Acute hemodynamic effects of non-invasive ventilation in patients with obesity hypoventilation syndrome.

OBJECTIVE: To evaluate the acute effects of volume-targeted non-invasive ventilation (NIV) on hemodynamic parameters assessed by impedance cardiography in patients with obesity hypoventilation syndrome (OHS). BACKGROUND: Despite the well-described beneficial effects of NIV using volume-targeted pressure support ventilation modes on respiration in OHS patients, questions were raised about the impact of this treatment on the cardiovascular system. METHODS: In 15 patients (10 men; mean age, 55.8±9.3 years) impedance cardiography recordings were taken at baseline, after 120 minutes while on NIV and 20 minutes after NIV termination. A repeated-measures analysis of variance was used for comparisons. RESULTS: Compared to baseline, a reduction in heart rate (from 80±11 to 73±10 beats per min, p<0.05) was observed on NIV whereas the stroke volume and cardiac index remained stable throughout all three assessed intervals (p=0.347, p=0.344; respectively). The pre-ejection period increased on NIV (from 113±16 to 127±20 ms, p<0.05), and the left ventricular ejection time increased after NIV termination compared to baseline (from 259±25 to 269±25 ms, p<0.05). CONCLUSION: Volume-targeted NIV may acutely improve systolic time intervals without any negative impact on the left ventricular function in OHS patients (Tab. 2, Ref. 17).

Skin wound healing in obese and lean male adolescent rats submitted to pre-weaning litter size manipulation.

We investigated whether early postnatal over-nutrition affects normal course of skin wound healing. To induce over-nutrition the litter size was adjusted on the first day after birth to four pups/nest (small litters). In parallel, as a control, normal nests of 10 pups/nest (normal litters) were used. For the wound healing experiment 30 male Sprague-Dawley rats, 15 from normal nests and 15 from small nests, were used. Two parallel full-thickness skin incisions and two full-thickness excisions were performed on the back of each rat. Samples for histological examination (excisions) and wound tensile strength measurement (incisions) were collected on days 2, 6, and 14 after surgery. Our study demonstrates that rats from the small nests had enhanced plasma levels of insulin and enhanced body weight/fat parameters. Furthermore, in small nests, rats that expressed the above-mentioned symptoms displayed slight improvement of epidermis regeneration, accelerated demarcation line formation, and increased wound tensile strength. From this point of view the small nest model used in the present experiment is helpful for exploration whether these acquired changes might be considered as a sufficient essential factor involved in the regulation of metabolic homeostasis and wound repair in juvenile obese male rats. Nevertheless, further studies need to be performed to verify the present findings also on other animal models and humans and to describe the exact underlying mechanism.

Long-term myocardial effects of noninvasive ventilation in patients with obesity hypoventilation syndrome.

INTRODUCTION: Chronic effects of noninvasive ventilation on myocardial function in patients with obesity hypoventilation syndrome (OHS) are scarcely understood. The aim of the present study was to evaluate the long-term effects of volume-targeted bilevel positive airway pressure ventilation (BiPAP) on cardiac parameters and myocardial biomarkers in patients with OHS. METHODS: Clinically stable patients with OHS referred to the tertiary center for the initiation of long-term BiPAP therapy were consecutively enrolled. At baseline, all participants underwent overnight cardiorespiratory polygraphy. BiPAP therapy using volume-targeted spontaneous/timed mode delivered via an oro-nasal mask was initiated. Beat-to-beat noninvasive monitoring by impedance cardiography was used to assess heart function at baseline and after 3 and 12 months of BiPAP use. Serum troponin 1, N-Terminal Pro-B-Type Natriuretic Peptide (NT-ProBNP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were monitored. RESULTS: Thirteen patients (10 men; mean age, 55.8 ± 9.8 years; mean body mass index of 47.8 ± 5.9 kg/m2) were recruited. From baseline to 3, and to 12 months of BiPAP use, left ventricular stroke volume (SV), ejection time (LVET), and ejection time index significantly increased (P = 0.030; P < 0.001; P = 0.003, respectively), while heart rate and systolic time ratio significantly decreased (P = 0.004; P = 0.034, respectively). Reductions in serum NT-proBNP, IL-6 and TNF-α were observed (P = 0.045; P = 0.018; P = 0.003, respectively). No significant changes in serum troponin were detected throughout the study. CONCLUSIONS: The present findings of increased SV, in association with lengthening of LVET, reductions of NT-proBNP and reductions in circulatory inflammatory markers in patients with stable OHS and chronic moderate-to-severe daytime hypercapnia treated with BiPAP over 1 year support the role of this therapeutic mode in such patients.

Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes.

Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study. Genotyping for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was performed using real-time PCR with subsequent melting-curve analysis. SLC47A1 rs2289669 genotype was significantly associated with the reduction in haemoglobin A1c (HbA1c) after 6 months. Twenty percentage of patients with diabetes that are homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison with the patients carrying G-allele (GG + GA: 0.55 ± 0.09% vs. AA: 1.10 ± 0.18%, p = 0.018). In conclusion, the results of this study might have in future practical implication in personalised treatment of patients with type 2 diabetes.

The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories.

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean±sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h(-1)) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m(-2)) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h(-1), p<0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.

Effect of sulphonylurea treatment on glycaemic control is related to TCF7L2 genotype in patients with type 2 diabetes.

The aim of the present study was to analyse effects of sulphonylurea treatment on parameters of glycaemic control in relation to transcription factor 7-like 2 (TCF7L2) genotypes. In 87 patients with type 2 diabetes who failed to achieve glycaemic control on metformin monotherapy, effects of 6-month sulphonylurea in addition to metformin on reductions in haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels were evaluated. Reduction in HbA1c and FPG in response to 6-month sulphonylurea treatment was significantly higher in patients with CC genotype compared to those with the CT+TT genotype (1.16 ± 0.07 vs. 0.86 ± 0.07%, p = 0.003; 1.57 ± 0.12 vs. 1.14 ± 0.14 mmol/l, p = 0.031, respectively). In the multivariate analysis, baseline HbA1c and the TCF7L2 genotype were the only significant predictors of HbA1c reduction. In conclusion, the magnitude of HbA1c and FPG reductions after 6-month sulphonylurea treatment in addition to metformin is related to the TCF7L2 gene polymorphism.

Carotid intima-media thickness in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Several large population-based cohort studies identified an association between reduced lung function and increased intima-media thickness (IMT). Nevertheless, a vast majority of subjects in these studies did not suffer from COPD and thus it remains unclear whether IMT differs among various stages of COPD severity. The aim of the present pilot study was to evaluate IMT in central European patients with moderate, severe and very severe COPD. METHODS: In forty-nine patients (34 men, 15 women; mean age 66.1 +/- 10.9 years) with COPD, the combined thickness of intima and media layers of the common carotid arteries was measured using B-mode ultrasound imaging. RESULTS: Increased cardiovascular disease risk as evidenced by carotid IMT values greater or equal to 75th percentile were present in 14 (28.6%), whereas IMT hypertrophy (IMT values greater or equal 0.80 mm) was present in 24 (49.0%) of patients. Average IMT in the entire cohort was 0.85 +/- 0.21 mm, with no significant differences from stage II to stages III and IV of COPD. CONCLUSION: Present results indicate a high prevalence of IMT hypertrophy and increased cardiovascular disease risk as assessed by carotid ultrasonography in COPD patients with a broad spectrum of airway obstruction severity. The lack of differences in carotid IMT between various stages of lung impairment severity suggests that atherosclerosis starts early in the course of COPD. Therefore, the need to screen patients for the presence of concomitant atherosclerosis in early stages of COPD severity may be warranted (Tab. 2, Ref. 33).

[Experimental use of the recipient's epithelial cells in tracheal allotransplantation--initial outcomes]. / Vyuzitie epiteliálnych buniek príjemcu pri allotransplantácii trachey v experimente--prvé výsledky.

