Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome.

Elevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non-rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end-apnoeic oxygen saturation and end-apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end-apnoeic systolic transmural pulmonary artery pressure (P(PATM)) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235+/-0.088 vs. 0.207+/-0.057 nmol/L). However, the highest levels were found during exercise (0.334+/-0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable.

Obstructive sleep apnea as a risk marker in coronary artery disease.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with a range of cardiovascular sequelae and increased cardiovascular mortality. The aim of our study was to assess the prevalence of OSA in patients with symptomatic angina and angiographically verified coronary artery disease (CAD). In addition, we analyzed the association of OSA and other coronary risk factors with CAD and myocardial infarction. METHODS: Overnight non-laboratory-monitoring-system recordings for detection of OSA was performed in 223 male patients with angiographically verified CAD and in 66 male patients with exclusion of CAD. A logistic regression analysis was performed to assess associations between risk factors and CAD and myocardial infarction. RESULTS: CAD patients were found to have OSA in 30.5%, whereas OSA was found in control subjects in 19.7%. The mean apnea/hypopnea index (AHI) was significantly higher (p < 0.01) in CAD patients (9.9 +/- 11.8) than in control subjects (6.7 +/- 7.3). Body-mass-index (BMI) was significantly higher in patients with CAD and OSA than in patients with CAD without OSA (28. 1 vs. 26.7 kg/m(2); p < 0.001). No significant difference was found with regard to other risk factors and left ventricular ejection fraction (LVEF) between both groups. Hyperlipidemia (OR 2.3; CI 1. 3-3.9; p < 0.005) and OSA defined as AHI >/=20 (OR 2.0; CI 1.0-3.8, p < 0.05) were independently associated with myocardial infarction. CONCLUSIONS: There is a high prevalence of OSA among patients with angiographically proven CAD. OSA of moderate severity (AHI >/=20) is independently associated with myocardial infarction. Thus, in the care of patients with CAD, particular vigilance for OSA is important.

[Cardiovascular morbidity in patients with obstructive sleep apnea in relation to the severity of respiratory disorder]. / Kardiovaskuläre Morbidität von Patienten mit obstruktiver Schlafapnoe in Abhängigkeit vom Schweregrad der Atmungsstörung.

BASIC PROBLEM AND OBJECTIVE: Untreated patients with obstructive sleep apnoea (OSA) have an increased risk of death from cardiovascular (cv) disease. This study was undertaken to determine the disease spectrum in patients with sonographically proven OSA (apnoea-hypopnoea index > or = 5), with special reference to cv risk factors and accompanying diseases in relation to the severity of their respiratory abnormalities. The study's aim was to clarify what risk factors and accompanying diseases were associated with different degrees of OSA. PATIENTS AND METHODS: A systematic recording of cv risk factors and accompanying diseases as well as their association to the severity of nocturnal respiratory disorders was made for 175 patients (165 men, 10 women, mean age 54 +/- 10.2 years) with sonographically proven OSA (mean apnoea-hypopnoea index 37 +/- 24.4). RESULTS: The body mass index (BMI) was significantly related to the severity of the respiratory disorder (apnoea-hypopnoea index, AHI, P < 0.05, odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.15-3.31). In a multivariate analysis, nocturnal breathing pause (P < 0.05; OR: 3.8; 95% CI: 1.3-11.1), left ventricular hypertrophy (P < 0.01; OR: 3.9; 95% CI: 1.5-10.3) and diabetes mellitus (P < 0.05; OR: 4.2, 95% CI: 1.2-14.7) were independently associated with a high-grade breathing disorder (AHI > or = 20). The incidence of left ventricular hypertrophy rose with an increasing severity of nocturnal OSA. CONCLUSION: These data indicate that in patients with high-grade OSA (AHI > or = 20) there is a further grouping together of cardiovascular risk factors, namely increasing body weight, diabetes mellitus, arterial hypertension and left ventricular hypertrophy; they explain the increased mortality rate among these patients from vascular complications.

Pulmonary haemodynamics in obstructive sleep apnoea: time course and associated factors.

