Camila F. Rizzi

Cysteine A Potential Biomarker for Obstructive Sleep Apnea

OBJECTIVE Obstructive sleep apnea (OSA) is a risk factor for a number of cardiovascular conditions. Although homocysteine (Hcy) and cysteine (Cys) are regarded as cardiovascular risk factors, few studies have analyzed Hcy and Cys plasma concentrations in patients with OSA. The aim of this study was to evaluate the role of Hcy and Cys in OSA in comparison with subjects without OSA and to determine the possible influence of obesity on these variables. METHODS Patients who submitted to polysomnography studies were recruited to engage in an 8-h fasting period for blood sample withdrawal, physical examination, ECG, and echocardiogram. A subgroup of lean patients with OSA (BMI < 25 kg/m(2)) were analyzed to rule out the influence of obesity. Fifteen patients were randomly assigned to participate in a continuous positive airway pressure (CPAP) protocol to assess the influence of OSA treatment on the obtained measurements. RESULTS A total of 75 patients and 75 control subjects matched for age and sex were analyzed. The Cys plasma levels were higher in patients with OSA compared with control subjects (490.16 ± 67.00 μmol/L vs 439.81 ± 76.12 μmol/L, respectively, P < .01); however, the Hcy plasma levels did not differ between groups. Cys plasma levels were also higher in the OSA lean subgroup when compared with lean control subjects (484.21 ± 71.99 μmol/L vs 412.01 ± 70.73 μmol/L, respectively, P = .009). There was a significant decrease of Cys plasma levels after 6 months of CPAP effective therapy. CONCLUSION Cys is a potential biomarker of OSA in obese and nonobese patients and is reduced after effective OSA treatment.

Exercise Capacity and Obstructive Sleep Apnea in Lean Subjects

BACKGROUND Conflicting data regarding exercise capacity and obstructive sleep apnea (OSA) have been published, which may be partially explained by the difficulty of controlling all of the confounding factors. The aim of this study is to evaluate the exercise, anthropometric, and blood parameters in lean, sedentary patients with OSA compared with controls. METHODS Fifty-four lean subjects (including 27 patients with OSA and 27 controls) were selected. The control group was matched for age and gender. All subjects underwent polysomnography, anthropometric measures, a cardiorespiratory exercise test, two-dimensional transthoracic echocardiography, and spirometry. RESULTS The mean age was 52.9 +/- 7.9 years in subjects with OSA and 52.8 +/- 8.1 years in controls (P = .95). The cervical circumference was greater in the lean OSA group when compared with the controls (33.7 +/- 3.5 cm vs 31.4 +/- 2.8 cm; P = .01). There were statistical differences in the apnea-hypopnea index, minimal oxygen saturation, and mean oxygen saturation in the lean patients with OSA. Glycemia was higher in the lean OSA group (115.1 +/- 50.1 mg/dL vs 94.2 +/- 9.8 mg/dL; P = .04). There were no differences between groups in the peak oxygen consumption (Vo(2)), anaerobic threshold (AT), respiratory exchange ratio (RER), BP, and heart rate. CONCLUSION High glycemia and cervical circumference enlargement are the main characteristics of lean patients with OSA. Exercise performance is similar between groups, considering the peak Vo(2), AT, and RER. These results suggest that OSA does not impair functional capacity in lean subjects and that obesity probably participates in the diminished cardiopulmonary capacity observed in patients with OSA.

Does Obstructive Sleep Apnea Impair the Cardiopulmonary Response to Exercise

STUDY OBJECTIVES The aim of this study was to evaluate cardiopulmonary exercise performance in lean and obese patients with obstructive sleep apnea (OSA) compared with controls. DESIGN Case-control study. SETTING The study was carried out in Sao Paulo Sleep Institute, Sao Paulo, Brazil. PATIENTS AND PARTICIPANTS INDIVIDUALS WITH SIMILAR AGES WERE ALLOCATED INTO GROUPS: 22 to the lean OSA group, 36 to the lean control group, 31 to the obese OSA group, and 26 to the obese control group. INTERVENTIONS The participants underwent a clinical evaluation, polysomnography, a maximum limited symptom cardiopulmonary exercise test, two-dimensional transthoracic echocardiography, and spirometry. MEASUREMENTS AND RESULTS The apnea-hypopnea index, arousal index, lowest arterial oxygen saturation (SaO2) and time of SaO2 < 90% were different among the groups. There were differences in functional capacity based on the following variables: maximal oxygen uptake (VO2max), P < 0.01 and maximal carbon dioxide production (VCO2max), P < 0.01. The obese patients with OSA and obese controls presented significantly lower VO2max and VCO2max values. However, the respiratory exchange ratio (RER) and anaerobic threshold (AT) did not differ between groups. Peak diastolic blood pressure (BP) was higher among the obese patients with OSA but was not accompanied by changes in peak systolic BP and heart rate (HR). When multiple regression was performed, body mass index (P < 0.001) and male sex in conjunction with diabetes (P < 0.001) independently predicted VO2max (mL/kg/min). CONCLUSIONS The results of this study suggest that obesity alone and sex, when associated with diabetes but not OSA, influenced exercise cardiorespiratory function.

