatment. Plasma ALT and AST were measured before and after 4 weeks of CPAP. RESULTS: Results are means +/- SD. ALT levels decreased from 39.1 +/- 26.3 to 30.3 +/- 16.4 IU/l in patients treated with therapeutic CPAP, but also decreased from 36.9 +/- 20.7 to 31.5 +/- 16.5 IU/l in patients treated with sub-therapeutic CPAP (difference between mean changes -3.4, 95% CI -7.8 to 1.0 IU/l, p = 0.13 between groups). AST levels did not change significantly with therapeutic CPAP (from 29.1 +/- 14.7 to 30.2 +/- 13.6 IU/l), nor with sub-therapeutic CPAP (from 28.2 +/- 16.2 to 29.5 +/- 12.6 IU/l; difference between mean changes -0.2, 95% CI -3.0 to 2.6 IU/l, p = 0.87 between groups). CONCLUSIONS: Four weeks of active CPAP has no beneficial effect on aminotransferase levels when compared to sub-therapeutic CPAP in patients with OSAS. Therefore, CPAP does not seem to improve biochemical markers of potential NAFLD in OSAS patients.

Role of nitric oxide synthase gene intron 4 and exon 7 polymorphisms in obstructive sleep apnea syndrome.

The objective of our study was to assess the association of eNOS4 and eNOS296 polymorphisms of endothelial nitric oxide synthase (eNOS) gene with obstructive sleep apnea syndrome (OSAS). Forty-eight patients with OSAS and 181 healthy volunteers were included in the study. Genotype analyses were performed for eNOS intron 4 VNTR and exon 7, Glu298Asp (G --> T) polymorphisms. There was no significant difference between the patients and controls regarding eNOS4 polymorphism (P > 0.05). There was a significant difference between the patients and controls regarding eNOS296 polymorphism. Glu/Asp variant was more frequent whereas Glu/Glu variant was less frequent in the patients compared to controls (P < 0.001). There was no relationship between eNOS4 and eNOS296 polymorphisms and polysomnography parameters, apnea-hypopnea index, age, gender, body weight and height, body mass index, hypertension, coronary artery disease, arrhythmia, diabetes mellitus, hypercholesterolemia and smoking (P > 0.05). The eNOS4 polymorphism of NOS gene is not associated with OSAS. However, eNOS296 polymorphism of NOS gene is associated with occurrence of OSAS, but not with severity of OSAS.

Distribution of common methylenetetrahydrofolate reductase gene mutations in patients with obstructive sleep apnoea.

Homocysteine levels have been investigated in patients with obstructive sleep apnoea syndrome (OSAS), a syndrome associated with a high level of comorbid cardiovascular disease (CVD). While significant increases in homocysteine levels have been observed in OSAS patients with CVD, no increases have been noted in OSAS patients without CVD. This study was designed to investigate the methylenetetrahydrofolate reductase (MTHFR) gene, which is essential for homocysteine metabolism and has been shown to have a causal role in the development of CVD. Eighty subjects, 30 diagnosed with OSAS by polysomnography and 50 controls (healthy volunteers with no symptoms of OSAS) were enrolled. Two mutations in the MTHFR gene were investigated using polymerase chain reactions and restriction fragment length polymorphisms. No significant differences were found in mean age, body mass index, homocysteine levels, or MTHFR allele or genotype distributions between patient and control groups.

Mandibular width as a novel anthropometric measure for assessing obstructive sleep apnea risk.

Craniofacial abnormalities are a known obstructive sleep apnea (OSA) risk factor, but still need to be better characterized. This study investigates the relationship between mandibular width and the risk of developing OSA.We retrospectively analyzed 3D reconstructions of head and neck computed tomography (CT) scans at our institution for mandibular width, neck circumference, neck fat volume (NFV), airway volume (AWV), and NFV:AWV ratio. Age, gender, and BMI were also documented. Patients were contacted to complete a STOP-BANG survey to assess OSA risk. Only patients with reconstructable scans and completed STOP-BANG questionnaires were included in the study. Survey results were analyzed to assess the correlation between mandible width and STOP-BANG. Mandible association was also compared to the associations of the other known risk factors.The final analysis included 427 patients with a mean age of 58.98 years (standard deviation = 16.77), 56% of whom were male. Mandibular width was found to positively correlate with STOP-BANG score (r = .416, P < .001). Statistically significant differences between mandible size for each risk group was seen (P < .001). After controlling for age and sex, mandible size was significantly different only for the low risk vs. high risk groups (odds ratio = 1.11; 95% confidence interval = 1.03-1.20; P = .007). Furthermore, when stratified according to mandible size, the small mandible group (<77.50 mm) predominantly consisted of low risk patients; the medium size mandible group (77.50-84.40 mm) was predominated by intermediate risk patients, and large mandible (>84.40 mm) was predominantly seen in high risk patients. Mandible width expressed a stronger association than NFV:AWV ratio, but neck circumference and NFV had stronger associations than did mandible width.In addition to previously documented OSA risk factors, mandibular width is positively correlated with OSA as an independent risk factor. Observation of a wide mandible (jaw) should raise awareness of OSA risk and increase screening methods when appropriate.

[Erectile dysfunction and obstructive sleep apnea syndrome].

