Obstructive sleep apnoea syndrome and the metabolic syndrome in an internal medicine setting

Background: Obstructive sleep apnoea syndrome (OSAS) is widely accepted as a cardiovascular risk factor. Lately it has been considered in turn as both a component and one of the causes of the metabolic syndrome (MS). Methods: We studied 281 heavy snorers of both sexes consecutively attending a metabolic clinic. Aim was to evaluate the association of OSAS and MS in a large series of patients within an internal medicine setting. Patients underwent a clinical and biochemical work up and performed unattended polysomnography. Results: Of 226 non-diabetic snorers, 48 had primary snoring; 54 mild, 51 moderate, and 73 severe OSAS. A positive association was found between OSAS severity, central obesity indices and the mean metabolic score (p = 0.016). Prevalence of hypertension increased with OSA severity (p = 0.010). Polysomnographic indices were correlated with the metabolic score, insulin levels and central obesity indices. At regression analysis, male sex (t = 3.92; p = 0.000) and waist circumference (t = 3.93; p = 0.000) were independently associated with AHI (apnoea/hypopnoea index), while ODI (oxygen desaturation index) and waist circumference were the independent predictors (t = 2.16; p = 0.033 and t = 3.74; p = 0.000 respectively) of the metabolic score. Prevalence of OSA was 83% in 55 patients with diabetes and 34% had severe OSA. Almost all diabetics with OSA had MS. The metabolic score was higher in diabetic OSA as compared to non-diabetic OSAS (p = 0.000). Conclusions: Our findings show a high prevalence of OSAS among patients referred to a metabolic outpatient clinic because of suspected metabolic disorders and heavy snoring and suggest a strong bidirectional association between OSAS and MS. (C) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

Moderate weight loss decreases oxidative stress and increases antioxidant status in patients with metabolic syndrome

Background. Oxidative stress is enhanced in metabolic syndrome (MetS) and believed to contribute to accelerated atherosclerosis. Weight loss is associated with lowered oxidative stress. Methods. We performed a cross-sectional study in 92 consecutive patients with metabolic syndrome and 80 without. A dietary intervention with moderately low-calorie diet (600 calories/day negative energy balance) was carried out in 53 of metabolic syndrome patients. Oxidative stress, assessed by sNOX2-dp and urinary 8-iso-PGF2α, and antioxidant status, assessed by serum levels of vitamin E and adiponectin, were measured before and after 6 months. Results. Serum vitamin E/cholesterol ratio was significantly lower in metabolic syndrome compared to controls (P 5% (group A) or <5% (group B) weight loss, respectively. Urinary 8-iso-PGF2α (-39.0%), serum sNOX2-dp (-22.2%), adiponectin (+125%), and vitamin E/cholesterol ratio (+129.8%) significantly changed only in A group. Changes in body weight and in serum adiponectin were independent predictors of vitamin E/cholesterol ratio variation. Conclusion. Our findings show that in metabolic syndrome moderate weight loss is associated with multiple health benefits including not only oxidative stress reduction but also enhancement of antioxidant status

Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment

<p>Abstract</p> <p>Background</p> <p>Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.</p> <p>Methods</p> <p>We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6 months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2α and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.</p> <p>Results</p> <p>Patients with severe OSAS had higher urinary 8-iso-PGF2α (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2α (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).</p> <p>Conclusions</p> <p>The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.</p

NOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolate

Background Cocoa seems to exert artery dilatation via oxidative stress inhibition but the mechanism is still unclear. Objectives To investigate whether in smokers, dark chocolate elicits artery dilatation via down-regulation of NOX2, the catalytic core of NADPH oxidase. Methods Flow-mediated dilatation (FMD), oxidative stress (as assessed by urinary isoprostanes excretion), nitric oxide generation (as assessed by serum levels of nitrite/nitrate (NOx)), NOX2 activity (as assessed by blood levels of soluble NOX2 derived peptide (sNOX2-dp)) and serum epicatechin were studied in 20 smokers and 20 healthy subjects (HS) in a crossover, single-blind study. Patients were randomly allocated to 40 g dark chocolate (>85% cocoa) or 40 g of milk chocolate (<= 35% cocoa). FMD, urinary isoprostanes, NOx and sNOX2-dp were assessed at baseline and 2 h after chocolate ingestion. Results Smokers had lower FMD and NOx and higher sNOX2-dp compared to HS. After dark chocolate intake, urinary isoprostanes and sNOX2-dp significantly decreased and FMD and NOx significantly increased in smokers but not in HS. No changes of the above variables were observed after milk chocolate intake. Multiple linear regression analysis showed that in smokers the only independent predictive variable associated with a change in FMD was a change in sNOX2-dp. Serum epicatechin increased in either group only after dark chocolate intake, reaching values higher than 0.1 mu M. Platelets from smokers (n=5), but not from HS (n=5), showed lower p47(phox) translocation to platelet membrane and higher NOx when incubated with 0.1-10 mu M epicatechin. Conclusion Results suggest that in smokers, cocoa enhances artery dilatation by lowering of NOX2 activation

Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome

The aim of this study was to assess whether adherence to a restricted-calorie, Mediterranean-type diet improves endothelial dysfunction and markers of oxidative stress in patients with metabolic syndrome. A moderately low-calorie (600 calories/day negative energy balance), low-fat, high-carbohydrate diet ( or < 5% after 6 months. Group A (n = 23) showed a remarkable decrease in body weight (-6. 8%), body-mass-index (-4. 6%), waist circumference (-4. 8%), HOMA-IR (-27. 2%), plasma glucose, glycosylated haemoglobin, total and LDL-cholesterol, blood pressure, serum NOX2 (the catalytic core of NADPH oxidase) (-22. 2%) and urinary8-isoprostanes (-39. 0%) and an increase of serum NOx (Nitrite/Nitrate) (+116. 8%) and adiponectine (+125. 5%) as compared with those in group B (n = 30). A statistically significant increase in brachial artery flow-mediated dilatation was observed in group A (+24. 7%; p < 0. 001), while no changes were present in group B. Variations of flow-mediated dilatation were statistically and negatively correlated with changes of serum NOX2 levels (p = 0. 04), body-mass-index (p < 0. 01), waist circumference (0. 01), glycosylated haemoglobin (p < 0. 01), LDL-cholesterol (p < 0. 01) and triglycerides (p < 0. 05) and positively correlated with changes of serum NOx (p < 0. 001) and adiponectin (p = 0. 01). The results show that moderate weight loss is able to improve endothelial dysfunction in patients with the metabolic syndrome. The coexistent decrease of NOX2 activation suggests a role for oxidative stress in eliciting artery dysfunction. © 2011 SIMI

NOX2 up-regulation is associated with artery dysfunction in patients with peripheral artery disease.

Objective: Oxidative stress seems to play a role in impairing flow-mediated dilation (FMD) in patients with peripheral artery disease (PAD) but the underlying mechanism is still undefined. We evaluated whether NOX2, the catalytic core of NADPH oxidase, the most important producer of reactive oxidant species (ROS), is implicated in impairing FMD. Methods: We measured FMD, urinary isoprostanes, a marker of oxidative stress, nitric oxide generation by serum levels of nitrite/nitrate (NOx), and serum levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NOX2 activation, in 50 PAD patients and 50 controls. Also, we performed an interventional cross-over study to assess if propionyl-l-carnitine (PLC) (6 g/day), vs. placebo, was able to affect FMD via an oxidative stress-mediated mechanism. Results: Compared to controls, patients with PAD had enhanced sNOX2-dp and isoprostanes and reduced NOx and FMD. Multiple linear regression analysis showed that FMD was independently associated with sNOX2-dp. After PLC infusion FMD increased while sNOX2-dp and isoprostanes significantly decreased; no changes were observed after placebo. In vitro study by incubating platelets or white cells with PLC demonstrated a significant inhibition of p47phox translocation on cellular surface and ROS generated by NOX2 activation. Conclusion: This study suggests that in PAD patients ROS generated by NOX2 contribute to reduce FMD and that the administration of an antioxidant is able to improve arterial dilatation via NOX2 inhibition. © 2012 Elsevier Ireland Ltd