Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea.

There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA. 519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR. In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in ε2 carriers and the ε3/ε3 genotype only. Nevertheless, the ε4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk ε4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic ε4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p=0.009 and p<0.001, respectively; R(2)=0.148) and ApoB levels (p=0.001 and p=0.003, respectively; R(2)=0.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA.

Size and subclasses of low-density lipoproteins in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have proatherogenic dyslipidemia. We analyzed predictors of low-density lipoproteins' (LDLs) size in patients with OSA. In a cross-sectional study including 58 participants with OSA (30 without the metabolic syndrome [MetS] and 28 with MetS), we evaluated the size of LDL by gradient gel electrophoresis. Compared with patients without the MetS, those with MetS showed lower LDL size (P = .007), due to a reduction in large LDL-I particles (P = .002) and an increase in small, dense LDL-IIIA (P = .048) and LDL-IIIB (P = .037). The size of LDL correlated inversely with age (r = -.268, P = .042) and serum triglycerides (r = -.364, P = .005), and positively with serum high-density lipoprotein cholesterol levels (r = .335, P = .010). In multiple regression analysis, the presence of the MetS was the only independent predictor of LDL size (P = 0.015). In patients with OSA, MetS is an independent predictor of LDL size and subclasses, whereas the severity of OSA does not contribute independently to alterations in LDL phenotype.

Risk factors and severity of obstructive sleep apnoea in central European Roma and non-Roma patients referred for a diagnostic polysomnography [corrected].

OBJECTIVE: Obesity and metabolic syndrome are common among Roma subjects in Slovakia. We hypothesised that Roma subjects are at high risk to suffer from severe obstructive sleep apnoea (OSA). METHODS: 137 non-Roma and 23 Roma subjects referred for a diagnostic polysomnography were consecutively recruited. Overnight polysomnography, anthropometric variables and standard biochemical analyses were analysed. RESULTS: Obstructive sleep apnoea was diagnosed in 91% Roma and 65% non-Roma subjects (p < 0.001). Roma subjects had higher apnoea-hypopnoea index (AHI) (61.2 ± 7.9 vs. 22.8 ± 2.3 events/h, p < 0.001), lower dip oxygen saturation (56.7 ± 4.9 vs. 79.3 ± 1.3%, p < 0.001), and higher waist circumference as compared to non-Roma subjects (121.3 ± 3.1 vs. 105.2 ± 2.4 cm, p < 0.001). In multiple regression analysis, Roma background (p < 0.001) and waist circumference (p < 0.001) were independent predictors of AHI (R (2) = 0.330). Roma background was associated with significantly higher risk of severe OSA (odds ratio 3.73; 95% confidence interval 1.20-11.65, p = 0.023), independently of age, gender and waist circumference. CONCLUSIONS: Among subjects referred for polysomnography, Roma background is associated with significantly higher risk of severe OSA. Knowledge of common OSA pattern in Roma patients may help in identifying high risk individuals and guide early therapy of this disease.

Predictors of compliance with continuous positive airway pressure treatment in patients with obstructive sleep apnea and metabolic syndrome.

