[Show abstract][Hide abstract] ABSTRACT: The main purpose of the present analysis is to assess the influence of introducing early nasal continuous positive airway pressure (nCPAP) treatment on cardiovascular recurrences and mortality in patients with a first-ever ischaemic stroke and moderate-severe obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥20 events h(-1) during a 5-year follow-up. Patients received conventional treatment for stroke and were assigned randomly to the nCPAP group (n = 71) or the control group (n = 69). Cardiovascular events and mortality were registered for all patients. Survival and cardiovascular event-free survival analysis were performed after 5-year follow-up using the Kaplan-Meier test. Patients in the nCPAP group had significantly higher cardiovascular survival than the control group (100 versus 89.9%, log-rank test 5.887; P = 0.015) However, and also despite a positive tendency, there were no significant differences in the cardiovascular event-free survival at 68 months between the nCPAP and control groups (89.5 versus 75.4%, log-rank test 3.565; P = 0.059). Early nCPAP therapy has a positive effect on long-term survival in ischaemic stroke patients and moderate-severe OSA.
Journal of Sleep Research 07/2014; · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is associated with an increased prevalence of cardiovascular diseases. New generations of highly sensitive assays for cardiac troponin (hs-cTnT) have been introduced recently, and a number of clinical observations have challenged the notion that troponins are only increased in blood following irreversible necrosis.
The aims of this study were to compare the levels of hs-cTnT between a group of healthy controls and a group of patients with OSA without co-existent coronary artery disease, and to assess the possible influence of the treatment with Continuous positive airway pressure (CPAP) on these levels.
The study population included 200 male participants. The case (n = 133) or control (n = 67) status was defined by an apnea-hypopnea index of 10 or greater. The hs-cTnT assay was validated as reported previously, with a limit of detection of 3 ng/L and an upper reference limit (99th percentile) of 14 ng/L.
The proportion of subjects with detectable plasma hs-cTnT was higher in patients with OSA than in controls (61 vs 75%, p = 0.04). In patients, a significant increase in hs-cTnT levels was observed after an effective treatment with CPAP (7.3 ± 3.4 vs 10.1 ± 4.9 ng/L; p < 0.01).
This study shows that the percentage of subjects with detectable hs-cTnT is associated with the presence of OSA. It also evidences that treatment with CPAP is followed by a rise in hs-cTnT concentrations. It is reasonable to suggest that CPAP therapy might induce a potential degree of cardiac stress, resulting in deleterious consequences for the heart.
Respiratory medicine 04/2014; · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Critical CareSESSION TYPE: Slide PresentationPRESENTED ON: Saturday, March 22, 2014 at 04:15 PM - 05:15 PMPURPOSE: Non invasive ventilation (NIV) is a standardized treatment that has proven beneficial effects in different respiratory and cardiologic diseases. The increasing development of NIV has enabled chest physicians to assist more complex patients and stimulate the setting-up of specials units (Respiratory High-Dependency Care Units [RHDCU]). These units are specialized in severe respiratory patients who need NIV and monitoring. The aim of this study was to evaluate the impact of a RHDCU in non-invasive ventilated patients.
Prospective study that compared the role of a RHDCU dependent on a Pneumology department with respect to a conventional ward, in NIV patients admitted in Hospital Son Espases between July 2011 and June 2012. Cardiac failure patients and domiciliary NIV were excluded.
88 patients were included, 46 admitted in RHDCU and 42 in conventional ward. The patients admitted in RHDCU, with respect to ward patients showed, respectively, worse pulmonary function (FEV1 post-bd. 37±15% pred. vs. 52±27% pred), higher severity index (APACHE: 21±6 vs. 13±5) and lower hospital stays (12±7 vs. 17±13 days) (p<0.05). Furthermore, the patients admitted to the RHDCU had a lower pH (7.25 ±0.07 vs. 7.28±0.06) and less NIV duration (5.4±3.4 vs 6.5±7.3 days) compared with the patients in conventional wards, with no statistical significance. However, we found no differences in mortality and readmissions between both groups.
A RHDCU dependent on a Pneumology department allows the physician: 1) to apply NIV in more severe patients; 2) to decrease the hospital stay in patients treated with NIV; and, 3) all, with no increase in mortality or readmissions.
Respiratory High-Dependency Care Units dependent on a Pneumology department afford the possibility to treat more severe patients with a higher level of monitoring and allow to identify therapeutic failures prematurely.