Changes in pulmonary artery pressure within an obstructive apnoea and elevations of transmural pulmonary artery pressure (Ppa,tm) towards the end of apnoea are well known. The purpose of our study was to examine which factors contribute to the increase of Ppa,tm in an apnoea. In addition, the time course of Ppa,tm and associated factors during a sleep study was investigated. We analysed the association of changes in arterial oxygen saturation (Sa,O2), oesophageal pressure (Poes) to estimate intrathoracic pressure, systolic blood pressure (BPsys) to estimate left ventricular afterload, apnoea duration and the change in Ppa,tm (deltaPpa,tm) during the course of obstructive apnoeas. Consecutive apnoeas in nonrapid eye movement (NREM)-sleep at the beginning, the middle and the end of the sleep study were analysed in six patients with obstructive sleep apnoea. The mean systolic Ppa,tm was 28.0+/-12.1 mmHg at the beginning of apnoea and 38.6+/-15.5 mmHg at the end (deltaPpa,tm 10.5+/-7.4 mmHg; p<0.0001). DeltaSa,O2 (p<0.0001; odds ratio (OR) 1.45; confidence interval (CI) 1.20-1.76) and deltaPoes (p<0.0001; OR 1.22; CI 1.11-1.34) were independently associated with deltaPpa,tm in a multiple regression analysis. Apnoea duration as well as deltaPoes, deltaPpa,tm and deltaSa,O2 were all significantly higher (p<0.05) in apnoeas at the middle of the sleep study than at the beginning or the end. In conclusion, hypoxaemia and mechanical factors as an increase in negative thoracic pressure contribute to elevations of the transmural pulmonary artery pressure during an obstructive apnoea. The time course of pulmonary haemodynamics within a steep study reveals that the highest transmural pulmonary artery pressure occurs in the middle of the night with no progressive increase towards the end of the sleep study.

Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure.

Continuous positive airway pressure (CPAP) is the most widely used therapy for obstructive sleep apnoea (OSA). Despite its general efficacy, oxygen desaturation due to hypoventilation persists in some patients. The present study analysed the factors which are associated with this primary failure and, moreover, examined the effect of a bilevel positive airway pressure (BiPAP) trial. In a 15-month period, 13 patients with OSA (Group A) failed to respond to initial CPAP therapy defined by a remaining apnoea/hypopnoea index (AHI) of > or = 5 or a mean nocturnal SaO2 < 90%. These patients were compared to an age- and AHI-matched control group (Group B) successfully treated by CPAP. A logistic regression analysis was performed to identify factors which are associated with initial failure to CPAP. Patients of the CPAP-failure group were treated with nasal BiPAP in the control mode. These patients were significantly more obese than patients of the control group (mean body mass index 44.2 +/- 7.7 vs 31.2 +/- 6.3 kg m-2; P < 0.001). PaO2 at rest (P < 0.001) and at exercise (P < 0.005) was significantly lower in Group A patients. PaCO2 at rest (P < 0.001) was significantly higher in Group A patients and changed for the worse during exercise, whereas it improved in the control group. Group A patients spent significantly (P < 0.0001) more time with oxygen saturation < 90%. The percentage of time spent at < 90% of SaO2 was the only factor which was independently associated with the initial failure of CPAP (OR 1.13; 95% CI 1.0-1.2). After 3 months of treatment with BiPAP, the patients' blood gas values while awake improved significantly (P < 0.05) for PaO2 as well as for PaCO2. In conclusion, patients with OSA resistant to initial CPAP are morbidly obese with impaired awake blood gas values. The percentage of time spent at < 90% of nocturnal SaO2 is independently associated with initial failure of CPAP. BiPAP in the control mode is adequate for nocturnal ventilation, and improves awake blood gas values.

Predictive diagnostic value of clinical assessment and nonlaboratory monitoring system recordings in patients with symptoms suggestive of obstructive sleep apnea syndrome.

UNLABELLED: Obstructive sleep apnea syndrome (OSA) is of increasing importance because of its high prevalence and danger of morbidity to untreated patients. Diagnostic procedures need simplification. We evaluated the qualitative value of a stepwise diagnostic approach using clinical assessment and a home-based screening device according to current recommendations. METHODS: We investigated 114 patients with symptoms suggestive of obstructive sleep apnea syndrome by means of their clinical features, questionnaire responses, four-channel nonlaboratory monitoring (NLM) and full polysomnography. Operative indices in the diagnosis of OSA were calculated. RESULTS: A significant correlation (r = 0.7: p < 0.0001) was found between the oxygen desaturation index (ODI) and the respiratory disturbance index (RDI). The calculation of the difference between ODI by NLM and RDI by polysomnography showed a lack of agreement. Home-based monitoring revealed a high sensitivity (94%) but a low specificity (41%) in diagnosing OSA. However, a combination of clinical features, questionnaires and pulse oximetry achieved a specificity of 92%. CONCLUSION: Home-based monitoring provides reasonable negative predictive values in the diagnosis of OSA syndrome in symptomatic patients. It therefore qualifies as a screening method. Combined with clinical features and questionnaires it provides high positive predictive values and may therefore prove useful in simplifying diagnostic procedures.