OBJECTIVE: Continuous positive airway pressure (CPAP) applied via a tight-fitting mask is the most effective treatment for obstructive sleep apnea (OSA) and has potential to improve the cardiovascular prognosis in such patients. Adequate compliance with the use of CPAP is essential for achieving the cardiovascular and metabolic benefits of this treatment. This prospective study aimed to assess factors related to objective compliance with CPAP treatment in Slovakian patients with metabolic syndrome and newly diagnosed OSA. PATIENTS AND METHODS: Fifty-one patients (42 men) with metabolic syndrome and OSA (mean age, 54.5 +/- 1.5 years; mean apnea-hypopnea index 59.0 +/- 3.9 events/h of sleep; mean lowest sleep transcutaneous oxygen saturation [SpO(2)] 66.0 +/- 2.7%) underwent pressure titration during overnight polysomnography using the Autoset self-adjusting CPAP device. Metabolic syndrome was diagnosed according to the recent definition of the International Diabetes Federation. Objective compliance was assessed electronically at the 8-week follow-up visit. RESULTS: Obesity was present in all (100%) the patients and arterial hypertension in 48 (94%); fasting plasma glucose levels were increased in 27 (55%) patients and serum triglycerides in 36 (71%); serum HDL cholesterol was reduced in 30 (59%) patients. Two patients did not use CPAP at all and were excluded from further analyses. The remaining 49 patients were divided into two groups: CPAP compliant (>or=4 h/night, mean use 5.52 +/- 0.19 h/night, n = 30) and CPAP non-compliant (< 4 h/night; mean use 1.94 +/- 0.27 h/night, n = 19). Mask leak was significantly higher in the non-compliant patients (43.0 +/- 4.4 vs. 31.9 +/- 2.7 l/min, P = 0.027). No relationships were observed between CPAP compliance and age, apnea-hypopnea index, arousal index or variables of sleep architecture. In contrast, CPAP compliance was significantly related to mean sleep SpO(2) (r = 0.314, P = 0.028), the lowest sleep SpO(2) (r = 0.297, P = 0.038) and mask leak (r = -0.376, P = 0.008). A close relationship between BMI and mask leak was also observed (r = 0.579, P < 0.001). In multiple linear regression analyses with CPAP compliance as an independent variable, and age, sex, mask leak, BMI and mean sleep SpO(2) as dependent variables, mask leak was the only independent predictor of CPAP compliance (R(2) = 0.382, P = 0.009). CONCLUSION: The study demonstrates the relationship between reductions in mask leak and good compliance with CPAP treatment in central European patients with OSA and concurrent metabolic syndrome. Strategies to maintain low leakage of the CPAP mask are warranted, particularly in grossly overweight patients.

Cardiovascular risk and insulin resistance in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) has been linked to cardiovascular and cerebrovascular diseases in previous studies. However, it remains unclear whether OSA relates to cardiovascular outcomes independently of obesity and/or insulin resistance. MATERIAL/METHODS: At a tertiary referral teaching hospital, this cross-sectional analysis of 98 subjects (28 without, 39 with mild-moderate, and 31 with severe OSA) aimed to determine whether OSA relates to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) cardiovascular risk independently of obesity and insulin resistance. OSA was diagnosed by attended polysomnography. The insulin resistance index (HOMA-IR) was based on a homeostasis model assessment method. RESULTS: Of the patients without to those with mild-moderate to those with severe OSA, significant increases were observed in NCEP ATP III risk [median (25%, 75% quartiles) from 2.0 (1.0, 8.0) to 3.0 (1.0, 12.0) to 16.0 (5.3, 20.0)%, p <0.001 for the trend] in association with increases in HOMA-IR (p<0.001), diastolic (p=0.039) and mean blood pressure (p=0.016), serum triglycerides (p=0.047), apolipoprotein B (p=0.039), plasma fibrinogen (p=0.013), and fasting glucose levels (p=0.002). Compared with subjects without sleep apnea, patients with severe OSA had significantly higher odds for NCEP ATP III risk higher than 10% (moderately high and high cardiovascular risk) (odds ratio: 4.06, 95% confidence interval: 1.02-16.25, p=0.048) after adjustment for body mass index and HOMA-IR. CONCLUSIONS: These findings suggest that severe OSA is related to higher cardiovascular risk independently of obesity and insulin resistance.

Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome.