The management of long tracheal lesions requires development of tracheal implants, which would enable resection combined with anastomosis. The authors' scientific study is based on tracheal allotransplantation on an animal model (sheep), using tracheal epithelial cells of the recipient. The project covers preparation of the graft, so that all components of the major histocompatibility complex (MHC), which participate in graft rejection, are removed. Histological examination of the allograft with cultivated epithelial cells showed its good healing with revasculatization and with no signs of graft rejection.

[Osteoporosis in chronic obstructive pulmonary disease]. / Osteoporóza pri chronickej obstrukcnej chorobe pl'úc.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis because of their age, limited physical activity, low body mass index, smoking, hypogonadism, malnutrition, and use of corticosteroids. Systemic inflammation represents an additional pathomechanism contributing to the development of osteoporosis in COPD patients. Males in their mid to late 60s with a smoking history of greater than 60 pack-years have a prevalence rate of vertebral fractures similar to, and possibly greater than, postmenopausal women greater than or equal to 65 years old: in patients with severe COPD, up to 50-70% have osteoporosis or osteopenia, and up to 24-30% have compression vertebral fractures. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Systemic corticosteroids remain the most common cause of drug-related osteoporosis, and a meta-analysis concluded that the use of more than 6.25 mg prednisone daily led to decreased bone mineral density (BMD) and increased fracture risk. In contrast, the effects of the long-term use of inhaled corticosteroids on BMD remain debatable. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only but the recommendations follow the general recommendations for the diagnosis and treatment of osteoporosis. Early recognition of BMD loss is essential, and assumes close interdisciplinary cooperation between respirologists and reumatologists. Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted. In the future, novel therapeutical strategies such as monoclonal antibodies against osteoclasts activators may prove their beneficial effects in the treatment of COPD-related osteoporosis.

Immunohistochemical markers of proliferation and vascularisation in preneoplastic bronchial lesions and invasive non-small cell lung cancer.

Autofluorescence bronchoscopy (AFB) has been shown to be sensitive to detect preneoplastic lesions in central lung airways system. In early stages of carcinogenesis, up-regulation of cyclooxygenase (COX)-2, Ki67 and/or increased angiogenesis may play a role by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and setting up of the metastatic process. The present study compared the expression of proliferative (COX-2, Ki67 and PCNA) and angiogenic markers (CD34 and NG2) between preneoplastic bronchial squamous dysplasia lesions and invasive squamous cell carcinoma. Biopsies obtained during AFB [preneoplastic lesions: low-grade (lesions up to moderate dysplasia), n=13; high-grade lesions (severe dysplasia), n=12] and surgical specimens (resections of bronchogenic carcinoma, n=11) were stained with COX-2, Ki67, PCNA, CD34 and NG2 monoclonal antibodies. Microvessel density (MVD) was analysed based on anti-CD34 immunostaining. Lesions were positive for COX-2 in 12 out of 25 preneoplastic lesions, and in 10 out of 11 invasive carcinomas (p=0.025). In preneoplastic lesions, the mean percentage of Ki67 positive cells was lower compared to invasive carcinomas (37.4+/-5.8 versus 58.6+/-8.4%, p=0.043). In addition, significant differences in MVD were observed between preneoplastic and NSCLC specimen [35.3 (25.9, 61.9) versus 22.1 (20.1, 32.6), p=0.016]. No differences were observed in the mean percentage of PCNA or NG2 positive cells between preneoplastic lesions and invasive carcinomas. Findings of the present study indicate that increases in COX-2 and Ki67 expression may be associated with the development of bronchogenic carcinomas and possibly with acquisition of an invasive phenotype. In contrast, increased CD34 expression in preneoplastic lesions suggests that increased MVD may represent an early marker of lung carcinogenesis.

Circulating lipopolysaccharide-binding protein and carotid intima-media thickness in obstructive sleep apnea.

Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1+/-10.3 to 32.3+/-10.9 to 38.1+/-10.3 microg.ml(-1), p=0.015; from 0.52+/-0.09 to 0.58+/-0.06 to 0.62+/-0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r(2)=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p<0.001, r(2)=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients.

