Francoise Roux

Sleep-related breathing disorders and cardiovascular disease

Sleep-related breathing disorders, ranging from habitual snoring to the increased upper airway resistance syndrome to sleep apnea, are now recognized as major health problems. The majority of patients have excessive daytime sleepiness and tiredness. Neuropsychological dysfunction results in poor work performance, memory impairment, and even depression. Until recently, the coexistence of cardiovascular and cerebrovascular diseases with sleep-related breathing disorders was thought to be the result of shared risk factors, such as age, sex, and obesity. However, in the past 5 years several epidemiologic studies have demonstrated that sleep-related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic tone, and altered baroreflex control during sleep. Sleep apnea may lead to the development of cardiomyopathy and pulmonary hypertension. Early recognition and treatment of sleep-related breathing disorders may improve cardiovascular function.

Impaired cerebral autoregulation in obstructive sleep apnea

Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.

Continuous Positive Airway Pressure: evaluation of a Novel Therapy for Patients with Acute Ischemic Stroke

BACKGROUND New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity. METHODS Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days. RESULTS The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and intervention patients. Intervention patients had greater improvements in NIHSS (-3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: -1.0 for control patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP use; and -3.0 for intervention patients with acceptable auto-CPAP adherence. CONCLUSIONS The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

The relationship of obesity and obstructive sleep apnea.

Obstructive sleep apnea is a common disorder, and obesity is a known risk factor for its development. The prevalence of obesity is increasing worldwide, and a corresponding increase in the prevalence of obstructive sleep apnea and its cardiovascular and noncardiovascular consequences is likely. This article reviews the established evidence supporting obesity as a risk factor for obstructive sleep apnea and discusses the evidence suggesting that obesity is also a consequence of obstructive sleep apnea. There is evidence that treating obesity reduces the severity of obstructive sleep apnea and that treating obstructive sleep apnea decreases obesity. However, the evidence does not support a sustained correlation between weight loss and improvement in sleep-disordered breathing.

Auto-Titrating Continuous Positive Airway Pressure for Patients With Acute Transient Ischemic Attack A Randomized Feasibility Trial

Background and Purpose— Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. Methods— All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as ≥4 hours per night for ≥75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. Results— We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%; P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%; some, 5%; acceptable adherence 0% (P=0.08). Conclusions— Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.

Medication Effects on Sleep

The understanding of the neuropharmacologic reciprocal interactions between the sleep and wake cycles has progressed significantly in the past decade. It was also recently appreciated that sleep disruption or deprivation can have adverse metabolic consequences. Multiple medications have a direct or indirect impact on sleep and the waking state. This article reviews how commonly prescribed medications can significantly affect the sleep-wake cycle.

Continuous positive airway pressure: new generations.

Automatic positive airway pressure devices are the most technologically advanced positive airway pressure devices available for use in OSA. Although heterogeneous, they have in common the ability to detect and respond to changes in upper airway resistance. Data cannot necessarily be extrapolated from one device to another, and the field is rapidly advancing. Most studies of APAP have been performed in a supervised setting, or patients have been carefully selected to have a high likelihood of OSA uncomplicated by disorders such as alveolar hypoventilation or central apnea or technical problems such as mask leaks. Studies of APAP for the diagnosis of OSA have shown that APAP can diagnose severe OSA effectively, but the diagnosis of mild-moderate OSA is less reliable. APAP devices also can be effective therapy for selected patients with OSA, with overall similar results to conventional fixed CPAP in terms of respiratory disturbances, sleep quality, nocturnal oxygenation, and daytime sleepiness and performance, with less known or other long-term outcomes. In most studies, mean treatment pressures are lower, without change in side effect profile. Compliance and preference with APAP are similar to or somewhat better than CPAP in most studies. APAP also can be used in an attended setting to titrate an effective pressure for use in long-term conventional CPAP therapy, also with similar results to CPAP in many patients. APAP devices are more expensive than CPAP devices, but the cost may be outweighed if a group of patients who can be diagnosed, treated, or titrated safely in the unattended setting can be identified. Although diagnostic and therapeutic algorithms for APAP have been proposed, the best candidates for this modality must be defined better.

Restless legs syndrome: impact on sleep-related breathing disorders.

Restless legs syndrome (RLS) is a common chronic sensory‐motor neurological disorder that remains a clinical diagnosis. Most RLS patients present with sleep complaints in the form of initiation and/or maintenance insomnia as RLS has a circadian rhythmicity. An increased number of periodic leg movements during sleep (PLMS) is a supportive criterion in the diagnosis of RLS. Abnormalities in the central dopaminergic and iron systems are involved in the physiopathology of RLS. There is a higher prevalence of RLS and PLMS in sleep‐disordered breathing patients, particularly those with obstructive sleep apnoea (OSA), the most common sleep disorder in western societies. The complex mechanisms underlying the association between OSA, RLS and PLMS remain unclear. Untreated OSA can lead to adverse cardiovascular consequences due to cardio‐metabolic dysfunction. It remains controversial whether RLS could further adversely impact the cardiovascular consequences of OSA. The PLMS do not have an additive effect on the hypersomnia experienced by some sleep‐disordered breathing patients. Continuous positive airway pressure (CPAP) therapy is the most effective therapy for OSA. The presence of PLMS during CPAP treatment could be a marker of an incomplete resolution of sleep‐disordered breathing in the form of increased upper airway resistance syndrome, despite treatment. Dopaminergic agonists are the preferred agent for the treatment of RLS, and are indicated when RLS symptoms are frequent and affect quality of life. PLMS and RLS do not seem to contribute to the residual hypersomnia that can be observed in some sleep‐disordered breathing patients despite adequate compliance and effective CPAP therapy.

Improving Health-Related Quality of Life in Patients with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) syndrome is a common and often life-altering sleep-related breathing disorder. It not only adversely affects cardiovascular health, but the quality of life of these patients is also often significantly compromised. They experience excessive daytime sleepiness and poor cognitive, social and exercise performance. Furthermore, they often have marital problems with increased divorce rates, depression, and poor job performance.Our purpose in writing this review is to highlight the various neuropsychiatric domains that are affected in OSA patients and to emphasize that identifying and treating this condition can significantly improve the quality of life of these individuals. In recent years there has been ample evidence supporting the role of treatment for OSA to improve cardiovascular outcomes. We provide similar evidence supporting the treatment of OSA to improve health-related quality of life outcomes for these patients. Surgical, non-surgical and pharmacologic modalities are currently available as effective options for the treatment of OSA, with continuous positive airway pressure therapy appearing to be the most promising.

Sleep and Breathing in Congestive Heart Failure

Heart failure (HF) is one of the most prevalent and costly diseases in the United States. Sleep apnea is now recognized as a common, yet underdiagnosed, comorbidity of HF. This article discusses the unique qualities that sleep apnea has when it occurs in HF and explains the underlying pathophysiology that illuminates why sleep apnea and HF frequently occur together. The authors provide an overview of the treatment options for sleep apnea in HF and discuss the relative efficacies of these treatments.