BACKGROUND: The increased risk of atherosclerotic morbidity and mortality in patients with obstructive sleep apnea (OSA) has been linked to arterial hypertension, insulin resistance, systemic inflammation, and oxidative stress. We aimed to determine the effects of 8 weeks of therapy with continuous positive airway pressure (CPAP) on glucose and lipid profile, systemic inflammation, oxidative stress, and global cardiovascular disease (CVD) risk in patients with severe OSA and metabolic syndrome. METHODS: In 32 patients, serum cholesterol, triglycerides, high-density lipoprotein cholesterol, fibrinogen, apolipoprotein A-I, apolipoprotein B (ApoB), high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-alpha, leptin, malondialdehyde (MDA), and erythrocytic glutathione peroxidase (GPx) activity were measured at baseline and after 8 weeks of CPAP. The insulin resistance index (homeostasis model assessment [HOMA-IR]) was based on the homeostasis model assessment method, the CVD risk was calculated using the multivariable risk factor algorithm. RESULTS: In patients who used CPAP for > or = 4 h/night (n = 16), CPAP therapy reduced systolic BP and diastolic BP (p = 0.001 and p = 0.006, respectively), total cholesterol (p = 0.002), ApoB (p = 0.009), HOMA-IR (p = 0.031), MDA (p = 0.004), and TNF-alpha (p = 0.037), and increased erythrocytic GPx activity (p = 0.015), in association with reductions in the global CVD risk (from 18.8 +/- 9.8 to 13.9 +/- 9.7%, p = 0.001). No significant changes were seen in patients who used CPAP for < 4 h/night. Mask leak was the strongest predictor of compliance with CPAP therapy. CONCLUSIONS: In patients with severe OSA and metabolic syndrome, good compliance to CPAP may improve insulin sensitivity, reduce systemic inflammation and oxidative stress, and reduce the global CVD risk.

Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population.

AIM: To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population. METHODS: Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods. RESULTS: In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P=0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P=0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P=0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P=0.006). CONCLUSION: Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.

Oxidative stress in patients with COPD and pulmonary hypertension.

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidant/antioxidant imbalance has also been reported in various forms of pulmonary hypertension. The present study aimed to assess systemic oxidative stress, as reflected by serum malondialdehyde (MDA) concentrations and activities of antioxidant enzymes in erythrocytes [glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in patients with and without pulmonary hypertension secondary to COPD. PATIENTS AND METHODS: Seventy-five patients (58 male) with COPD (mean age 65.1 +/- 1.2 years; mean smoking history 35.6 +/- 3.8 pack-years) were studied. Twenty-one healthy non-smokers served as a control group. Pulmonary function was evaluated with body plethysmography; mean and systolic pulmonary artery pressures (Ppa) were assessed with Doppler echocardiography. Serum concentrations of MDA and activities of GPX, SOD and CAT in washed red blood cells were measured using spectrophotometry. RESULTS: Pulmonary hypertension was present in 28 patients with COPD (systolic Ppa: 46.4 +/- 2.3 mmHg; mean Ppa: 26.0 +/- 1.9 mmHg) and absent in 47 (systolic Ppa: 22.9 +/- 0.8 mmHg; mean Ppa: 13.4 +/- 0.6 mmHg). Compared with the healthy control group, all the patients (with or without pulmonary hypertension) had higher serum MDA concentrations (1.5 +/- 0.1 versus 2.3 +/- 0.1 versus 2.3 +/- 0.1 nmol/mL, ANOVA, P < 0.001) and lower erythrocyte GPX activity (51.3 +/- 3.2 versus 42.2 +/- 2.0 versus 41.3 +/- 2.5 U/g Hb, P = 0.029), whereas SOD (1121.1 +/- 29.0 versus 1032.6 +/- 21.8 versus 1032.7 +/- 36.2 U/g Hb, P = 0.063) and CAT activities (4.9 +/- 0.2 versus 4.6 +/- 0.1 versus 4.7 +/- 0.2 U/g Hb; P= 0.454) were similar. No differences were observed in serum MDA concentrations or activities of GPX, SOD and CAT in erythrocytes between COPD patients with and without pulmonary hypertension. CONCLUSION: The study demonstrates the presence of oxidative/antioxidative imbalance in the systemic circulation in patients with COPD: compared with healthy subjects, COPD patients had higher serum MDA concentrations and lower GPX activity in erythrocytes. The magnitudes of the increase in MDA and reduction in GPX activity were similar in COPD patients with pulmonary hypertension and in those with normal pulmonary artery pressures.