Owen D. Lyons

Sleep Apnea and Stroke

Stroke is the second leading cause of death worldwide and often has devastating consequences for affected individuals in terms of chronic disability. Traditional risk factors such as age, male sex, ethnicity, hypertension, and atrial fibrillation explain 60%-80% of the risk of stroke. Obstructive sleep apnea (OSA) is highly prevalent in individuals who have had a stroke and its emerging role as a potential modifiable risk factor for stroke has been recognized in the most recent American Heart Association stroke guidelines, which recommend consideration of screening for and treatment of OSA in this regard. In this article we provide an overview of the current evidence-based knowledge related to stroke and sleep apnea. The main focus of this article is key pathophysiological mechanisms by which OSA might increase the risk for stroke. The effect of OSA on stroke outcomes and the efficacy of treatment of OSA on these outcomes is also discussed.

Effect of Ultrafiltration on Sleep Apnea and Sleep Structure in Patients with End-Stage Renal Disease

RATIONALE In end-stage renal disease (ESRD), a condition characterized by fluid overload, both obstructive and central sleep apnea (OSA and CSA) are common. This observation suggests that fluid overload is involved in the pathogenesis of OSA and CSA in this condition. OBJECTIVES To test the hypothesis that fluid removal by ultrafiltration (UF) will reduce severity of OSA and CSA in patients with ESRD. METHODS At baseline, on a nondialysis day, patients with ESRD on thrice-weekly hemodialysis underwent overnight polysomnography along with measurement of total body extracellular fluid volume (ECFV), and ECFV of the neck, thorax, and right leg before and after sleep. The following week, on a nondialysis day, subjects with an apnea-hypopnea index (AHI) greater than or equal to 20 had fluid removed by UF, followed by repeat overnight polysomnography with fluid measurements. MEASUREMENTS AND MAIN RESULTS Fifteen patients (10 men) with an AHI greater than or equal to 20 (10 OSA; 5 CSA) participated. Mean age was 53.5 ± 10.4 years and mean body mass index was 25.3 ± 4.8 kg/m(2). Following removal of 2.17 ± 0.45 L by UF, the AHI decreased by 36% (43.8 ± 20.3 to 28.0 ± 17.7; P < 0.001) without affecting uremia. The reduction in AHI correlated with the reduction in total body ECFV (r = 0.567; P = 0.027) and was associated with reductions in ECFV of the right leg (P = 0.001), overnight change in ECFV of the right leg (P = 0.044), ECFV of the thorax (P = 0.001), and ECFV of the neck (P = 0.003). CONCLUSIONS These findings indicate that fluid overload contributes to the pathogenesis of OSA and CSA in ESRD, and that fluid removal by UF attenuates sleep apnea without altering uremic status.

Heart Failure and Sleep Apnea

Obstructive and central sleep apnea are far more common in heart failure patients than in the general population and their presence might contribute to the progression of heart failure by exposing the heart to intermittent hypoxia, increased preload and afterload, sympathetic nervous system activation, and vascular endothelial dysfunction. There is now substantial evidence that supports a role for fluid overload and nocturnal rostral fluid shift from the legs as unifying mechanisms in the pathogenesis of obstructive and central sleep apnea in heart failure patients, such that the predominant type of sleep apnea is related to the relative distribution of fluid from the leg to the neck and chest. Despite advances in therapies for heart failure, mortality rates remain high. Accordingly, the identification and treatment of sleep apnea in patients with heart failure might offer a novel therapeutic target to modulate this increased risk. In heart failure patients with obstructive or central sleep apnea, continuous positive airway pressure has been shown to improve cardiovascular function in short-term trials but this has not translated to improved mortality or reduced hospital admissions in long-term randomized trials. Other forms of positive airway pressure such as adaptive servoventilation have shown promising results in terms of attenuation of sleep apnea and improvement in cardiovascular function in short-term trials. Large scale, randomized trials are required to determine whether treating sleep apnea with various interventions can reduce morbidity and mortality.

Effects of exercise training on sleep apnoea in patients with coronary artery disease: a randomised trial.