[Community-acquired pneumonia requiring inpatient treatment: outcome and prognostic rule]. / Stationär behandlungspflichtige ambulant erworbene Pneumonien: Ausgang und prognostische Regel.

OBJECTIVE: Mortality in community-acquired pneumonia (CAP) may be reduced by early identification of patients requiring intensive care treatment. The purpose of the study was to determine prognostic factors of outcome in patients with CAP in order to establish a clinically applicable discriminant rule. METHODS: 93 episodes of 92 patients with CAP were reviewed with regard to epidemiological, clinical, laboratory and microbiologic data. The prognostic analysis included a univariate as well as a multivariate approach in order to identify parameters correlated with death using the Cox regression hazard function in a backward stepwise selection model. The three parameters found to contribute most to the significance of the model were used in a discriminant rule for classification of outcome. RESULTS: The parameters found to be significantly different between survivors and non-survivors were heart rate, systolic, diastolic as well as mean blood pressures, leucocyte count, percentage of laymphocytes, and LDH values. The multivariate analysis revealed that heart rate, systolic arterial pressure, and LDH serum levels were associated best with lethal outcome (overall significance of the model p < 0.005). A prognostic rule composed of the variables heart rate > or = 90 beats/min, systolic arterial blood pressure < or = 80 mmHg and LDH > or = 260 U/l achieved a sensitivity of 77%, a specificity of 75% and positive and negative predictive values of 42% and 93%, respectively. It was associated with a 6-fold increased risk of lethal outcome. CONCLUSIONS: Heart rate, systolic blood pressure, and LDH values were associated best with death in a multivariate analysis. A discriminant rule consisting of these three variables achieved favourable classification results. The rule qualifies for further prospective validation and may prove useful in the management of hospital treated CAP.

[Sleep apnea as a risk marker in coronary heart disease]. / Schlafapnoe als Risikomarker bei koronarer Herzkrankheit.

UNLABELLED: Obstructive sleep apnea (OSA) and coronary heart disease (CHD) are both frequent in the middle ages. Both disease share a similar spectrum or risk factors and attendant diseases. The aim of the study was to determine the prevalence of obstructive sleep apnea in patients with coronary heart disease diagnosed by coronary angiography. Furthermore, influence of sleep apnea and attendant diseases and risk factors for coronary heart disease, especially the risk for myocardial infarction and reduced left ventricular ejection fraction, was investigated. We included in this study 143 patients (121 men, 22 women mean age 60 +/- 8 years (35-81) who underwent coronary angiography because of angina pectoris or were suspicious for CHD due to noninvasive investigations. These patients has symptoms of OSA based on a standardized questionnaire. They underwent a four-channel screening with a non-laboratory-monitoring-system (NLMS) for detection of sleep-related breathing disorders. In addition, spectrum of risk factors and concomitant diseases were considered. Sleep apnea was more frequent in patients with CHD (30.6%) in comparison to patients without CHD (21.8%), but did not reach statistical significance. Patients with CHD and OSA had a significantly higher frequency of a history of myocardial infarction and had a significantly lower left ventricular ejection fraction than patients without OSA. IN CONCLUSION: Patients with the combination of OSA and CHD are at higher risk for myocardial infarction and reduced left ventricular ejection fraction. Patients with CHD should be screened for OSA in case of secondary prevention.

Bronchopulmonary infection with Mycobacterium malmoense presenting as a bronchoesophageal fistula.

We report a bronchopulmonary infection with Mycobacterium malmoense in a patient with severe immunosuppression due to insulin-dependent diabetes mellitus, humoral immunodeficiency after thymoma (Good's syndrome) and prolonged immunosuppressive treatment after myasthenic crisis. It presented as non-resolving pneumonia of the left lower lobe. Bronchoscopically, a bronchoesophageal fistula was detected. Numerous acid-fast organisms were found in the sputum specimen and in the bronchial biopsy around the fistula. M. malmoense was isolated from sputum, bronchoalveolar lavage and bronchial biopsy. Whereas conventional in vitro susceptibility testing revealed susceptibility only to ethambutol, multi-drug susceptibility testing confirmed susceptibility to rifampicin, ethambutol, clarithromycin and prothionamide. The clinical outcome after 12 months of therapy resulted in a stable remission and considerable suppression of the mycobacterial load, but not in complete eradication.

