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PubMed2006

Advanced glycation endproducts in nondiabetic patients with obstructive sleep apnea.

SUBJECT OBJECTIVE: The formation and accumulation of advanced glycation endproducts (AGEs) has been implicated in the progression of age-related diseases such as diabetes mellitus and atherosclerosis. We hypothesize that AGE concentrations may be increased in subjects with obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: One hundred nineteen nondiabetic patients with OSA and 234 age-matched healthy controls and 134 patients with type 2 diabetes were recruited for participation in the study. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit antisera raised against AGE-RNase. RESULTS: Serum AGEs were increased in OSA subjects, as compared with controls, but were less increased than the AGEs of patients with type 2 diabetes (control: 3.22 +/- 0.54 unit per mL; OSA: 3.68 +/- 0.39; diabetes mellitus: 4.11 +/- 0.99; analysis of variance p < .01). In the subjects with OSA, serum AGEs correlated with the duration of nocturnal desaturation (r = 0.21, p = .025) and plasma total 8-isoprostane concentration, a biochemical marker of oxidative stress (r = 0.22, p = .015), but not with fasting glucose level. On general linear model univariate analysis, the association between serum AGEs and 8-isoprostane was independent of age, sex, body mass index, smoking status, and glucose. CONCLUSION: Serum levels of AGEs were increased in nondiabetic subjects with OSA and were associated with the severity of OSA. Whether increased AGE formation contributes significantly to the high cardiovascular risk associated with OSA remains to be determined.

Diabetes Mellitus, Type 2↗

PubMed2026

Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.

STUDY OBJECTIVES: To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (≥18 years) with severe OSA without insomnia. In each period, daridorexant 50 mg or placebo was administered every evening for 5 days. Primary and secondary endpoints were the treatment differences (daridorexant-placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI ≥10 events/h and mean decrease in nocturnal SpO2 ≤-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO). RESULTS: Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were -3.7 events/h (one-sided 95% CI ≤ +4.2) and - 0.12 % (one-sided 95% CI ≥ -0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5 min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3 min [90% CI: -20.6, -0.02]) and a trend towards reduced WASO (-15.2 min [-31.2, 0.9]). Four adverse events were reported (daridorexant n = 3; placebo n = 1), all of mild intensity and none related to respiratory function. CONCLUSION: Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193. Statement of Significance Obstructive sleep apnea (OSA) is highly prevalent and associated, in 30%-50% of cases, with insomnia-related symptoms, yet the safety of insomnia medications in OSA remains unclear. Daridorexant, a dual orexin receptor antagonist for the treatment of adults with insomnia disorder, previously showed no negative effect on sleep-disordered breathing in participants with mild/moderate OSA. This randomized, double-blind, placebo-controlled, crossover trial evaluates daridorexant 50 mg (maximum therapeutic dose) in participants with severe OSA without insomnia. Repeated dosing (5 nights) did not impair nighttime respiratory function, as assessed by apnea/hypopnea index and nocturnal oxygen saturation. Moreover, improvements in sleep characteristics were observed with daridorexant, extending evidence that daridorexant 50 mg is safe and well-tolerated and may improve sleep in adults with severe OSA.

Humans↗

PubMed1999

Ventilatory response to CO2 in children with obstructive sleep apnea from adenotonsillar hypertrophy.

