Vitamin D as a biomarker of health in snoring children: a familial aggregation study.

BACKGROUND: Hypovitaminosis D is a common health problem. The purpose of this study was to investigate the inter-relationship between serum 25(OH)D levels and paternal and maternal vitamin D status in a sample of snoring children. METHODS: We selected 137 participants for whom serum 25(OH)D had been measured and underwent overnight polysomnography evaluation. Serum glucose, lipids, liver enzymes, parathyroid hormone, insulin, and glycated hemoglobin were also measured. Glucose and insulin levels were used to estimate insulin resistance with the homeostasis model assessment (HOMA-IR). RESULTS: Vitamin D insufficiency (<30 ng/mL) and deficiency (<20 ng/mL) were found in 40.9 and 17.5% of children, respectively. After adjustments for age, BMI z-score and seasonality, the odds ratio for risk of vitamin D insufficiency according to the vitamin D status of parents were: OR (95% CI): paternal insufficiency 15.1 (2.7-35.7), p = 0.002; maternal insufficiency 7.2 (2.4-22), p = 0.001. When children with vitamin D deficiency were analyzed separately, serum 25(OH)D concentration was found to be associated with the apnea-hypopnea index (r = -0.647, p = 0.009) and respiratory arousal index (r = -0.669, p = 0.034). CONCLUSIONS: Family patterns of vitamin D could be helpful for the early identification of children at risk of metabolic and/or sleep disturbances and when considering strategies to improve vitamin D status. IMPACT: Family patterns of vitamin D could be helpful for the early identification of snoring children at risk of metabolic and/or sleep disturbances. Significant associations were found between serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and their parents. An inverse association between 25(OH)D levels and OSA severity was detected in deficient vitamin D children. Children with insufficient and deficient vitamin D status tended to have a worse metabolic profile, so strategies are needed to improve vitamin D status.

Obstructive sleep apnea is associated with worse clinical-radiological risk scores of pulmonary embolism.

Obstructive sleep apnea is a risk factor for pulmonary embolism, although its association with pulmonary embolism severity is unknown. Our objective was to study if obstructive sleep apnea is associated with worse pulmonary embolism severity scores and greater extent of arterial obstruction. In consecutive pulmonary embolism patients, we performed respiratory polygraphy and recorded sleep characteristics, classical risk factors for pulmonary embolism and physical activity 6-12 months after the pulmonary embolism episode. Simplified Geneva Prognostic Score and Pulmonary Embolism Severity Index were calculated at the time of the pulmonary embolism diagnosis. The Pulmonary Artery Obstruction Index and the right ventricle to left ventricle diameter ratio were measured by computed tomography pulmonary angiography. We included 120 patients, of whom 45.8% had moderate-severe obstructive sleep apnea (apnea-hypopnea index > 15 hr-1 ). There was a larger proportion of moderate-severe obstructive sleep apnea patients in the third and fourth Pulmonary Artery Obstruction Index quartiles and in the III-V Pulmonary Embolism Severity Index levels compared with apnea-hypopnea index < 15 hr-1 group. However, no differences were found between the proportion of patients with or without moderate-severe obstructive sleep apnea in their stratification by simplified Geneva Prognostic Score. The mean adjusted values of the simplified Geneva Prognostic Score, Pulmonary Embolism Severity Index and Pulmonary Artery Obstruction Index scores were higher in the apnea-hypopnea index > 15 hr-1 group (p < .05). Multiple linear regression analysis identified apnea-hypopnea index as the only independent factor related to Pulmonary Artery Obstruction Index and Pulmonary Embolism Severity Index, whereas desaturation index was associated with simplified Geneva Prognostic Score. Patients with pulmonary embolism and moderate-severe obstructive sleep apnea had greater pulmonary artery obstruction as well as more pulmonary embolism severity, assessed by both the simplified Geneva Prognostic Score and the Pulmonary Embolism Severity Index, compared with patients with apnea-hypopnea index ≤ 15 hr-1 . Moreover, these prognostic indices were independently related to sleep parameters.

High D-dimer levels after stopping anticoagulants in pulmonary embolism with sleep apnoea.