Value of routine microbial investigation in community-acquired pneumonia treated in a tertiary care center.

The study was conducted at a tertiary care and teaching hospital with about 200 beds for internal medicine. The objective was to determine the diagnostic yield and value in directing antibiotic therapy of a routine microbial approach in patients with community-acquired pneumonia referred to a tertiary care center. We studied 93 episodes in a retrospective study. 69/93 (74%) cases were treated with at least one empirical antibiotic therapy prior to admission. Microbial investigation was performed in 83/93 cases (89%). An etiological agent was established in 19/83 (23%) cases including 7/50 (14%) by blood culture and 12/52 (23%) by serology. Bronchoscopy with 18 protected specimen brush and 20 bronchoalveolar lavage examinations was definitely diagnostic in only 1/25 (4%) cases, and this case was also identified by blood culture. 5/25 (20%) were probably diagnostic. Three pathogens, Streptococcus pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila, accounted for 15/19 (79%) of the identified agents. The diagnostic results directed a change in antibiotic therapy in 6/19 (32%) of cases with definitely proven pathogens. 4/19 (21%) of cases would have been treated with an inappropriate regimen without diagnostic results. The diagnostic yield of routine microbial investigation in pretreated patients is low. The routine approach reveals its limited value especially in patients with severe courses. The role of bronchoscopy remains to be defined for patients with severe (and pretreated) community-acquired pneumonia.

[Sleep apnea and cardiovascular risk]. / Schlafapnoe und kardiovaskuläres Risiko.

Obstructive sleep apnea syndrome (OSAS) is the most important form of sleep-related breathing disorders due to its high prevalence and its potential for developing cardiovascular diseases. The increased morbidity of these patients is explained by the coincidence with cardiovascular diseases, and the increased mortality of untreated patients is due to cardiovascular complications, which depend on the degree of the breathing disorder. Heavy snoring, as a partial obstruction of the upper airways, and OSAS are independent risk factors for the development of cardiovascular diseases and stroke. Causal associations exist between acute hemodynamic changes, pressure and volume load, changes in the humoral and the central nervous system, and blood gas alterations during the obstructive apnea and the long-term condition due to OSAS. Obstructive apnea can be divided into an early phase, a late phase, and a phase of the postapneic hyperventilation with respect to hemodynamic changes, blood gas alterations, and the autonomic nervous system. The most striking changes in these parameters are seen at the end of apnea and in the first resumption of breathing, with an increase in systemic and pulmonary blood pressure, decrease in stroke volume, and a distinct change in heart rate. Manifestation of systemic hypertension even in the awake state is promoted by changes in the volume system, with activation of neurohumoral changes and by a resetting of baro- and chemoreceptors. Similar mechanisms are discussed in the development of pulmonary hypertension. In this circumstance the role of hypoxemia as a causal factor for pulmonary hypertension or as a consequence due to structural changes of the pulmonary vessels is controversial. OSAS is frequent in patients with coronary heart disease and these patients must be classified as a particular risk group because of apnea-associated silent myocardial ischemia and electric instability of the myocardium. The occurrence of arrhythmia in patients with OSAS is closely related to the apnea and hyperventilation events and depends on the sympathovagal balance. Early diagnosis and suitable therapy of patients at risk not only abolishes the sleep-related breathing disorder but also improves long-term outcome.

Predicting in-hospital outcome in HIV-associated Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life-threatening complication in the course of HIV infection. Despite effective treatment, mortality may still be as high as 10%. The identification of risk factors associated with a lethal outcome might be helpful as a guide to therapy for patients at risk and in the evaluation of new drugs with anti-pneumocystic activity. In a retrospective study 58 first episodes of HIV-associated PCP without prophylaxis were analyzed. Variables associated univariately with higher mortality were identified. A prognostic rule was established in a multivariate approach using canonical discriminant analysis. Cut-off values for parameters included were determined in order to allow a clinically applicable estimate of the individual risk. Variables associated with early mortality were hemoglobin, hematocrit, platelet count, albumin, total protein, gamma-globulins, and AaDO2. LDH values, percentage of neutrophils in the BAL, as well as the cellular immunologic state as indicated by CD4-cell count were not significantly associated with the outcome. The discriminant function yielded the best classification results with the inclusion of hemoglobin, albumin, and gamma-globulins (overall accuracy 86%). Two or more of the following parameters were associated with a 14-fold increased risk of in-hospital mortality: hemoglobin less than 10 g/dl, albumin less than 3 g/dl, and gamma-globulins less than 1.2 g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV-associated PCP with a positive prognostic rule have a 14-fold increased risk for in-hospital lethal outcome. This discriminant rule may be helpful in identifying patients at risk.