Quality-adjusted life-years gain and health status in patients with OSAS after one year of continuous positive airway pressure use.

STUDY OBJECTIVES To estimate the health utility score and quality-adjusted life-years (QALY) index of obstructive sleep apnea syndrome (OSAS) in patients over 1 y of continuous positive airway pressure (CPAP) treatment. DESIGN Longitudinal interventional study. SETTING The study was carried out in Sao Paulo Sleep Institute, Brazil. PATIENTS AND PARTICIPANTS Ninety-five patients with OSAS and with apnea-hypopnea index (AHI) > 20 of either sex, body mass index < 40 kg/m(2), and no previous contact with CPAP were included. INTERVENTIONS The participants underwent baseline and titration polysomnographies, clinical evaluation, and ambulatory blood pressure (BP) measurement, completed Short-Form 6 Dimension Health Survey (SF-6D) and Epworth Sleepiness Scale (ESS) questionnaires, and implementation of CPAP. The patients were followed for 1 y. MEASUREMENTS AND RESULTS The mean AHI and age were 57.6 ± 29.2 events/h and 53.3 ± 9.3 y, respectively. One year of CPAP treatment increased the health utility score from 0.611 ± 0.112 to 0.710 ± 0.121 (P < 0.01). Therefore, CPAP resulted in a mean gain of 0.092 QALY/patient. The improvements in utility scores were associated with decreases in the ESS after 1 mo, in systolic BP after 1 y, and in diastolic BP at 6 mo. BP normalization group (≤ 130/85 mmHg) showed higher QALY than that of the non-normalization group (0.10 ± 0.09 versus 0.05 ± 0.10; P = 0.03). One-year ESS score (P = 0.03), diastolic BP reduction P = 0.01) and baseline utility scores (P < 0.01) were significantly associated with QALY gain. CONCLUSION This study showed a significant QALY/patient gain after 1 y of regular CPAP use. In addition, BP normalization was associated with higher QALY gain. Thus, utility studies can provide more complete analyses of the total benefits of CPAP treatment in patients with OSAS and should be encouraged.

Treatment of obstructive sleep apnea syndrome associated with stroke

The association between sleep-disordered breathing and stroke has been a subject of increased interest and research. Obstructive sleep apnea (OSA) is an important risk factor for stroke incidence and mortality. Moreover, OSA is a common clinical outcome after stroke, directly influencing the patients recovery. The treatment of choice for OSA is positive airway pressure (PAP) support and the PAP appliance is considered the most recommended clinical management for the treatment of patients with cardiovascular complications. However, the implementation of PAP in stroke patients remains a challenge, considering the increased frequency of motor and language impairments associated with the cerebrovascular event. In the present study, we reviewed the main findings describing the association between stroke and OSA treatment with continuous positive airway pressure. We also discussed the types of OSA treatment, the different options and indications of PAP treatment, PAP adherence and the clinical outcomes after treatment.

Cardiorespiratory response to exercise in men and women with obstructive sleep apnea

BACKGROUND OSA severity has been associated with self-reported lack of exercise. Most of the research has been done with men recruited from sleep clinics. There is limited data on the exercise performance of women with OSA. Therefore, the aim of this study was to assess exercise performance in a prospective, consecutive sample of men and women with OSA to compare their cardio respiratory parameters, arterial blood pressure and heart rate responses during and after exercise. METHODS Sixty-two subjects (32 men) completed the protocol. Men had a higher peak VO2, percent predicted peak VO2, VCO2, heart rate, systolic BP, and oxygen pulse than women. RESULTS There were no differences between men and women for peak oxygen saturation, peak Borg scales for dyspnea and leg fatigue and diastolic BP. A significant negative correlation was found between severity of OSA as measured by AHI, and peak VO2 (r=-0.4) in women, but not in men. CONCLUSION Men with OSA have higher peak VO2 and higher peak exercise heart rate than women with OSA; they also have higher end-exercise systolic BP than women and higher SBP during recovery from exercise; although this difference is not significant when adjusted for peak systolic BP. In men with OSA, there is no correlation between peak VO2 and AHI, but there is a significant correlation between these variables in women. Heart rate and blood pressure behaved similarly during exercise in both groups.