Obstructive sleep apnoea is a risk factor for pulmonary embolism. Elevated D-dimer levels and other biomarkers are associated with recurrent pulmonary embolism. The objectives were to compare the frequency of elevated D-dimer levels (>500 ng·mL(-1)) and further coagulation biomarkers after oral anticoagulation withdrawal in pulmonary embolism patients, with and without obstructive sleep apnoea, including two control groups without pulmonary embolism.We performed home respiratory polygraphy. We also measured basic biochemical profile and haemogram, and coagulation biomarkers (D-dimer, prothrombin fragment 1+2, thrombin-antithrombin complex, plasminogen activator inhibitor 1, and soluble P-selectin).64 (74.4%) of the pulmonary embolism cases and 41 (46.11%) of the controls without pulmonary embolism had obstructive sleep apnoea. Plasmatic D-dimer was higher in PE patients with OSA than in those without obstructive sleep apnoea. D-dimer levels were significantly correlated with apnoea-hypopnoea index, and nocturnal hypoxia. There were more patients with high D-dimer after stopping anticoagulants in those with pulmonary embolism and obstructive sleep apnoea compared with PE without obstructive sleep apnoea (35.4% versus 19.0%, p=0.003). Apnoea-hypopnoea index was independently associated with high D-dimer.Pulmonary embolism patients with obstructive sleep apnoea had higher rates of elevated D-dimer levels after anticoagulation discontinuation for pulmonary embolism than in patients without obstructive sleep apnoea and, therefore, higher procoagulant state that might increase the risk of pulmonary embolism recurrence.

Probe-based confocal laser endomicroscopy imaging of endobronchial hamartomas.

Probe-based confocal laser endomicroscopy (pCLE) is a new technique that can microscopically image the airways in vivo during ordinary flexible bronchoscope procedures. pCLE can visualize the basement membrane of the bronchial epithelium, allowing the study of the different changes in benign or malignant/premalignant bronchial lesions. We present 2 cases of pathology-proven endobronchial hamartoma diagnosed by biopsy which show characteristic images under pCLE examination. The tumor was removed in both cases by rigid bronchoscopy using a diathermy loop and a cryoprobe.

Vitamin D status and parathyroid hormone levels in patients with obstructive sleep apnea.

BACKGROUND: Vitamin D insufficiency and high levels of parathyroid hormone (PTH) appear to be emerging risk factors for metabolic syndrome (MS), diabetes and cardiovascular disease, conditions that occur frequently in patients with obstructive sleep apnea syndrome (OSAS). OBJECTIVES: This study examined whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH were associated with the presence of MS, diabetes and hypertension among an OSAS population. METHODS: A total of 826 patients (635 men and 191 women) with newly diagnosed OSAS were studied. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III clinical criteria. Serum levels of 25(OH)D, PTH, glucose, triglycerides, cholesterol, HDL cholesterol, creatinine and uric acid were determined. RESULTS: In 55.3% of the men and in 63.2% of the women, the serum 25(OH)D level was less than 30 ng/ml (insufficient status). After adjusting for age, sex and seasonality, there was a significant trend of decreasing odds for diabetes [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.33-0.94, ptrend = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, ptrend < 0.001) with increasing vitamin D levels. Higher PTH levels were associated with a higher prevalence of obesity (OR 2.05, 95% CI 1.06-3.09, ptrend < 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, ptrend = 0.049). CONCLUSIONS: These data suggest an inverse association of 25(OH)D with diabetes and MS and a positive association of PTH with obesity and hypertension among patients with OSAS. Based on our observational study, the causative nature of the associations cannot be established. These findings require further examination in prospective studies including clinical trials.

Impaired circadian variation of platelet activity in patients with sleep apnea.