Blood pressure and heart rate variability response to noninvasive ventilation in patients with exacerbations of chronic obstructive pulmonary disease.

Sympathetic activation and parasympathetic withdrawal are commonly observed during acute exacerbations of chronic obstructive pulmonary disease (COPD). We have demonstrated previously that noninvasive positive-pressure ventilation (NPPV) improves parasympathetic neural control of heart rate in patients with obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial effects in COPD as well. Therefore, we assessed the acute effects of NPPV on systemic blood pressure and indexes of heart rate variability (HRV) in 23 patients with acute exacerbations of COPD. The measurements of HRV in the frequency domain were computed by an autoregressive spectral technique. The use of NPPV resulted in significant increases of oxygen saturation (from 89.2+/-1.0 to 92.4+/-0.9 %, p<0.001) in association with reductions in systolic and diastolic blood pressures and heart rate (from 147+/-3 to 138+/-3 mm Hg, from 86+/-2 to 81+/-2 mm Hg, from 85+/-3 to 75+/-2 bpm, p<0.001 for all variables), and increases in ln-transformed high frequency band of HRV (from 6.4+/-0.5 to 7.4+/-0.6 ms(2)/Hz, p<0.01). Reductions in heart rate and increases in ln-transformed HF band persisted after NPPV withdrawal. In conclusion, these findings suggest that NPPV may cause improvements in the neural control of heart rate in patients with acute exacerbations of COPD.

The association between oxidative stress and obstructive lung impairment in patients with COPD.

An oxidant/antioxidant imbalance is thought to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that antioxidant capacity reflected by erythrocyte glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities, and serum levels of the lipid peroxidation product malondialdehyde (MDA), may be related to the severity of obstructive lung impairment in patients with COPD. Erythrocyte GPx, SOD and CAT activities, and serum levels of MDA were measured in 79 consecutive patients with stable COPD. Pulmonary functional tests were assessed by body plethysmography. Moderate COPD (FEV1 50-80%) was present in 23, and severe COPD (FEV1 < 50%) in 56 patients. Erythrocyte GPx activity was significantly lower, and serum MDA levels were significantly higher in patients with severe COPD compared to patients with moderate COPD (GPx: 43.1+/-1.5 vs. 47.7+/-2.9 U/gHb, p<0.05, MDA: 2.4+/-0.1 vs. 2.1+/-0.1 nmol/ml, p<0.05). Linear regression analysis revealed a significant direct relationship between FEV1 and erythrocyte GPx activity (r = 0.234, p<0.05), and a significant inverse relationship between FEV1 and serum MDA levels (r = -0.239, p<0.05). However, no differences were observed in the erythrocyte SOD and CAT activities between the two groups of patients with different severity of COPD. Findings of the present study suggest that antioxidant capacity reflected by erythrocyte GPx activity and serum levels of the lipid peroxidation product MDA are linked to the severity of COPD.

Endobronchial actinomycosis presenting as haemoptysis.

Actinomycosis is an infrequent chronic progressive granulomatous and suppurative disease caused by Actinomyces israelii, a natural inhabitant of the gastrointestinal tract. We report a rare case of a 68-year-old man with primary endobronchial actinomycosis who presented in the emergency respiratory ward with massive hemoptysis and dyspnea. An urgent fiberoptic bronchoscopy revealed hypertrophic mucosa and a narrowed lingular bronchus with a pale extruding exophyt. Diffuse bleeding from the mucosa adjacent to the exophyt was present. Histopathologic evaluation revealed chronic inflammation with abscess formation and clusters of Actinomyces colonies. Therapy with clindamycin maintained for 7 weeks prevented recurrence of the disease. In the light of our case and the review of literature we conclude that early recognition of primary endobronchial actinomycosis associated with hemoptysis and proper antibiotic treatment are essential to prevent undesirable complications including unwarranted surgery (Fig. 2, Ref. 30). Full Text (Free, PDF) www.bmj.sk.