Cardiovascular profile in patients with obstructive sleep apnea

BACKGROUND Obstructive Sleep Apnea (OSA) is a risk factor for several cardiovascular conditions including increased cardiovascular mortality. It is therefore essential to know the major cardiovascular effects of sleep-disordered breathing during a clinical evaluation. OBJECTIVE To analyze the cardiovascular characteristics of patients with OSA. METHODS Patients underwent baseline polysomnography and were consecutively selected from the database of the Sleep Institute between March 2007 and March 2009. All patients were instructed to attend the clinic for blood collection, physical examination, 12-lead electrocardiogram, spirometry, cardiopulmonary exercise testing on a treadmill and transthoracic echocardiography. The study was approved by the Research Ethics Committee and recorded at http://clinicaltrials.gov/ under number: NCT00768625. RESULTS We analyzed 261 patients and 108 controls. The main characteristics of patients with OSA were: obesity, hypertension, low plasma levels of high density lipoprotein (HDL) and increased left atrial diameter compared with controls (3.75 ± 0.42; 3.61 ± 0.41, p = 0.001), respectively. These associated characteristics correspond to a 16.6 increase in the likelihood of OSA regardless of reporting any symptoms of this disorder, such as sleepiness or snoring. CONCLUSION In the sample studied, the mostly found cardiovascular profile of patients with OSA was: obesity, hypertension, low plasma levels of HDL and left atrial diameter increased.FUNDAMENTO: Apneia Obstrutiva do Sono (AOS) e um fator de risco para varias condicoes cardiovasculares incluindo aumento na mortalidade cardiovascular. Sendo assim, e essencial o conhecimento das principais repercussoes cardiovasculares dos disturbios respiratorios do sono durante uma avaliacao clinica. OBJETIVO: Analisar as caracteristicas cardiovasculares de pacientes com AOS. METODOS: Pacientes submetidos a polissonografia basal foram consecutivamente selecionados do banco de dados do Instituto do Sono entre marco de 2007 e marco de 2009. Todos os pacientes foram orientados a comparecer ao ambulatorio para coleta de sangue, exame fisico, eletrocardiograma de 12 derivacoes, espirometria, teste cardiopulmonar em esteira ergometrica e ecocardiograma transtoracico. O estudo foi aprovado pelo comite de etica e pesquisa e registrado no site http://clinicaltrials.gov/ sob o numero: NCT00768625. RESULTADOS: Foram analisados 261 pacientes e 108 controles. As principais caracteristicas dos pacientes com AOS foram: obesidade, hipertensao, baixos niveis plasmaticos de lipoproteinas de alta densidade (HDL) e aumento no diâmetro do atrio esquerdo quando comparados com controles (3,75 ± 0,42; 3,61 ± 0,41, p = 0,001), respectivamente. Essas caracteristicas associadas correspondem a um acrescimo de 16,6 vezes na probabilidade de ocorrencia de AOS independentemente do relato de algum sintoma dessa desordem, como sonolencia ou ronco. CONCLUSAO: Na amostra avaliada, o perfil cardiovascular dos pacientes com AOS mais encontrado foi: obesidade, hipertensao arterial, baixos niveis plasmaticos de HDL e atrio esquerdo com diâmetro aumentado.