Overnight fluid shift from the legs to the neck and lungs may contribute to the pathogenesis of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA). We hypothesised that exercise training will decrease the severity of OSA and CSA in patients with coronary artery disease (CAD) by decreasing daytime leg fluid accumulation and overnight rostral fluid shift. Patients with CAD and OSA or CSA (apnoea–hypopnoea index >15 events per h) were randomised to 4 weeks of aerobic exercise training or to a control group. Polysomnography, with measurement of leg, thoracic and neck fluid volumes and upper-airway cross-sectional area (UA-XSA) before and after sleep, was performed at baseline and follow-up. 17 patients per group completed the study. Apnoea–hypopnoea index decreased significantly more in the exercise group than in the control group (31.1±12.9 to 20.5±9.4 versus 28.1±13.5 to 27.0±15.1 events per h, p=0.047), in association with a greater reduction in the overnight change in leg fluid volume (579±222 to 466±163 versus 453±164 to 434±141 mL, p=0.04) and by a significantly greater increase in the overnight change in UA-XSA in the exercise group (p=0.04). In patients with CAD and sleep apnoea, exercise training decreases sleep apnoea severity via attenuation of overnight fluid shift and an increase in UA-XSA. In patients with CAD and moderate-to-severe sleep apnoea, exercise training reduces AHI during sleep http://ow.ly/YvQzS

Design of the effect of adaptive servo-ventilation on survival and cardiovascular hospital admissions in patients with heart failure and sleep apnoea: the ADVENT-HF trial

Both types of sleep‐disordered breathing (SDB), obstructive and central sleep apnoea (OSA and CSA, respectively), are common in patients with heart failure and reduced ejection fraction (HFrEF). In such patients, SDB is associated with increased cardiovascular morbidity and mortality but it remains uncertain whether treating SDB by adaptive servo‐ventilation (ASV) in such patients reduces morbidity and mortality.

Effect of below-the-knee compression stockings on severity of obstructive sleep apnea

BACKGROUND Overnight fluid shift from the legs to the neck may narrow the upper airway and contribute to obstructive sleep apnea (OSA) pathogenesis. We hypothesized that below-the-knee compression stockings will decrease OSA severity in a general OSA population by decreasing daytime leg fluid accumulation and overnight fluid shift and increasing upper-airway size. METHODS Patients with OSA (apnea-hypopnea index ≥ 10) were randomized to wear compression stockings during the daytime or to a control group for 2 weeks. Overnight polysomnography with measurement of leg and neck fluid volumes and upper-airway cross-sectional area before and after sleep was performed at baseline and follow-up. The primary outcome was change in the apnea-hypopnea index. RESULTS Twenty-two patients randomized to compression stockings and 23 to control completed the study. The apnea-hypopnea index decreased significantly more in the compression stockings than in the control group (from 32.4 ± 20.0 to 23.8 ± 15.5 vs. from 31.2 ± 25.0 to 30.3 ± 23.8, p = 0.042), in association with a significantly greater reduction in the overnight decrease in leg fluid volume (p = 0.028), and a significantly greater increase in morning upper-airway cross-sectional area (p = 0.006). Overnight change in neck fluid volume was unchanged. CONCLUSION These observations suggest that in, a general OSA population, below-the-knee compression stockings decrease OSA severity modestly via attenuation of overnight fluid shift and consequent upper-airway dilatation.

Night-to-night variability in obstructive sleep apnea severity: relationship to overnight rostral fluid shift.