UNLABELLED: We measured the ventilatory response to CO2 as an indicator of respiratory control dysfunction in children with obstructive sleep apnea (OSA) scheduled for adenotonsillectomy. Measurements were performed in unpremedicated children via an endotracheal tube under 0.4%-0.5% end-tidal halothane anesthesia. Mean ventilatory CO2 response slopes for 11 children with OSA requiring adenotonsillectomy (Group I) were compared with those for 14 children without OSA requiring adenotonsillectomy (Group II) and 15 children without OSA requiring nonairway surgery (Group III). The mean ventilatory slope corrected for body surface area for Groups I, II, and III were 539 +/- 338, 828 +/- 234, and 850 +/- 380 mL.min-1.mm Hg ETCO2(-1).m-2, respectively (P < 0.05, Group I versus Groups II and III). Historical data--including snoring, apneic episodes > 10 s, daytime hypersomnolence, and nocturnal enuresis--defined those with OSA. Obesity occurred more frequently in patients with OSA and with depressed ventilatory responses (P < 0.001). Children with OSA from adenotonsillar hypertrophy have a diminished ventilatory response to CO2 stimulation, compared with those without OSA symptoms. The depressed response may account, in part, for the reported increased risk of perioperative respiratory complications in this population. IMPLICATIONS: Children with obstructive sleep apnea undergoing adenotonsillar surgery are at risk of postoperative respiratory compromise. We found that patients with a clinical history suggesting obstructive sleep apnea have a diminished ventilatory response to CO2 rebreathing, compared with controls.

Adenoidectomy↗

PubMed1997

Floppy eyelid syndrome and obstructive sleep apnea.

Floppy eyelid syndrome (FES) usually affects middle-aged obese men, presenting as a unilateral or bilateral chronic papillary conjunctivitis. The upper eyelid is lax, floppy, and easily everted. The laterality corresponds to the side the patient sleeps on. An association with obstructive sleep apnea (OSA) has been suggested. A personal series of 17 new cases is presented, and 79 previously reported cases are reviewed to give a detailed description of the syndrome. In addition to the classical presentation, patients may present with upper lid ptosis, lash ptosis or trichiasis, lower lid ectropion or rarely entropion, or corneal complications. Eight patients with FES were investigated for OSA. Twenty other patients with known OSA were examined for FES and other possibly associated ocular features. All eight patients referred for sleep studies were found to have OSA. One of the 20 patients with known OSA was found to have FES, and two had features of early asymptomatic FES. One patient with FES and OSA had normal tension glaucoma. Patients with FES should be considered for sleep studies because of the known morbidity of OSA. Simple screening of patients with OSA may detect FES and avoid late corneal complications that can compromise vision.

Adolescent↗

PubMed2004

Clinical predictors in obstructive sleep apnea patients with computer-assisted quantitative videoendoscopic upper airway analysis.

AIM: To identify the clinical predictors and assist surgeons in their clinical management of obstructive sleep apnea (OSA). A prospective study with a new approach to analyze the static and dynamic upper airway morphology between patients with OSA and normal subjects. METHOD: Quantitative computer-assisted videoendoscopy (validated with upper airway magnetic resonance imaging) was performed in 49 (43 males, 6 females) patients with OSA and compared with 39 (22 males, 17 females) controls (apnea-hypopnea index [AHI] < 5). Absolute cross-sectional areas and transverse and longitudinal diameters at the retropalatal and retrolingual levels were measured during end of quiet respiration and during Mueller's maneuver in the erect and supine positions, allowing us to study static and dynamic morphology (collapsibility) of the upper airway. Three thousand seven hundred forty-four (3,744) parameters were analyzed. RESULTS: In males, retropalatal and retrolingual areas during Mueller's maneuver in the supine position of 0.7981 cm (relative operating characteristics [ROC] = 0.9284, positive pressure ventilation [PPV] = 86.05%, negative pressure ventilation [NPV] = 84.62%) and 2.0648 cm (ROC = 0.8183, PPV = 76%, NPV = 83.33%), respectively, were found to be good predictors/cut-off values for OSA. The retropalatal area measured in the supine position (AS1 mol/L) and collapsibility of the retropalatal area in the supine position (CAS1) were found to have significant correlations with severity of OSA. In females, the areas measured during Mueller's maneuver in the supine position of 0.522 cm at the retropalatal level (ROC = 1, 100% PPV and NPV) and the transverse diameter at the retrolingual level during erect Mueller's maneuver of 1.1843 cm (ROC = 0.9056, PPV = 100%, NPV = 83.33%) were found to be predictive. All measurements at the retropalatal level and in the supine position had higher predictability. Area measurements obtained during Muller's maneuver were more predictive (ROC > 0.9910) than resting measurements (ROC >0.8371). Several sex and anatomic-site specific formulas with excellent predictability (ROC close or equal to 1) were also devised. CONCLUSION: Upper airway Mueller's studies are predictive and useful (independent samples t test/Mann-Whitney U test, ROC) in identifying patients with OSA. With these sex and anatomic-site specific OSA predictors/formulas and this innovative clinical method, we hope to assist other surgeons with quantitative clinical diagnosis, assessment, surgical planning, and outcome assessment tools for OSA patients.