The following authors have nothing to disclose: Alejandro Peralta, Lucia Gimeno, Cristina Oliver, Alicia Binimelis, Belen Nuñez, Miguel Carrera, Monica de la Peña, Ernest SalaNo Product/Research Disclosure Information.
[Show abstract][Hide abstract] ABSTRACT: OSA PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: Home single-channel nasal pressure (HNP) may be an alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis but no cost studies have been carried out. Automatic scoring is simpler but generally less effective than manual scoring. Objectives: To determine the diagnostic efficacy and cost of both scorings (automatic and manual) compared with PSG, taking as a polysomnographic OSA diagnosis a clinical-epidemiological apnea-hypopnea index (AHI) cut-off point (≥5) and a clinical-therapeutic AHI cut-off point (≥15).
We included suspected OSA patients in a multicenter study. They were randomized to home and hospital protocols. We constructed Receiver Operating Characteristic (ROC) curves for both scorings. Diagnostic efficacy was explored for several HNP AHI cut-off points and costs were calculated for equally effective alternatives.
Of 787 randomized patients, 752 underwent HNP. Manual scoring produced better ROC curves than automatic for AHI≥5 and similar for AHI≥15. A valid HNP would correctly classify the OSA presence (or otherwise) with manual scoring for a clinical-epidemiological diagnosis in 90% of patients and with automatic scoring for a clinical-therapeutic diagnosis in 60%. The costs of either HNP approach were 40%-70% lower than those of PSG. Manual HNP for clinical-epidemiological diagnosis had the lowest cost and manual and automatic scorings had similar costs for clinical-therapeutic diagnosis.
HNP is a cheaper alternative than PSG for OSA diagnosis. Manual HNP scoring seems especially useful for epidemiological studies on a clinical population base, although manual or automatic scorings can achieve a suitable diagnosis for clinical-therapeutic management
The use of a very simple automatic device favor the use for non-specialist practitioners for the management of patients with sleep apnea suspicion
The following authors have nothing to disclose: Juan F. Masa, Joaquín Durán-Cantolla, Francisco Capote, Marta Cabello, Jorge Abad, Francisco Garcia-Rio, Antoni Ferrer, Merche Mayos, Nicolás Mangado, Mónica de la Peña, Felipe Aizpuru, Ferran Barbé, Jose M. MontserratNo Product/Research Disclosure Information.
[Show abstract][Hide abstract] ABSTRACT: Metabolic syndrome (MS) occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS.
We studied 66 patients with OSAHS (33 with MS and 33 without MS) and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) clinical criteria. Measurements of plasma renin activity (PRA), aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment.
Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046). Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041). A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012).
This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS.
The study is not a randomized controlled trial and was not registered.
PLoS ONE 01/2014; 9(1):e84362. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Obstructive sleep apnea (OSA) has been associated with metabolic disorders. Sleep-disordered breathing could generate an altered rhythm in the expression of metabolic hormones, which could predispose to metabolic disorders. The aim of this study was to evaluate the effect of sleep apnea on diurnal variations in metabolic hormones.
Thirty-seven male, newly diagnosed, patients with OSA with an apnea–hypopnea index (AHI) ⩾20/h and 11 male controls (AHI <10/h) matched for body mass index (±3 kg/m2) were included. Six different samples were obtained from each subject during a period of 24 h. Levels of the metabolic hormones ghrelin, leptin, resistin, and adiponectin were measured in plasma by immunoassay.
Patients with OSA (AHI (mean ± SD) 46 ± 26/h) were older than the controls (42 ± 9 vs 33 ± 9 years, P = 0.01). Differences in metabolic hormones between groups did not reach statistical significance at any point in the evaluation. No significant differences were observed in the area under the curve for any of the hormones analysed. Likewise, we did not detect diurnal variations in metabolic hormones.
The results of this study indicate that the day–night variations in the levels of several metabolic hormones are not influenced by the presence of sleep apnea.
[Show abstract][Hide abstract] ABSTRACT: Objective
The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion.
This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea–hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox’s proportional regression analyses after adjusting for relevant confounders.
In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02–1.41). The closest association was shown in patients <65 years in both the AHI (continuous log-transformed AHI, HR, 1.87; 95% CI, 1.1–3.2; upper vs lower AHI tertile, HR, 3.98; 95% CI, 1.14–3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23–2.4; upper vs lower TSat90 tertile: HR, 14.4; 95% CI, 1.85–111.6).
OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.
[Show abstract][Hide abstract] ABSTRACT: More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) treatment on blood pressure in patients with resistant hypertension.
To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA.
Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011.
CPAP or no therapy while maintaining usual blood pressure control medication.
The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed.
A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg [95% CI, 0.6 to 5.6]; P = .02) and 24-hour DBP (3.2 mm Hg [95% CI, 1.0 to 5.4]; P = .005), but not in 24-hour SBP (3.1 mm Hg [95% CI, -0.6 to 6.7]; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio [OR], 2.4 [95% CI, 1.2 to 5.1]; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005).
Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes.
clinicaltrials.gov Identifier: NCT00616265.
JAMA The Journal of the American Medical Association 12/2013; 310(22):2407-15. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To compare the prevalence of obstructive sleep apnea (OSA) in patients with pulmonary embolism (PE) with a sex-, age-, and body mass index (BMI)-matched, population-based control group and to assess the association between OSA and PE. METHODS: We performed a case-control study from October 1, 2006, through November 30, 2009. We included 107 patients with PE and a control group (n=102) without PE in University Hospitals Son Espases and La Paz in Spain. Variables included in the analysis were medical history, anthropometric variables (weight, height, BMI, and neck circumference), Epworth Sleepiness Scale score, home respiratory polygraphy, basic biochemical profile and hemogram, spirometry, and physical activity. RESULTS: The mean ± SD apnea-hypopnea index (AHI) was significantly higher in patients with PE than population controls (21.2±20.6 vs 11.5±15.9 h(-1); P<.001). The presence of an AHI greater than 5 h(-1) and hypersomnolence (Epworth Sleepiness Scale score ≥11) was more frequent in PE patients than in controls (14.0% vs 4.9%; P=.0002). A crude model analysis by several cutoffs revealed that the AHI was significantly associated with PE. After adjustment for age, sex, smoking, BMI, lung function, and all known PE risk factors, the odds ratio for PE was 3.7 (95% CI, 1.3-10.5; P=.01). CONCLUSION: A higher prevalence of OSA was detected in patients diagnosed as having acute PE than controls. This study identified a significant and independent association between OSA and PE.
Mayo Clinic Proceedings 04/2013; · 5.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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, p(trend) = 0.038] and MS (OR 0.34, 95% CI 0.21-0.56, p(trend) < 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, p(trend )< 0.001) and hypertension (OR 1.83, 95% CI 1.01-3.05, p(trend )= 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.
[Show abstract][Hide abstract] ABSTRACT: RATIONALE: Obstructive Sleep Apnea (OSA) has been associated with increased cancer mortality, but whether it is also associated with cancer incidence is unknown. OBJECTIVE: To investigate whether OSA is associated with increased cancer incidence in a large clinical cohort. METHODS: Multicenter, clinical cohort study including consecutive patients investigated for suspected OSA between 2003-2007 in 7 Spanish teaching hospitals. Apnea-hypopnea index (AHI) and percent night-time with oxygen saturation <90% (TSat90) were used as surrogates of OSA severity, both as continuous variables and categorized by tertiles. Cox proportional hazards regression analyses were used to calculate hazard ratios (HR) and 95%CI for cancer incidence after adjusting for confounding variables. MEASUREMENTS AND MAIN RESULTS: 4,910 patients were analyzed (median follow-up 4.5 years, IQR 3.4-5.2). Compared to the lower TSat90 category (<1.2%), the adjusted hazards (95%CI) of cancer incidence for increasing categories were 1.58 (1.07-2.34) for TSat90 1.2%-12% and 2.33 (1.57-3.46) for TSat90>12%. Continuous TSat90 was also associated with cancer incidence (adjusted HR 1.07 [1.02-1.13] per 10-unit increase in TSat90). In stratified analyses, TSat90 was associated with cancer incidence in patients <65 years (adjusted HR 1.13 [95%CI 1.06-1.21] per 10-unit increase in TSat90) and males (adjusted HR 1.11 [95%CI 1.04-1.17] per 10-unit increase in TSat90). AHI was not associated with cancer incidence in the adjusted analyses, except for patients <65 years (adjusted HR for AHI>43 vs. <18.7: 1.66, 95%CI 1.04-2.64). CONCLUSIONS: Increased overnight hypoxia as a surrogate of obstructive sleep apnea severity was associated with increased cancer incidence. This association seems to be limited to men and patients <65 years.