BACKGROUND: Cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSAS). There is evidence that the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population is altered in patients with OSAS. This study investigates potential abnormalities in the circadian profiles of platelet activity in OSAS. METHODS: We studied 37 patients with OSAS [7 of whom were also studied after 3 months on continuous positive airway pressure (CPAP) treatment] and 11 controls. In each subject, we obtained six different blood samples during 24-h period (2200, 0200, 0600, 1000, 1400, and 1800 hours). Platelet activity was determined by flow cytometry immediately after sampling. RESULTS: We found that nocturnal platelet activity was significantly increased in patients with OSAS (p = 0.043) and that effective treatment with CPAP decreased platelet activity in these patients but differences just failed to reach statistical significance (p = 0.063). CONCLUSIONS: OSAS is associated with increased platelet activity during the night, and that this appears to be improved by chronic use of CPAP. These results may contribute to explain the high prevalence of cardiovascular events during sleep in OSAS.

The influence of obesity and obstructive sleep apnea on metabolic hormones.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by excessive daytime sleepiness and repetitive upper airway obstruction episodes during sleep. Clinically, obesity is a major risk factor for developing OSAS. However, OSAS has been associated with hormonal and metabolic alterations that could predispose patients to obesity. The aim of this study was to investigate the independent role of apneas and obesity on plasma levels of metabolic hormones (adiponectin, ghrelin, and leptin) in patients with OSAS. METHODS: We have studied patients with OSAS and controls with and without obesity. All patients were male, had an apnea-hypopnea index of 20/h or greater, and were eligible for nasal continuous positive airway pressure (nCPAP) treatment. Patients were considered obese (n = 28) when their BMI was higher than 30 kg/m(2) and non-obese (n = 21) when it was lower than 27 kg/m(2). Non-obese control subjects (n = 20) were non-snorers with a normal cardiorespiratory sleep study, while obese control subjects (n = 10) were recruited from those obese subjects who were visited in our sleep unit and for whom OSAS was excluded by full polysomnography. A single blood sample was obtained from an antecubital vein in all participants after the completion of the nocturnal sleep laboratory recording. Plasma leptin, adiponectin, and ghrelin levels were determined by radioimmunoassay. RESULTS: The adiponectin, ghrelin, and leptin plasma levels were similar in both patients and controls. There were differences in leptin and adiponectin plasma levels between the obese and non-obese in both patient and control groups. In the case of ghrelin, differences between obese and non-obese subjects were only seen in patients. There were no significant differences in hormone levels between the obese controls and obese patients or between non-obese controls and non-obese patients. After 3 months of nCPAP treatment, adiponectin levels decreased significantly both in obese and non-obese patients, and leptin levels decreased in obese patients. Finally, nCPAP did not reduce ghrelin in either obese or non-obese patients. CONCLUSIONS: The basal levels of leptin, adiponectin, and ghrelin were mostly associated with obesity. We found that sleep apnea was not a determinant factor in leptin, adiponectin, and ghrelin hormonal levels. Interestingly, nCPAP treatment diminishes leptin in obese OSA patients and adiponectin levels in obese and non-obese patients with OSAS.

Surfactant protein D concentration in a pediatric population with suspected sleep disorder.

Obstructive sleep apnea (OSA) affects between 2% and 4% in children and there is a search for new biomarkers that can be useful both in the diagnosis and in the evolution of the disease. The surfactant protein D (SP-D) is a collection that is part of the innate immune system exerting an anti-inflammatory and antimicrobial effect. Thus, the objective of this study was to evaluate the concentration of SP-D in the suspect OSA pediatric population. A total of 178 children were recruited in this prospective study. Blood samples, sleep parameters, feeding habits, anthropometric, sociodemographic, and family data were collected. Specific biochemical determinations were made, and the plasmatic concentrations of SP-D were measured by enzyme-linked immunosorbent assay. We found no statistical correlation between the SP-D concentration and the apnea-hypopnea index (AHI) from the data. Nevertheless, the changes in SP-D levels could be correlated to a large extent by the arousals that often go along with hypopneas (r = -0.258, p = 0.011 unadjusted; r = -0.258, p = 0.014 adjusted by age and body mass inded [BMI] Z-score). Intermittent hypoxia was correlated with C-reactive protein levels (r = 0.547, p < 0.001 unadjusted; r = 0.542, p < 0.001 adjusted by age and BMI Z-score). Although AHI and SP-D did not appear to correlate, a secondary analysis suggests that sleep fragmentation, which is produced by arousals, may do, and further research is needed to determine the mechanisms by which changes in SP-D occur in OSA.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.