Cross-Sectional Studies↗

PubMed2006

Falls in blood pressure in patients with obstructive sleep apnoea after long-term nasal continuous positive airway pressure treatment.

OBJECTIVES: Effective treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long-term effects of nCPAP treatment on BP in OSA patients are not well known. The time period of such treatment sufficient to lower BP in OSA patients is also not known. We investigated compliance with long-term nCPAP therapy and its effects on BP. METHODS: This observational study involved 66 OSA patients [59 men, seven women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m; apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI were measured before the study and at two checkpoints after usage of nCPAP [620 (552-688) and 1071 (1000-1143) days]. RESULTS: The different times between the first and second checkpoints for detecting objective compliance were 17 (4-30) min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic BP and BMI did not change significantly. Usage of nCPAP treatment for a daily average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4 (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patients did not change significantly by nCPAP treatment, but that of hypertensive OSA patients decreased significantly within 1 month-3 years of nCPAP treatment whether or not medication was used. CONCLUSIONS: In patients with severe OSA, the use of nCPAP for a daily average of 3 h would be sufficient to decrease the diastolic BP of hypertensive OSA patients.

Blood Pressure↗

PubMed1994

Predictive value of specific risk factors, symptoms and signs, in diagnosing obstructive sleep apnoea and its severity.

A positive diagnosis of obstructive sleep apnoea (OSA) is based on a combination of characteristic symptoms and polysomnographic findings. The present study evaluated the specificity and sensitivity of several risk factors, signs and symptoms in predicting an Apnoea Index in 86 patients referred to the sleep laboratory with suspected OSA. All 86 subjects completed a detailed questionnaire, were interviewed, underwent a brief physical examination, and then a whole-night polysomnographic study. Stepwise multiple regression analysis revealed that self reporting on apnoeas, neck circumference index (NCI), age, and a tendency to fall asleep unintentionally, were all significant positive predictors of apnoea index (AI), explaining 41.8% of the variability. The sensitivity of the model for predicting OSA (taking OSA as AI > 10) was 92.2%, specificity was 18.2% and the positive predictive value was 76.6%. Raising the cut-off AI values resulted in decreased sensitivity and increased specificity. Applying the predicting equation of AI to another group of 50 patients referred to the sleep laboratory with suspected OSA revealed similar results. However, running the equation on 105 offspring of OSA patients who did not complain of OSA-associated symptoms resulted in 32% sensitivity and 94% specificity in predicting OSA. It is concluded that questionnaires, interviews and physical examination, can only vaguely predict AI, and cannot replace polysomnographic recordings. However, the low rates of false negative in predicting AI > 10, and the low rates of false positive in predicting AI > 50, can be used for specific purposes.

Journal Article↗

PubMed2005

Continuous positive airway pressure treatment improves the QT rate dependence adaptation of obstructive sleep apnea patients.

BACKGROUND: QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG. METHODS: The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder. RESULTS: QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime. CONCLUSIONS: The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.

Analysis of Variance↗

PubMed2005

First night effect for polysomnographic data in children and adolescents with suspected sleep disordered breathing.