[Life style changes in patients with myocardial infarct in the framework of intramural and ambulatory rehabilitation--results of a German pilot study]. / Lebensstiländerung bei Herzinfarktpatienten im Rahmen der stationären und ambulanten Rehabilitation--Ergebnisse einer deutschen Pilotstudie.

To assess whether German patients would make comprehensive lifestyle changes as designed and successfully tested in the San Francisco Lifestyle Heart Trial, we recruited 25 patients who received usual care, and 15 patients who made lifestyle changes during a 6-week in-hospital rehabilitation program followed by a 3-month ambulatory period. The intervention program consisted of a low-fat vegetarian diet, stress management techniques, aerobic exercises, and group support meetings. The program was well accepted, and high compliance resulted in significant changes in the patients' diet, stress management, and exercise activity. For instance, fat intake dropped from 36% to 9% of total calories. As patients in both groups received 20 mg/day of Pravastatin, a lipid-lowering drug, lipid levels dropped significantly in both groups (30% in the intervention group and 27% in the control group). Thus, the combined effect of behavioral and drug treatment did not result in a substantial additional lipid-lowering effect. Within the intervention group significant improvement in quality of life occurred. In conclusion, the lifestyle heart program can be successfully implemented in a German rehabilitation setting which combines in-hospital and out-patient activities. However, participation in the current program is limited to highly motivated, well educated coronary patients.

Prognostic analysis and predictive rule for outcome of hospital-treated community-acquired pneumonia.

In community-acquired pneumonia (CAP) mortality may be reduced by early identification of patients requiring intensive care treatment. The purpose of this study was to determine prognostic factors of outcome in patients with CAP in order to establish a clinically applicable discriminant rule. Ninety three episodes of CAP in 92 patients were retrospectively reviewed with regard to epidemiological, clinical, laboratory and microbiological data. The prognostic analysis included a univariate as well as a multivariate approach, in order to identify parameters associated with death using the Cox regression hazard function in a backward stepwise selection model. The three parameters found to contribute most to the significance of the model were used in a discriminant rule for classification of outcome. The parameters found to be significantly different between survivors and non-survivors were heart rate, systolic and diastolic as well as mean blood pressures, leucocyte count, percentage of lymphocytes, and lactate dehydrogenase (LDH) values. The multivariate analysis revealed that heart rate, systolic arterial pressure, and LDH serum levels were most closely associated with fatal outcome. A prognostic rule composed of the variables heart rate > or = 90 beats.min-1, systolic arterial blood pressure < or = 80 mmHg, and LDH > or = 260 U.l-1 achieved a sensitivity of 77%, a specificity of 75%, and positive and negative predictive values of 42 and 93%, respectively. It was associated with a six fold increased risk of fatal outcome. In conclusion, heart rate, systolic blood pressure, and LDH values were most closely associated with death in a multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sleep-related respiratory disorders in patients with implantable cardioverter/defibrillator devices--relationship between left ventricular function and respiratory disorder]. / Schlafbezogene Atmungsstörungen bei Patienten mit implantierbarem Cardioverter/Defibrillator (ICD)--Beziehung zwischen linksventrikulärer Funktion und Atmungsstörung.

In order to detect sleep related breathing disorders (SRBD), 15 patients (6 with dilated cardiomyopathy [DCM], 9 with coronary heart disease [CHD], mean age 58 +/- 13 years) with implantable cardioverter/defibrillator [ICD] underwent polysomnography. A SRBD could be diagnosed in 27% of cases (n = 4; 3 DCM, 1 CHD). The reduction of the ejection fraction (EF) (normal, mild-to-moderate and severe, respectively) and the quality of sleep-related disturbances (normal, obstructive, and central/periodic) were significantly associated. In addition, in patients with DCM, the reduction of the EF correlated significantly with the amount of nocturnal oxygen-desaturation.