Of 72 patients with obstructive sleep apnea syndrome (OSAS) 32 had erectile dysfunction (ED). OSAS patients with erectile dysfunction had hypogonadism in 24 cases, in 8 men testosterone level was normal. A polysomnographic investigation with monitoring of nocturnal spontaneous erections showed that 32 patients had severe sleep fragmentation with reduced or complete absence of REM and deep sleep phases. In nocturnal penile tumescencia quantitative and qualitative characteristics were abnormal suggesting organic nature of erectile dysfunction in these patients. Eight ED and OSAS patients with normal testosterone received standard OSAS therapy with administration of FDE-5 type inhibitors. Six months later improvement of the erectile function was observed in 6 patients. OSAS patients with hypogonadism were divided into 2 groups. Group 1 (n = 5) received CPAP therapy and group 2 (n = 19) received OSAS standard therapy. Group 2 was treated with inhibitors of FDE-5 type. Three months later improvement of erectile function was seen only in 8. Group 1 received the inhibitors and testosterone replacement. Three months later all 5 patients had no ED complaints, their testosterone was normal. It is recommended to perform monitoring of nocturnal spontaneous erections in the algorithm of examination of all men with OSAS. All patients with OSAS, ED and documented hypogonadism need testosterone replacement therapy if its level persists low despite adequate therapy of OSAS.

Gamma-glutamyl transferase activity as a predictive marker for severity of obstructive sleep apnea syndrome and concomitant hypertension.

BACKGROUND: Chronic intermittent hypia, inflammation and oxidative stress are involved in resultant obstructive sleep apnea syndrome (OSAS), which may affect numerous regulatory mechanisms that play a role in the regulation of blood pressure. Gamma-glutamyl transferase (GGT) is a novel marker in the prediction of cardiovascular risk. OBJECTIVE: The objective of this study was to investigate the correlation of serum levels of GGT with hypertension and the degree of the upper airway obstruction in subjects with OSAS. METHODS: A total of 270 subjects that met the inclusion criteria were enrolled in the study. The subjects were divided into four separate groups according to the apnea-hypopnea index (AHI) scores as the control group (AHI < 5), mild OSAS group (AHI 5-15), moderate OSAS group (AHI 16-30) and severe OSAS group (AHI >30). A further classification of the OSAS subjects was made in two groups based on the presence of hypertension. RESULTS: The study included 43 control individuals and 59 subjects with mild, 54 subjects with moderate and 114 subjects with severe OSAS. The serum levels of GGT were found to be significantly correlated with OSAS severity (control group: 18 ± 3.3, mild OSAS: 23.6 ± 7.3, moderate OSAS: 26.4 ± 7.5 and severe OSAS: 39.8 ± 12). Serum levels of GGT were found to be significantly higher in OSAS subjects with concomitant hypertension than in the group without associated hypertension (P < .05). The results showed that the adjusted mean GGT under OSA without hypertension (Madj  = 28.76, SE = 0.71) was significantly lower than in cases with OSA with hypertension (Madj  = 42.79, SE = 1.19). CONCLUSION: The present study indicated a strong correlation between high serum levels of GGT and concomitant hypertension in subjects with obstructive sleep apnea. This biomarker may be helpful in grading the severity of obstructive sleep apnea and correlated with hypertension in this population.

Effect of continuous positive airway pressure on liver enzymes in obstructive sleep apnea: A meta-analysis.

BACKGROUND: Previous studies have suggested that obstructive sleep apnea (OSA) was associated with nonalcoholic fatty liver disease (NAFLD). However, the impact of OSA treatment using continuous positive airway pressure (CPAP) on liver enzymes remained controversial. This meta-analysis was conducted to determine whether CPAP therapy could reduce liver enzyme levels. METHODS: Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before December 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of serum ALT and AST was extracted for analysis. A total of five studies with seven cohorts that included 192 patients were pooled into meta-analysis. RESULTS: CPAP was associated with a statistically significant decrease on both ALT and AST levels in OSA patients (WMD = 8.036, 95% CI = 2.788-13.285, z = 3.00, P = .003 and WMD = 4.612, 95% CI = 0.817-8.407, z = 2.38, P = .017, respectively). Subgroup analyses indicated that CPAP therapy was more effective in OSA patients with treatment duration > 3 mo (WMD = 12.374, 95% CI = 2.727-22.020, z = 2.51, P = .012 for ALT and WMD = 7.576, 95% CI = 1.781-13.370, z =2.56, P = .010 for AST). CONCLUSION: This meta-analysis suggested that CPAP was associated with a statistically significant decrease on liver enzymes in OSA patients. Further large-scale well-designed RCTs with long-term follow-up are required to clarify this issue.

Serum heparanase levels are associated with endothelial dysfunction in patients with obstructive sleep apnea.

BACKGROUND AND AIM: Obstructive sleep apnea syndrome (OSAS) is well-known to be associated with high risk for cardiovascular (CV) diseases. Heparanase has been recently shown to be related to increased inflammation and vulnerability of the atherosclerotic plaques. Herein we aimed to investigate the relationships between OSAS, heparanase and endothelial dysfunction. MATERIALS AND METHODS: A total of 120 patients with varying severity of OSAS and 31 controls without OSAS were enrolled. Flow-mediated dilatation (FMD) was measured as an indicator of endothelial dysfunction. Serum heparanase levels were measured with ELISA. RESULTS: Serum heparanase levels increased in a stepwise fashion from controls to patients with more severe OSAS. When FMD was compared with controls and various degrees of severity of OSAS, a stepwise decrease in FMD was observed. Serum heparanase levels were found to be significantly associated with apnea hypopnea index (AHI) (r = .57, P < .001) and FMD (r= -.37, P < .001) in patients with OSAS. Serum heparanase levels were significantly associated with hemoglobin-A1c and body mass index in patients with OSAS. Serum heparanase and uric acid levels were independent predictors of FMD in linear regression analysis (R2 = .506, P < .001; P < .001 and P = .001 respectively). CONCLUSIONS: Serum heparanase levels were significantly increased in patients with OSAS and associated with the severity of OSAS (AHI) and endothelial dysfunction (FMD). Increased heparanase activity in OSAS may be related to increased cardiovascular risk in patients with OSAS.