AIMS: To assess the presence of a first night effect (FNE) in children and adolescents and to examine if a single night polysomnography (PSG) is sufficient for diagnosing obstructive sleep apnoea syndrome (OSAS). METHODS: Prospective case study of 70 patients (group 1: 2-6 years, n = 22; group 2: 7-12 years, n = 32; group 3: 13-17 years, n = 16) referred for OSAS. Diagnostic criteria for OSAS: one or more of the following: (1) obstructive apnoea index (OAI) > or =1; (2) obstructive apnoea hypopnoea index (oAHI) > or =2; (3) SaO2 < or =89% in association with obstruction. RESULTS: In all age groups, but mainly in the oldest children, REMS increased during the second night, mainly at the expense of stage 2 sleep. The first night PSG correctly identified OSAS in 86%, 91%, and 100% of the children for groups 1, 2, and 3 respectively. This represents 9% false negatives for OSAS when only the first night PSG was used. All cases missed had mild OSAS, except for one with oAHI >5 on night 2. There were also seven patients with OSAS on night 1 but with a normal PSG on night 2: all had oAHI <5. CONCLUSION: There is a FNE in children and adolescents. A single night PSG is sufficient for diagnosing OSAS, but in cases with a suggestive history and examination and with a negative first night, a second night study might be advisable.

Adolescent↗

PubMed2002

Use of tonsil size in the evaluation of obstructive sleep apnoea.

AIMS: (1) To determine the extent to which tonsil size contributes to the severity of obstructive sleep apnoea (OSA) in children; and (2) to assess the use of tonsillar-pharyngeal (TP) ratio in differentiating patients with different severity of OSA. METHODS: Lateral neck radiograph was performed on 35 children referred consecutively to a university paediatric chest clinic for suspected OSA secondary to tonsillar hypertrophy. The tonsil size was determined by measuring the TP ratio on the radiographs. The severity of OSA was assessed by overnight polysomnography. RESULTS: A total of 24 boys and 11 girls (median age 6.2 years) were studied. All presented with symptoms of OSA, and tonsillar hypertrophy was detected on clinical examination. The median apnoea-hypopnoea index (AHI) was 16.93 (interquartile range: 8.41 to 28.29). The median TP ratio was 0.76 (interquartile range: 0.65 to 0.80). AHI was positively correlated with the TP ratio. The clinical tonsil size did not correlate with the AHI or the TP ratio. Using a TP ratio of 0.479, the sensitivity and specificity in predicting cases with moderate/severe OSA (AHI >10) were 95.8% and 81.8% respectively, while the positive and negative predictive values were 92.0% and 90.0% respectively. CONCLUSIONS: Results show that in a population of children with OSA, tonsillar hypertrophy as assessed by lateral neck radiograph correlates positively with the severity of obstructive sleep apnoea. The TP ratio has high sensitivity and specificity in predicting those with moderate/severe disease and this feature may be used as a clinical screening method in prioritising patients with OSA for further assessment.

Child↗

PubMed2002

Cardiovascular medication use in patients with undiagnosed obstructive sleep apnoea.