Inhaled corticosteroids and survival in COPD patients receiving long-term home oxygen therapy.

BACKGROUND: Several observational studies suggest that therapy with inhaled corticosteroids (ICS) is associated with reduced mortality in patients with chronic obstructive pulmonary disease (COPD). However, none of these has reported survival data in COPD patients with respiratory insufficiency who require domiciliary oxygen therapy. The present study was conducted to examine the association between ICS and all-cause mortality in patients with severe COPD and chronic hypoxemia. PATIENTS AND METHODS: From a tertiary referral clinic, we identified 145 consecutive COPD patients who met the criteria for long-term oxygen therapy between 1996 and 2002. We compared the hazard ratio (HR) for all-cause mortality over 1 year between patients who were (n=55) and were not treated with ICS (n=90). RESULTS: In a crude analysis, the use of ICS was associated with a HR of 0.38 (95% confidence interval (CI)=0.18-0.79). After adjustments for age, sex, use of oral steroids, and beta2-agonists, PaO2 and PaCO2, the HR was 0.46 (95% CI=0.21-0.98). CONCLUSIONS: Our findings indicate that ICS may reduce all-cause mortality in patients with severe COPD and chronic hypoxemia, who require long-term domiciliary oxygen therapy. These data suggest that ICS may play an important role in improving clinical outcomes in patients with advanced COPD.

Increased resting energy expenditure and insulin resistance in male patients with moderate-to severe obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) has been associated with disturbances in energy metabolism and insulin resistance, nevertheless, the links between OSA severity, resting energy expenditure (REE) and insulin resistance (homeostasis model assessment, HOMA-IR) remained unexplored. Therefore, we investigated the effects of OSA severity on REE, and relationships between REE and HOMA-IR in patients with OSA. Forty men [mean (SD) age 49.4 (11.4) years] underwent overnight polysomnography; REE was assessed using indirect calorimetry. REE adjusted for fat-free mass (FFM) was higher in patients with moderate-to severe OSA [n=24; body mass index (BMI) 31.1 (2.7) kg.m(-2); apnoea-hypopnoea index (AHI)>/=15 episodes.h(-1)] compared to participants with no clinically significant OSA (n=16; BMI 30.3 (2.2) kg.m(-2); AHI<15 episodes.h(-1)) [median (interquartile range) 30.4 (26.1-31.3) versus 25.8 (24.6-27.3) kcal.kg(-1).24 h(-1), p=0.005)]. AHI and oxygen desaturation index (ODI) were directly related to REE/FFM (p=0.001; p<0.001, respectively) and to HOMA-IR (p<0.001 for both). In stepwise multiple linear models, REE/FFM was independently predicted by ODI (p<0.001) and age (p=0.028) (R(2)=0.346); HOMA-IR was independently predicted by ODI only (p<0.001, R(2)=0.457). In conclusion, male patients with moderate-to severe OSA have increased REE paralleled by impaired insulin sensitivity. Severity of nocturnal intermittent hypoxia reflected by ODI is an independent predictor of REE/FFM and HOMA-IR.

Effect of continuous positive airway pressure on mitral regurgitant fraction and atrial natriuretic peptide in patients with heart failure.