Perfil cardiovascular em pacientes com apneia obstrutiva do sono

BACKGROUND Obstructive Sleep Apnea (OSA) is a risk factor for several cardiovascular conditions including increased cardiovascular mortality. It is therefore essential to know the major cardiovascular effects of sleep-disordered breathing during a clinical evaluation. OBJECTIVE To analyze the cardiovascular characteristics of patients with OSA. METHODS Patients underwent baseline polysomnography and were consecutively selected from the database of the Sleep Institute between March 2007 and March 2009. All patients were instructed to attend the clinic for blood collection, physical examination, 12-lead electrocardiogram, spirometry, cardiopulmonary exercise testing on a treadmill and transthoracic echocardiography. The study was approved by the Research Ethics Committee and recorded at http://clinicaltrials.gov/ under number: NCT00768625. RESULTS We analyzed 261 patients and 108 controls. The main characteristics of patients with OSA were: obesity, hypertension, low plasma levels of high density lipoprotein (HDL) and increased left atrial diameter compared with controls (3.75 ± 0.42; 3.61 ± 0.41, p = 0.001), respectively. These associated characteristics correspond to a 16.6 increase in the likelihood of OSA regardless of reporting any symptoms of this disorder, such as sleepiness or snoring. CONCLUSION In the sample studied, the mostly found cardiovascular profile of patients with OSA was: obesity, hypertension, low plasma levels of HDL and left atrial diameter increased.FUNDAMENTO: Apneia Obstrutiva do Sono (AOS) e um fator de risco para varias condicoes cardiovasculares incluindo aumento na mortalidade cardiovascular. Sendo assim, e essencial o conhecimento das principais repercussoes cardiovasculares dos disturbios respiratorios do sono durante uma avaliacao clinica. OBJETIVO: Analisar as caracteristicas cardiovasculares de pacientes com AOS. METODOS: Pacientes submetidos a polissonografia basal foram consecutivamente selecionados do banco de dados do Instituto do Sono entre marco de 2007 e marco de 2009. Todos os pacientes foram orientados a comparecer ao ambulatorio para coleta de sangue, exame fisico, eletrocardiograma de 12 derivacoes, espirometria, teste cardiopulmonar em esteira ergometrica e ecocardiograma transtoracico. O estudo foi aprovado pelo comite de etica e pesquisa e registrado no site http://clinicaltrials.gov/ sob o numero: NCT00768625. RESULTADOS: Foram analisados 261 pacientes e 108 controles. As principais caracteristicas dos pacientes com AOS foram: obesidade, hipertensao, baixos niveis plasmaticos de lipoproteinas de alta densidade (HDL) e aumento no diâmetro do atrio esquerdo quando comparados com controles (3,75 ± 0,42; 3,61 ± 0,41, p = 0,001), respectivamente. Essas caracteristicas associadas correspondem a um acrescimo de 16,6 vezes na probabilidade de ocorrencia de AOS independentemente do relato de algum sintoma dessa desordem, como sonolencia ou ronco. CONCLUSAO: Na amostra avaliada, o perfil cardiovascular dos pacientes com AOS mais encontrado foi: obesidade, hipertensao arterial, baixos niveis plasmaticos de HDL e atrio esquerdo com diâmetro aumentado.

Neurocognitive function in patients with residual excessive sleepiness from obstructive sleep apnea: a prospective, controlled study

OBJECTIVE This study aimed to evaluate neurocognitive function in adult patients with residual excessive sleepiness (RES) after appropriate treatment of obstructive sleep apnea (OSA) with CPAP and good adherence to treatment. METHODS This was a prospective controlled study. We included patients of both sexes, aged 35-60 years with OSA and an apnea-hypopnea index >20 ev/h, effectively treated with CPAP, but with a residual Epworth Sleepiness Scale score ≥11. The control group consisted of OSA patients adequately treated with CPAP who did not present with excessive sleepiness after treatment. Both groups underwent the following evaluations: polysomnography, multiple sleep latency testing, depression symptoms, and cognitive assessment. RESULTS Regarding baseline characteristics, the data were matched for age, years of study, and body mass index. Long-term memory result did not show a significant difference between the two groups (RES group 4.7 ± 2.0; control group 6.5 ± 1.9; p = 0.08). The executive functions were the most affected, with alterations in Wisconsin test, number of categories (RES group: 1.6 ± 1.4; control group: 3.0 ± 1.4; p = 0.01), and semantic verbal fluency test (RES group: 13.6 ± 3.3; control group: 16.9 ± 4.3; p = 0.04). CONCLUSION In summary, the mean depression scale score in the group with residual excessive sleepiness was significantly higher than that in the control group. Patients with residual excessive sleepiness showed impairment of executive functions but no impairments in other cognitive domains.

Evaluation and Validation of a Method for Determining Platelet Catecholamine in Patients with Obstructive Sleep Apnea and Arterial Hypertension

Background Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions. Objective In this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls. Methods In the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension. Results A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05). Conclusion Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.