BACKGROUND: A study was undertaken in patients with undiagnosed sleep apnoea/hypopnoea syndrome (OSAS) to document the use of prescribed medications, especially those used in cardiovascular diseases, in the year before the OSAS diagnosis was confirmed. METHODS: A total of 549 patients with OSAS (401 men of mean age 47.2 years, mean body mass index (BMI) 35.5 kg/m(2), mean apnoea/hypopnoea index (AHI) 47.2 and148 women of mean age 50.2 years, BMI 39.6 kg/m(2), AHI 32.6) were each matched to one general population control by age, sex, geographical location, and family physician. Medication use was evaluated for patients and controls using a database containing information about all prescriptions completed in the province of Manitoba, Canada. RESULTS: In the year before OSAS was diagnosed, prescribed medication costs were $155.91 (Canadian dollars) (95% CI $91.34 to $220.49) greater for cases than for controls. Cases were dispensed 3.3 (95% CI 1.5 to 5.2) more prescriptions, were on 1.2 (95% CI 0.8 to 1.6) more medications, and were supplied with 157.4 (95% CI 95.9 to 218.8) more daily doses of medication. The odds ratio of OSAS cases being on a prescribed medication was 1.88 relative to controls (95% CI 1.38 to 2.54, p<0.0001). In the same year 36.6% of cases and 19.7% of controls were using medications for cardiovascular disease (OR 2.82, 95% CI 2.05 to 3.89, p<0.0001), consuming 79.4 (95% CI 48.9 to 109.8) more daily doses of medication, having been dispensed 1.7 (95% CI 1.0 to 2.4) more prescriptions, and at a $75.26 (95% CI $44.03 to $106.50) greater cost. The odds ratio of patients with OSAS being on medications indicated for the treatment of systemic hypertension was 2.71 (95% CI 1.96 to 3.77) relative to controls; however, such medications might also be prescribed for other indications such as angina pectoris and congestive heart failure, and for the secondary prevention of myocardial infarction. The use of medications indicated for the treatment of systemic hypertension was predicted significantly by age (odds ratio (OR) 1.10 per year), BMI (OR 1.05 per unit), and AHI (OR 1.01 per unit). CONCLUSIONS: In the year before OSAS was diagnosed, patients with OSAS were heavy users of medications, particularly those used to treat cardiovascular diseases.

Body Mass Index↗

PubMed1998

Arousal and ventilatory responses during sleep in children with obstructive sleep apnea.

Abnormal central regulation of upper airway muscles may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). We hypothesized that this was secondary to global abnormalities of ventilatory control during sleep. We therefore compared the response to chemical stimuli during sleep between prepubertal children with OSAS and controls. Patients with OSAS aroused at a higher PCO2 (58 +/- 2 vs. 60 +/- 5 Torr, P < 0.05); those with the highest apnea index had the highest arousal threshold (r = 0.52, P < 0.05). The hypercapnic arousal threshold decreased after treatment. For all subjects, hypoxia was a poor stimulus to arousal, whereas hypercapnia and, particularly, hypoxic hypercapnia were potent stimuli to arousal. Hypercapnia resulted in decreased airway obstruction in OSAS. Ventilatory responses were similar between patients with OSAS and controls; however, the sample size was small. We conclude that children with OSAS have slightly blunted arousal responses to hypercapnia. However, the overall ventilatory and arousal responses are normal in children with OSAS, indicating that a global deficit in respiratory drive is not a major factor in the etiology of childhood OSAS. Nevertheless, subtle abnormalities in ventilatory control may exist.

Arousal↗

PubMed2002

In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome.

BACKGROUND: Patients with obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular events including myocardial infarction and stroke. OBJECTIVE: To determine whether in vivo platelet activation and the generation of procoagulant platelet-derived microparticles (PMP) are increased during sleep in patients with OSAS. METHODS: In vivo platelet activation and PMP formation was determined using flow cytometry in 12 patients with untreated OSAS during and after sleep (4 and 7 a.m.). To study the effect of treatment with continuous positive airway pressure (CPAP), the measurements were repeated at the same time points after initiation of CPAP therapy. Healthy volunteers served as controls (n = 6). RESULTS: Patients with OSAS had an increased percentage of platelets positive for the activation-dependent epitopes CD63 and CD62P during sleep (4 a.m.) compared to controls (4.8 +/- 0.8 vs. 1.9 +/- 0.4% for CD63, p < 0.01, and 2.0 +/- 0.5 vs. 1.1 +/- 0.3% for CD62P, p < 0.05). In OSAS patients, the amount of CD63- and CD62P-positive platelets was significantly elevated at 4 compared to 7 a.m. (4.8 +/- 0.8 vs. 2.6 +/- 0.4% for CD63 and 2.0 +/- 0.5 vs. 1.1 +/- 0.2% for CD62P, p < 0.05), but not in the control group. The levels of PMP were similar in patients with OSAS and controls at 4 and 7 a.m. After 1 night of CPAP therapy, there was a trend to reduced levels of CD63- and CD62P-positive platelets at 4 a.m. CONCLUSIONS: Patients with OSAS have increased in vivo platelet activation during sleep, which may contribute to the increased incidence of cardiovascular events in patients with OSAS.