OBJECTIVES: We sought to determine the effects of continuous positive airway pressure (CPAP) on mitral regurgitant fraction (MRF) and plasma atrial natriuretic peptide (ANP) concentration in patients with congestive heart failure (CHF). BACKGROUND: In patients with CHF, elevated plasma ANP concentration is associated with elevated cardiac filling pressures. Secondary mitral regurgitation may contribute to elevation in plasma ANP concentration in patients with CHF. Because CPAP reduces transmural cardiac pressures and left ventricular (LV) volume, we hypothesized that long-term CPAP application would decrease the MRF and plasma ANP concentration in patients with CHF and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). METHODS: Seventeen patients with CHF and CSR-CSA underwent baseline assessments of plasma ANP concentration and left ventricular ejection fraction (LVEF) and MRF by radionuclide angiography. They were then randomized to receive nocturnal CPAP plus optimal medical therapy (n = 9) or optimal medical therapy alone (n = 8) for 3 months and were then reassessed. RESULTS: In the CPAP-treated group, LVEF increased from (mean +/-SEM) 20.2 +/- 4.2% to 28.2 +/- 5.3% (p < 0.02); MRF decreased from 32.8 +/- 7.7% to 19.4 +/- 5.5% (p < 0.02); and plasma ANP concentration decreased from 140.9 +/- 20.8 to 103.9 +/- 17.0 pg/ml (p < 0.05). The control group experienced no significant changes in LVEF, MRF or plasma ANP concentration. Among all patients, the change in plasma ANP concentration from baseline to 3 months correlated significantly with the change in MRF (r = 0.789, p < 0.0002). CONCLUSIONS: In patients with CHF, CPAP-induced reductions in MRF and plasma ANP concentration in association with improvements in LVEF indicate improved cardiac mechanics. Our findings also suggest that reductions in plasma ANP concentration were at least partly due to reductions in MRF.

Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea.

OBJECTIVES: To determine the acute effects of continuous positive airway pressure (CPAP) on baroreceptor reflex sensitivity (BRS) for heart rate during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). DESIGN AND METHODS: In eight CHF patients with OSA not previously treated with CPAP, spontaneous BRS was assessed during overnight polysomnography prior to the onset of sleep, and during stage 2 non-rapid eye movement sleep (NREM) before, during and after application of CPAP. RESULTS: CPAP alleviated OSA and acutely increased the slope of BRS (median, 25%,75%) [from 3.9 (3.5, 4.8) to 6.2 (4.6, 26.2) ms/mmHg, P<0.05]. Increases in the slope of BRS persisted following withdrawal of CPAP [4.9 (4.3, 6.9) ms/mmHg, P<0.05]. CPAP also lowered heart rate (from 81.3 +/- 4.9 to 76.0 +/- 5.7 bpm, P< 0.05), an effect which persisted after its withdrawal (76.7 +/- 5.7 bpm, P < 0.05). Systolic blood pressure at the midpoint of the pressure range of BRS sequences fell while on CPAP (from 139 +/- 8 to 120 +/- 7 mmHg, P < 0.05), and remained lower following CPAP withdrawal (124 +/- 9 mmHg, P < 0.05). CONCLUSIONS: In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.

High prevalence of unrecognized sleep apnoea in drug-resistant hypertension.

OBJECTIVES: To determine the prevalence of obstructive sleep apnoea (OSA) in adult patients with drug-resistant hypertension, a common problem in a tertiary care facility. DESIGN: Cross-sectional study. SETTING: University hypertension clinic. PATIENTS AND METHODS: Adults with drug-resistant hypertension, defined as a clinic blood pressure of > or = 140/90 mmHg, while taking a sensible combination of three or more antihypertensive drugs, titrated to maximally recommended doses. Each of the 41 participants completed an overnight polysomnographic study and all but two had a 24 h ambulatory blood pressure measurement. RESULTS: Prevalence of OSA, defined as an apnoea-hypopnoea index of > or = 10 obstructive events per hour of sleep, was 83% in the 24 men and 17 women studied. Patients were generally late middle-aged (57.2 +/- 1.6 years, mean +/- SE), predominantly white (85%), obese (body mass index, 34.0 +/- 0.9 kg/m2) and taking a mean of 3.6 +/- 0.1 different antihypertensive medications daily. OSA was more prevalent in men than in women (96 versus 65%, P = 0.014) and more severe (mean apnoea-hypopnoea index of 32.2 +/- 4.5 versus 14.0 +/- 3.1 events/h, P = 0.004). There was no gender difference in body mass index or age. Women with OSA were significantly older and had a higher systolic blood pressure, lower diastolic blood pressure, wider pulse pressure and slower heart rate than women without OSA. CONCLUSIONS: The extraordinarily high prevalence of OSA in these patients supports its potential role in the pathogenesis of drug-resistant hypertension, and justifies the undertaking of a randomized controlled trial to corroborate this hypothesis.