Non-synonymous polymorphism in the neuropeptide S precursor gene and sleep apnea.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a complex disease with a strong genetic basis. One of the primary molecular domains affected by OSAS is sympathetic activity. Neuropeptide S (NPS) plays an important role in the regulation of the sleep-wakefulness cycle, anxiety states, and daytime sleepiness. It is important to study neuropeptides related to sympathetic activity regulation and how their function could be modified by genetic variants affecting the expression of these molecules. OBJECTIVES: We investigated the association of the non-synonymous polymorphism rs4751440 in the NPS precursor gene with OSAS and certain variables related to OSAS (daytime sleepiness, body mass index (BMI), insulin resistance, and blood pressure). This polymorphism causes an amino acid substitution in exon 3 of the human NPS precursor gene. PATIENTS AND METHODS: We included 253 OSAS patients and 70 healthy subjects. Genotyping was done by polymerase chain reaction using specific flanking primers and agarose gel electrophoresis. Daytime sleepiness, BMI, plasma levels of high-density lipoprotein, glucose, total cholesterol, insulin, triglycerides, and the homeostasis model assessment index were also determined. RESULTS: A similar genotypic and allelic distribution was found in OSAS patients and controls. The risk of OSAS was not associated with the rs4751440 polymorphism. There was no significant interaction between daytime sleepiness or metabolic variables and the rs4751440 polymorphism. CONCLUSION: Genotypic and allelic frequency distribution of the rs4751440 polymorphism was similar in OSAS patients and controls. In this population-based study, we could not show a significant association between rs4751440 polymorphism and susceptibility to OSAS or certain phenotypes related to OSAS (daytime sleepiness, BMI, systolic blood pressure, and insulin resistance) with the exception of diastolic blood pressure.

Polysomnographic Characteristics of Snoring Children: A Familial Study of Obstructive Sleep Apnea Syndrome.

BACKGROUND AND OBJECTIVES: Available evidence suggests a familial basis for OSA. The aim of the present study was to assess the potential influences of parental OSA in predicting the diagnosis and severity of OSA in snoring children. METHODS: Observational study, we prospectively enrolled 84 children and their parents. A complete nocturnal polysomnography was performed. Children were categorized into 3 severity groups according to the apnea-hypopnea index (AHI<1h-1, AHI≥1h-1 to AHI<5h-1, and AHI≥5h-1). Adults were grouped according two criteria (AHI≥5h-1 and ≥10h-1). RESULTS: There were no significant differences in age, gender, BMI and BMI z-score among groups. Among the children, 54.7% had an AHI≥1h-1 and 21.4% had an AHI≥5h-1. Overall, we observed that 60.7% of fathers and 23.8% of mothers of our population had OSA (AHI≥5h-1). The prevalence of fathers with OSA increases with the children's severity (83% in the group of children with moderate-severe OSA, p=0.035). The odds of having moderate-severe pediatric OSA (AHI≥5h-1) were more than 4 times higher among children with a father with AHI≥5h-1 (OR: 4.92, 95% CI: 1.27-19.06; p=0.021). There was no evidence of any maternal influence on OSA severity among the children studied. CONCLUSIONS: Our findings suggest a high prevalence of OSA among the family members studied with an increased association of childhood OSA with paternal OSA. Prediction of OSA risk among children can be significantly improved by adding data on paternal OSA status.

Impact of Obstructive Sleep Apnea on Gestational Diabetes Mellitus.

INTRODUCTION: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR). METHODS: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h-1. RESULTS: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h-1, p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index. CONCLUSION: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women.

Expression of toll-like receptors 2 and 4 is upregulated during hospital admission in traumatic patients: lack of correlation with blunted innate immune responses.