Aged↗

PubMedDate not supplied

Increased prevalence of perennial allergic rhinitis in patients with obstructive sleep apnea.

BACKGROUND: Impaired nasal breathing is a risk factor for obstructive sleep apnea syndrome (OSAS). OBJECTIVES: The aim of this study was to determine whether atopy to perennial allergens and existence of perennial allergic rhinitis was a risk factor for OSAS. METHODS: In a case-control study, we compared the proportions of OSAS patients with atopy to perennial allergens and perennial allergic rhinitis to the proportions in patients with chronic obstructive pulmonary disease (COPD). Seventy-two OSAS patients (mean age 60.7 years; 79.4% male) and 44 COPD patients (mean age 63.6 years; 88.6% male) were selected from a hospital outpatients' clinic in Switzerland. All patients completed a respiratory symptom questionnaire, performed spirometry and had a skin prick test for atopy. RESULTS: OSAS patients were significantly heavier than COPD patients (BMI 32.4 +/- (SD) 6.6 vs. 29.2 +/- 6.6 kg/m2, p = 0.04) and had a better lung function than COPD patients (FEV1% predicted 91.3 +/- 19.2 vs. 51.6 +/- 18.9%, p < 0.001). Patients with OSAS were more likely to be sensitized to perennial allergens such as house dust mite (23.6 vs. 4.5%, p = 0.009) and dog (18 vs. 4.5%, p = 0.04) than the COPD patients. Perennial allergic rhinitis (having nose problems [nasal obstruction and/or runny nose and/or sneezing] all year and being atopic to at least one perennial allergen) was reported in 11% of OSAS patients but in only 2.3% of COPD patients (p = 0.15). CONCLUSION: We conclude that subjects with OSAS may have an increased risk of being allergic to perennial allergens and suffer from perennial rhinitis. Awareness of this risk may have important consideration in the clinical situation.

Administration, Intranasal↗

PubMedDate not supplied

Impact of obstructive sleep apnea on right ventricular global function: sleep apnea and myocardial performance index.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstructions during sleep, and it might cause cardiovascular complications such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary hypertension. OBJECTIVES: To determine right ventricular diameters and myocardial performance index (MPI) reflecting ventricular global function in uncomplicated OSA patients. METHODS: 49 subjects without hypertension, diabetes mellitus, or any cardiac or pulmonary disease referred for evaluation of OSA had overnight polysomnography and complete echocardiographic assessment. According to the apnea-hypopnea index (AHI), subjects were divided into three groups: group 1: control subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5-14, n = 11), and group 3: moderate-severe OSA (AHI > or = 15, n = 18). Right ventricular free wall diameter was measured by M mode, and right ventricular MPI was calculated as (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection time. RESULTS: There were no differences of age, body mass index, heart rates, systolic and diastolic blood pressures among the groups (p > 0.05). Right ventricular end-diastolic and end-systolic diameters were not statistically different between the groups, and were within normal limits. Also, right ventricular free wall diameter was not significantly different between the groups of control, mild OSA and moderate-severe OSA (6.7 +/- 0.9, 6.9 +/- 1.0, 7.1 +/- 1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62 +/- 0.18) than in group 2 patients (0.50 +/- 0.10), and group 1 patients (0.48 +/- 0.08, p < 0.001). CONCLUSIONS: It was suggested that patients with moderate-severe OSA had a right ventricular global dysfunction, in addition to the presence of a diastolic dysfunction.