STUDY OBJECTIVES Overnight rostral fluid shift from the legs to the neck may narrow the pharynx and contribute to obstructive sleep apnea (OSA) pathogenesis. We hypothesized that night-to-night changes in the apnea-hypopnea index (AHI) would be associated with changes in overnight rostral fluid shift. METHODS Twenty-six patients with OSA (AHI ≥10) underwent two polysomnograms 14 days apart with measurement of neck and leg fluid volumes (LFV), neck circumference and upper-airway cross-sectional area before and after sleep. RESULTS Although mean AHI did not differ between polysomnograms, 35% of patients had a difference in AHI >10, indicating significant intra-individual variability. There were direct correlations between change in non-rapid-eye movement (NREM), but not REM AHI and change in evening LFV between polysomnograms (r = 0.440, p = 0.036 and r = 0.005, p = 0.982, respectively) and between change in supine, but not non-supine AHI and change in evening LFV (r = 0.483, p = 0.020 and r = 0.269, p = 0.280, respectively). An increase in evening LFV between polysomnograms was associated with a greater overnight decrease in LFV (r = 0.560, p = 0.005) and a greater overnight increase in neck fluid volume (r = 0.498, p = 0.016). Additionally, a greater overnight increase in neck circumference was associated with a greater overnight increase in neck fluid volume between polysomnograms (r = 0.453, p = 0.020) and a greater overnight decrease in upper-airway cross-sectional area (r = -0.587, p = 0.005). CONCLUSION Intra-individual variability in OSA severity may be partly explained by day-to-day changes in evening leg fluid volume and overnight rostral fluid shift, which may be most important in the pathogenesis of OSA during NREM and supine sleep.

Hypervolemia and Sleep Apnea in Kidney Disease

In end-stage renal disease (ESRD) and heart failure, conditions characterized by fluid overload, both obstructive sleep apnea (OSA) and central sleep apnea (CSA) are highly prevalent. This observation suggests that fluid overload may be a unifying mechanism in the pathogenesis of both OSA and CSA in these conditions. An overnight rostral fluid shift from the legs to the neck and lungs has been shown to contribute to the pathogenesis of OSA and CSA, respectively, in various different patient populations. This article reviews the evidence that supports a role for fluid overload and overnight fluid shift in the pathogenesis of sleep apnea in ESRD. The diagnosis, epidemiology, and clinical features of sleep apnea in patients with ESRD also are considered.

Relationship of left atrial size to obstructive sleep apnea severity in end-stage renal disease

BACKGROUND Increased left atrial (LA) size is linked to elevated mortality in end-stage renal disease (ESRD). In addition, the degree of overnight rostral fluid shift from the legs is associated with severity of obstructive sleep apnea (OSA). As rostral fluid shift might distend the left atrium and increase fluid accumulation in the neck, we postulated that LA size would be related to the degree of overnight rostral fluid shift and OSA severity in ESRD patients. METHODS Patients with ESRD underwent echocardiography and polysomnography. Leg fluid volume (LFV) was measured by bioelectrical impedance before and after the overnight sleep study in a subset of 21 patients. RESULTS Forty patients (22 men), with a mean apnea-hypopnea index (AHI) of 25.1 ± 23.4/h of sleep, had echocardiography and polysomnography performed. In men, there was a correlation between the AHI and LA size indexed for body surface area (r = 0.743, p < 0.001) that was not observed in women. Strong relationships were seen, again in men only, between LA size indexed to body surface area and the overnight change in leg fluid volume (ΔLFV) (r = -0.739, p = 0.02) and between AHI and ΔLFV (r = -0.863, p = 0.003). CONCLUSIONS In ESRD patients, there are relationships between ΔLFV and both LA size and OSA severity. These findings suggest that the relationship between LA size and mortality in ESRD may be related to ΔLFV and severity of OSA.

The effect of sitting and calf activity on leg fluid and snoring

Prolonged sitting may promote leg fluid retention that redistributes to the neck during sleep and contributes to snoring. This could be attenuated by calf activity while sitting. In 16 healthy non-obese subjects we measured leg fluid volume (LFV) below the knees using bioelectrical impedance while sitting for 4h, snoring using a portable BresoDx™ device, and Mallampati grade. Using a double cross-over study design, subjects were randomized to one of two arms and crossed-over one week later: control arm - no calf exercise while sitting; intervention arm - calf contraction against a pedal resistance while sitting. The effects of sitting±calf activity on LFV and snoring were compared. We found that LFV increased by 216±101.0ml (p<0.0001) after sitting. Calf activity while sitting attenuated LFV by 53.8ml (p<0.0001) and, in all five subjects with severe upper airway narrowing (Mallampati grade IV), reduced snoring duration (from 357±132.9 to 116.2±72.1s/h, p=0.02) suggesting reduced overnight rostral fluid shift to the neck.