Fátima Dumas Cintra

Impact of continuous positive airway pressure treatment on left atrial volume and function in patients with obstructive sleep apnoea assessed by real-time three-dimensional echocardiography

Background: Obstructive sleep apnoea (OSA) has been reported as a predictor of left ventricle (LV) diastolic dysfunction and left atrium (LA) remodelling. The aim of this study is to evaluate the impact of OSA treatment with a continuous positive airway pressure device (CPAP) on the LA volume and function, as well as on the LV diastolic function. Methods: In total, 56 OSA patients were studied. All patients underwent real-time three-dimensional (RT3DE) and two-dimensional echocardiogram with tissue Doppler evaluation in order to estimate LA volumes, function and LV diastolic performance. A total of 30 patients with an apnoea-hypopnoea index greater than 20 were randomly selected to receive sham CPAP (n = 15) or effective CPAP (n = 15) for 24 weeks. They underwent echo examination on three different occasions: at baseline, after 12 weeks and 24 weeks of CPAP or sham CPAP. Results: In the effective CPAP group we observed the following changes from the baseline to the 24-week echo evaluation: (a) a reduction in the E/E′ ratio (10.3 (1.9) to 7.9 (1.3), p = 0.03); (b) an increase in the LA passive emptying fraction (28.8% (11.9%) to 46.8% (9.3%), p = 0.01); and (c) a reduction in the LA active emptying fraction (42.7% (11.5%) to 25.7 (15.7), p<0.01). In the sham group, there were no changes from the baseline to the 24-week echo. We found a positive correlation between 24 week/baseline LA active emptying volume and 24 week/baseline E/E′ ratios (r = 0.40, p<0.05) and a negative correlation between 24 week/baseline LA passive emptying volume and 24 week/baseline E/E′ ratios (r = −0.53, p<0.05). No significant changes were found on LA total emptying fraction. Conclusion: CPAP improved LV diastolic function and LA passive emptying, but not LA structural variables in OSA patients. Trial registration number: NCT00768807.

Sleep-disordered breathing and chronic atrial fibrillation

BACKGROUND Little has been known about the prevalence of sleep apnea in patients with atrial fibrillation (AF). Studies have suggested that the prevalence of AF is increasing in patients with sleep-disordered breathing. We hypothesize that the prevalence of OSA is higher in chronic persistent and permanent AF patients than a sub-sample of the general population without this arrhythmic disorder. OBJECTIVE Evaluate the frequency of Obstructive Sleep Apnea in a sample of chronic AF compared to a sub-sample of the general population. METHODS Fifty-two chronic AF patients aged (60.5 +/- 9.5, 33 males) and 32 control (aged 57.3 +/- 9.6, 15 males). All subjects were evaluated by a staff cardiologist for the presence of medical conditions and were referred for polysomnography. The differences between groups were analyzed by ANOVA for continuous variables, and by the Chi-square test for dichotomous variables. Statistical significance was established by alpha=0.05. RESULTS There were no differences in age, gender, BMI, sedentarism, presence of hypertension, type 2 diabetes mellitus, abdominal circumference, systolic and diastolic blood pressure, and sleepiness scoring between groups. Despite similar BMI, AF patients had a higher neck circumference compared to control group (39.9cm versus 37.7cm, p=0.01) and the AF group showed higher percentage time of stage 1 NREM sleep (6.4% versus 3.9%, p=0.03). Considering a cut-off value for AHI >= 10 per hour of sleep, the AF group had a higher frequency of OSA compared to the control group (81.6% versus 60%, p=0.03). All the oxygen saturation parameters were significantly worse in the AF group, which had lower SaO(2) nadir (81.9% versus 85.3%, p=0.01) and mean SaO(2) (93.4% versus 94.3%, p=0.02), and a longer period of time below 90% (26.4min versus 6.7min, p=0.05). CONCLUSION Sleep-disordered breathing is more frequent in chronic persistent and permanent AF patients than in age-matched community dwelling subjects.