American Journal of Respiratory and Critical Care Medicine 11/2012; · 11.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear.
To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA.
Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009.
Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice.
Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).
Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20).
In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference.
clinicaltrials.gov Identifier: NCT00127348.
JAMA The Journal of the American Medical Association 05/2012; 307(20):2161-8. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Sleep And Breathing 09/2011; 16(3):649-56. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
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.
Sleep And Breathing 09/2011; 15(3):403-8. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnea (OSA) is related to obesity and metabolic disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and snoring. However, not all patients with OSA manifest EDS. Hypocretin-1, neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic and sleep regulation, two conditions affected by OSA. We hypothesized that levels of these peptides may be related to EDS in OSA patients.
We included 132 patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score ≥ 13 (mean ± SD, 15.7 ± 2.3) and 132 patients without EDS as defined by an ESS score ≤ 9 (6.5 ± 1.9). All patients had an apnea-hypopnea index (AHI) ≥ 20 h(-1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 ± 11.2 yrs vs. 50.7 ± 9.9 yrs), body mass index (BMI) (31.8 ± 5.6 kg m(-2) vs. 32.1 ± 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 ± 19.1 h(-1) vs. 43 ± 19.2 h(-1)).
OSA patients with EDS showed significantly higher plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p < 0.001) than OSA patients without EDS. There were no statistically significant differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p = 0.72) between the two groups. In the multiple linear regression model ESS score was associated with plasma levels of hypocretin-1, ghrelin and total sleep time.
Our study shows that EDS in patients with OSA is associated with increased circulating hypocretin-1 and decreased circulating ghrelin levels, two peptides involved in the regulation of body weight, energy balance, sympathetic tone and sleep-wake cycle. This relationship is independent of AHI and obesity (two key phenotypic features of OSA).
Respiratory medicine 09/2011; 105(12):1954-60. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with sleep apnoea have a significant alteration in the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population. The aim of this study was to investigate the influence of sleep apnoea on the diurnal variations in various haemostatic parameters (factor VII, von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40 ligand (sCD40L)). We studied 26 male patients with obstructive sleep apnoea syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30 events · h(-1)) and 13 patients with mild-to-moderate OSAS (AHI <30 events · h(-1))) and 12 controls of similar body mass index (BMI) and waist circumference. In each subject, six different samples were obtained over 24 h. Although all the markers values tended to be higher in patients with severe OSAS, differences did not reach statistical significance at any time. PAI-1 levels were significantly related to BMI (p<0.001), mean (p<0.001) and minimal (p = 0.047) nocturnal oxygenation saturation. ADMA levels were significantly related to arousal index (p = 0.046). The results of this study suggest that day-night variations in factor VII:antigen (Ag), von Willebrand factor:Ag, PAI-1, sCD40L and ADMA levels may be dependent on either the obesity index or metabolic dysfunction rather than on sleep apnoea alone.
European Respiratory Journal 08/2011; 39(4):913-8. · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system.
Endocrinología y Nutrición 06/2011; 58(6):299-307.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess the impact of nasal continuous positive airway pressure (nCPAP) in ischaemic stroke patients followed for 2 yrs. Stroke patients with an apnoea-hypopnoea index ≥ 20 events·h⁻¹ were randomised to early nCPAP (n = 71; 3-6 days after stroke onset) or conventional treatment (n = 69). The Barthel Index, Canadian Scale, Rankin Scale and Short Form-36 were measured at baseline, and at 1, 3, 12 and 24 months. The percentage of patients with neurological improvement 1 month after stroke was significantly higher in the nCPAP group (Rankin scale 90.9 versus 56.3% (p < 0.01); Canadian scale 88.2 versus 72.7% (p < 0.05)). The mean time until the appearance of cardiovascular events was longer in the nCPAP group (14.9 versus 7.9 months; p = 0.044), although cardiovascular event-free survival after 24 months was similar in both groups. The cardiovascular mortality rate was 0% in the nCPAP group and 4.3% in the control group (p = 0.161). Early use of nCPAP seems to accelerate neurological recovery and to delay the appearance of cardiovascular events, although an improvement in patients' survival or quality of life was not shown.
European Respiratory Journal 05/2011; 37(5):1128-36. · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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.
Sleep And Breathing 03/2011; 16(2):355-60. · 2.26 Impact Factor