BACKGROUND: There are reports with conflicting results on the expression of toll-like receptors (TLRs) in trauma patients. In addition, these studies analyzed TLR expression only at patients' hospital admission but not later when complications usually arise. OBJECTIVES: To analyze the surface expression of TLR2 and TLR4 on circulating monocytes from trauma patients during the hospitalization period and to correlate this with cytokine production after stimulation with TLR2 and TLR4 agonists. The phagocytic capacity of monocytes was analyzed at the same time points of TLR expression analysis; to correlate these molecular findings with the presence or absence of infections. METHODS: Prospective and observational study from June 2005 to June 2007. In all analysis, a control group composed of healthy subjects was included. RESULTS: We studied 70 trauma patients admitted to the intensive care unit (ICU) of a tertiary hospital, and 30 healthy volunteers. Blood samples were collected at hospital admission, on day 7 and 14. Forty-four patients (63%) developed at least one episode of infection. Monocytes from trauma patients expressed higher levels of TLR2 and TLR4 than monocytes from control subjects at all time points. Expression of TLR2 and TLR4 in monocytes from those patients who developed any infection was significantly lower than in those patients without infection but still significantly higher than in control subjects. Cellular responses to TLR4 agonist were impaired. Monocytes from traumatic patients phagocytosized less efficiently than monocytes from control subjects. CONCLUSIONS: These results indicate that trauma patients present a dysregulation of the innate immune system that persists during the first 14 days after hospital admission.

Red cell distribution width: a new tool for the severity prediction of sleep apnoea syndrome in children.

INTRODUCTION: Red cell distribution width (RDW) is a parameter included in the complete blood count which informs about the size of the circulating red blood cell population and its distribution. In adults, an increase in RDW was shown to be associated both with obstructive sleep apnoea (OSA) and with an increase in cardiovascular mortality. The aim of this study was to determine whether RDW is a potential biomarker for screening children with moderate-severe OSA. METHODS: An observational study in snoring patients was performed. All patients underwent a sleep study and were classified either as simple snorers (apnoea-hypopnoea index (AHI) <1 event·h-1) or as patients with OSA (mild AHI ≥1 to <5 events·h-1; moderate-severe AHI ≥5 events·h-1). Blood analyses (complete blood count and C-reactive protein) were performed for every individual. RESULTS: A total of 175 individuals were recruited. The mean age was 8.3±3.6 years. Correlation studies between RDW and several sleep-related parameters showed negative significant associations with minimum oxygen saturation, and positive significant associations with oxygen desaturation index (≥3% and ≥4%), AHI and the arousal index. A predictive model for paediatric severe OSA (AHI ≥5 events·h-1) was found based on mean corpuscular haemoglobin concentration (MCHC) <34.9 g·dL-1 and RDW >13.1% values, adjusting for body mass index z-score and age (area under the curve 0.657; p=0.004). In addition, differences were found in eosinophil count and C-reactive protein concentrations among the three subgroups. CONCLUSIONS: In children, RDW stands out as a biomarker associated with the severity of OSA. The use of RDW and MCHC could be a simple but useful tool for the severity prediction of paediatric OSA in snoring patients.

Increased plasma levels of asymmetric dimethylarginine and soluble CD40 ligand in patients with sleep apnea.

BACKGROUND: Cardiovascular (CV) diseases are a leading cause of mortality and they are frequent in patients with the obstructive sleep apnea syndrome (OSAS). OBJECTIVES: In this study we investigated if OSAS influences CV function independently of other CV risk factors frequently present in these patients (e.g. obesity, high blood pressure). METHODS: We compared plasma markers of endothelial dysfunction, asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1), and atherosclerosis progression (soluble fraction of the CD40 ligand, sCD40L) in OSAS patients with (n = 23) and without (n = 18) concurrent CV risk factors, as well as in healthy subjects (n = 23). RESULTS: Plasma ADMA (p < 0.01) and sCD40L (p < 0.05) were abnormally increased in patients with OSAS versus healthy controls, but they were not influenced by the presence or absence of CV risk factors in OSAS. ET-1 levels were not different between the three groups of subjects studied. CONCLUSIONS: OSAS is associated with endothelial injury and atherosclerosis progression independently of other CV risk factors.

Prothrombotic state in children with obstructive sleep apnea.