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.

Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea

OBJECTIVE To evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea. METHODS Thirteen male patients with severe obstructive sleep apnea (mean age 43±10 years with a mean body mass index of 26.7±1.9 kg/m2) received a single 50-mg dose of sildenafil or a placebo at bedtime. All-night polysomnography and heart rate variability were recorded. Frequency domain analysis of heart rate variability was performed for the central five-minute sample of the longest uninterrupted interval of slow wave and rapid eye movement sleep, as well as for one-minute samples during apnea and during slow wave and rapid eye movement sleep after resumption of respiration. RESULTS Compared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HFnu) components and a decrease in the low/high-frequency components of the heart rate variability ratio (LF/HF) in slow wave sleep (p<0.01 for both). Differences in heart rate variability parameters between one-minute post-apnea and apnea samples (Δ = difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of ΔLF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, ΔLF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (sR = −0.72 and −0.51, respectively, p= 0.01 for both), and ΔHFnu in rapid eye movement sleep was correlated with mean desaturation (sR= 0.66, p= 0.02) and the desaturation index (sR= 0.58, p = 0.047). CONCLUSIONS The decrease in arousal response to apnea/hypopnea events along with the increase in HFnu components and decrease in LH/HF components of the heart rate variability ratio during slow wave sleep suggest that, in addition to worsening sleep apnea, sildenafil has potentially immediate cardiac effects in patients with severe obstructive sleep apnea.

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.

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

BACKGROUND The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. METHODS Male OSA patients (apnea-hypopnea index [AHI]>5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. RESULTS We studied 266 males with OSA (age=48+/-13 y, body mass index=29+/-5 kg/m(2), AHI=34+/-25 events/h). HTN was present in 114 patients (43%) who were older (p<0.01), heavier (p<0.05) and had more severe OSA (p<0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p<0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast, the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR=1.12) and II genotype (OR=0.27). CONCLUSIONS Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe 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.

Executive functioning in obstructive sleep apnea syndrome patients without comorbidities: Focus on the fractionation of executive functions

Purpose: Obstructive sleep apnea syndrome (OSAS) is associated with impaired cognition, especially executive functions. However, various of its comorbid conditions are also known to cause cognitive impairment, so it is unclear whether OSAS itself is responsible for cognitive deficits. Our aim was to determine the effects of OSAS on executive functions in otherwise healthy patients. Method: This was a parallel group design study, which involved 22 patients aged 36–65 years diagnosed with moderate to severe OSAS, whose body mass index was below 26, and who did not have diabetes, hypertension, or depression. Controls were 22 healthy individuals with similar age, gender, intelligence quotient, and schooling to those of the patients. Participants completed a test battery that included measures of 6 distinct executive domains (shifting, inhibition, updating, dual-task performance, planning, and access to long-term memory), of all subsystems of the multiple-component working memory model, attention, and mood. Results: OSAS and controls were equivalent in all demographic variables and test scores. The apnea–hypopnea index did not significantly correlate with executive performance, but mean oxygen saturation did so with measurements of executive shifting and access to long-term memory. Conclusions: OSAS without comorbidities did not lead to cognitive impairment.

Alterações cardiovasculares na síndrome da apnéia obstrutiva do sono

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a prevalent condition in the general population. It is associated with increased cardiovascular risk and often goes unrecognized. Its diagnose requires a high degree of clinical suspicion, particularly on the part of cardiologists, and it may be confirmed by polysomnography. Continuous positive airway pressure (CPAP) therapy is highly effective, since it improves sleep breathing pattern, promotes restful sleep and thus enhances the quality of life of these patients, in addition to attenuating or reversing many cardiovascular complications related to OSAHS. This paper addresses the pathophysiology and clinical features of cardiovascular comorbidities associated with the syndrome.

Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

Background The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system. Results A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.