Adult↗

PubMed2006

Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.

Aorta, Thoracic↗

PubMed2006

Association of elevated levels of vascular endothelial growth factor in obstructive sleep apnea syndrome with patient age rather than with obstructive sleep apnea syndrome severity.

BACKGROUND: Although certain studies report high levels of vascular endothelial growth factor (VEGF) in obstructive sleep apnea syndrome (OSAS), the effect of systemic hypoxia on circulating VEGF remains controversial. OBJECTIVES: To study the association of serum VEGF and OSAS in a large group of patients. METHODS: One hundred patients with OSAS (mean age 58.1+/-12.4 years, mean body mass index 30.6+/-5.4 kg/m2) were tested for serum VEGF levels, and the findings were correlated with the severity of OSAS, as determined by the apnea-hypopnea index (AHI) on the basis of polysomnography and background data. RESULTS: The mean AHI was 40.0+/-21.2 (range 10-106). Mean minimal oxygen saturation was 80.6+/-11.7% (range 43-98%) and mean time of oxygen saturation under 90% was 50.0+/-75.0 min (range 0-300 min). The mean VEGF level was 445.2+/-289.8 pg/ml in the study group (vs. 280 pg/ml reported in normal controls). The mean platelet count was 233.8+/-64.4 10(3)/ml and the mean VEGF/platelet ratio was 1.95+/-1.40 pg/10(6). There was no association of VEGF or VEGF/platelets with the severity of OSAS. However, both factors showed a significant correlation with patient age (r=0.224, p=0.01 and r=0.425, p=0.01, respectively). Age was the only parameter to significantly predict VEGF and VEGF/platelets on multivariate analysis (R2=0.713, p=0.001 and R2=0.844, p=0.001, respectively). CONCLUSION: The elevation of serum VEGF in OSAS is not associated with the severity of the disease, but it is associated with patient age. VEGF might be involved in the long-term adaptive mechanism in OSAS, and its age-dependent increase might partly explain the reduced mortality in elderly OSAS patients.

Adult↗

PubMed2006

Circulating ICAM-1 and VCAM-1 levels in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS)-induced hypoxic stress modulates circulating inflammatory mediators causing accelerated atherogenesis. OBJECTIVES: We hypothesized that OSAS-induced hypoxia might result in cardiovascular disease due to increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial surface. METHODS: Thirty-nine subjects with moderate-to-severe OSAS and 34 non-apneic controls matched for age, gender, body mass index (BMI), smoking history, and cardiovascular disease were included in this prospective study. Overnight polysomnography was performed. Circulating ICAM-1 and VCAM-1 levels in the serum were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating levels of both ICAM-1 (480.1 +/- 216.7 vs. 303.4 +/- 98.6 ng/ml, p < 0.0001) and VCAM-1 (1,156.6 +/- 79.8 vs. 878.8 +/- 71.1 ng/ml, p = 0.002) were significantly increased in the OSAS group compared to the control group. For an ICAM-1 cutoff level of 375 ng/ml, predictive sensitivity and specificity for OSAS were 69.2% (95% confidence interval, CI: 52.4-83.0%) and 82.4% (95% CI: 65.5-93.2%), respectively. For a VCAM-1 cutoff level of 859 ng/ml, predictive sensitivity and specificity for OSAS were 74.4% (95% CI: 57.9-86.9%) and 64.7% (95% CI: 46.5-80.2%), respectively. There was a significant positive correlation between circulating levels of ICAM-1 and ln of AHI (r = 0.276, p = 0.018). Multiple logistic regression analyses showed that OSAS was associated with high ICAM-1 and high VCAM-1 levels independent of age, gender, BMI, smoking status and cardiovascular disease. CONCLUSION: We conclude that OSAS can independently increase circulating levels of adhesion molecules

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