OBJECTIVE: Increased blood coagulation might be one important mechanism linking obstructive sleep apnea (OSA) with cardiovascular diseases. We tested the association between several hemostatic parameters and sleep breathing-related variables in a representative pediatric population with a clinical suspicion of OSA. METHODS: Polysomnography was performed in 152 snoring children to diagnose OSA. Anthropometric and clinical data were registered and venous blood samples were collected for the measurement of platelet count, plateletcrit, platelet distribution width (PDW), mean platelet volume (MPV), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and C-reactive protein. RESULTS: Children with OSA had significantly higher platelet count, plateletcrit and PDW compared with those without OSA. After controlling for the anthropometric characteristics (age, gender, body mass index (BMI) z-score), platelet count negatively correlated with minimum SaO2 while the plateletcrit correlated with time with SaO2 <90% and MPV correlated with apnea-hypopnea index. PT and PT international normalized ratio correlated with mean SaO2 and aPTT correlated with the oxygen desaturation index. CONCLUSION: Our findings suggest that different OSA-related effects may be factors contributing to an enhanced coagulability in pediatric OSA. Measures reflecting apnea severity and disrupted sleep were associated with clotting factor changes independent of covariates affecting hemostatic function.

Biomarker panel in sleep apnea patients after an acute coronary event.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. METHODS: Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. RESULTS: Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. CONCLUSIONS: The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. CLINICAL TRIAL REGISTRATION: NCT01335087 (clinicaltrials.gov).

Endothelial function and circulating endothelial progenitor cells in patients with sleep apnea syndrome.

BACKGROUND: Endothelial dysfunction and cardiovascular diseases are frequent in patients with obstructive sleep apnea (OSA). Circulating endothelial progenitor cells (EPCs) contribute to repair dysfunctional endothelium and have been related to increased cardiovascular risk. OBJECTIVES: We tested the hypothesis that the number of circulating EPCs may be altered in OSA patients. METHODS: EPCs (CD34+ VEGF-R2+) were isolated and quantified from peripheral blood samples of OSA patients (n = 13) and healthy controls (n = 13) matched for age and sex. All subjects were free of any other known cardiovascular risk factors. The plasma levels of vascular endothelial growth factor (VEGF) were also determined, and the endothelium-dependent and endothelium-independent vascular function was assessed in all subjects. RESULTS: Patients with OSA had lower levels of EPCs (p < 0.05) and higher plasma levels of VEGF (p < 0.05) than controls. Endothelial function was not different between OSA and controls. CONCLUSIONS: Patients with OSA free of any other known cardiovascular risk factor show a reduced number of circulating EPCs and an increase in plasma VEGF levels. These alterations may contribute to future endothelial dysfunction in these patients.

Circulating branched-chain amino acids in children with obstructive sleep apnea.

INTRODUCTION: The effects of obstructive sleep apnea (OSA) on the metabolic system are not well understood, especially in children. Recent studies have provided evidence of the modulation of insulin action by branched-chain amino acids (BCAAs) and suggested novel mechanistic relationships between glucose and amino acid metabolic pathways. We hypothesized that plasma BCAA levels may serve as biomarkers of insulin resistance and metabolic dysfunction in children with OSA. METHODS: A polysomnography was conducted for the diagnosis of OSA in 90 snoring children, in a tertiary hospital. Anthropometric and clinical data were measured and venous blood samples were collected for the measurement of plasma glucose, insulin, HbA1c, and amino acids. RESULTS: Children with OSA had significantly higher levels of BCAAs (leucine, isoleucine, and total BCAAs) compared with those without OSA (P = 0.024). A positive significant correlation was observed between insulin levels and both leucine and isoleucine (r = 0.232; P < 0.05). On multivariate regression analyses, the presence of OSA was significantly associated with leucine, isoleucine, and total BCAA concentrations (P = 0.028), whereas the arousal index was associated with leucine, valine, and total BCAA levels (P = 0.037). CONCLUSIONS: The presence of OSA and sleep fragmentation may induce changes in branched-chain amino acid metabolism in snoring children, independently of obesity. These data may suggest a new mechanism linking OSA and glucose homeostasis.