Vahid Mohsenin

Obstructive sleep apnea as a risk factor for type 2 diabetes.

PURPOSE Cross-sectional studies have documented the co-occurrence of obstructive sleep apnea (hereafter, sleep apnea) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus (hereafter, diabetes). It has not been determined, however, whether sleep apnea is independently associated with the subsequent development of diabetes, accounting for established risk factors. METHODS This observational cohort study examined 1233 consecutive patients in the Veteran Affairs Connecticut Healthcare System referred for evaluation of sleep-disordered breathing; 544 study participants were free of preexisting diabetes and completed a full, attended, diagnostic polysomnogram. The study population was divided into quartiles based on severity of sleep apnea as measured by the apnea-hypopnea index. The main outcome was incident diabetes defined as fasting glucose level >126 mg/dL and a corresponding physician diagnosis. Compliance with positive airway pressure therapy, and its impact on the main outcome, also was examined. RESULTS In unadjusted analysis, increasing severity of sleep apnea was associated with an increased risk of diabetes (P for linear trend <.001). After adjusting for age, sex, race, baseline fasting blood glucose, body mass index, and weight change, an independent association was found between sleep apnea and incident diabetes (hazard ratio per quartile 1.43; confidence interval 1.10-1.86). Among patients with more severe sleep apnea (upper 2 quartiles of severity), 60% had evidence of regular positive airway pressure use, and this treatment was associated with an attenuation of the risk of diabetes (log-rank test P=.04). CONCLUSION Sleep apnea increases the risk of developing diabetes, independent of other risk factors. Among patients with more severe sleep apnea, regular positive airway pressure use may attenuate this risk.

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.

Sleep apnea in patients with hemispheric stroke

Sleep pattern and breathing in humans are altered following cerebrovascular accidents involving the brainstem. Sleep apnea is a well-established complication of stroke involving the brainstem. On the other hand, the effect of cerebral stroke on sleep and breathing has not been well defined. The diffuse cerebral symptoms such as cognitive deficits, depression or fatigue, after hemispheric stroke mimic those present in patients with sleep apnea. To define the breathing pattern in patients with stroke involving cerebral hemispheres without brainstem lesion and without the prior history of sleep-disordered breathing, we studied 10 patients within 1 year of their stroke. The data collected during polysomnography from the stroke patients were compared with a group of subjects matched for age, body mass index, presence of hypertension, and smoking history without stroke. Patients with stroke had an abnormal sleep architecture with significantly lower slow wave sleep and rapid eye movement (REM) sleep when compared with controls. Sleep was fragmented because of the presence of increased respiratory disturbances. Stroke patients had a respiratory disturbance index of 52 +/- 10 events per hour when compared with 3 +/- 1 in controls (p < .05). Majorities of respiratory events were obstructive apneas and were associated with arterial oxygen desaturations and arousals. The pathogenic mechanism of sleep-disordered breathing in patients with hemispheric stroke seems to be related to the physiological effect of sleep on already compromised upper airway muscle control. Patients with stroke and diffuse cerebral symptoms should be investigated for the possibility of sleep-disordered breathing.

Obstructive sleep apnoea and stroke

Many patients with stroke have concomitant sleep apnoea, which can affect recovery potential. Although stroke can lead to the development of sleep-disordered breathing, the current evidence suggests that sleep-disordered breathing may function as a risk factor for stroke. In this review, we focus on the association between obstructive sleep apnoea and stroke reviewing both the epidemiological data with respect to causation and the biological data, which explores pathogenesis. There is convincing evidence to believe that sleep apnoea is a modifiable risk factor for stroke; however, prospective studies are needed to establish the cause-and-effect relationship.

Sleep-Related Breathing Disorders and Risk of Stroke

Background— Stroke and sleep-related breathing disorders are both common and are associated with significant morbidity and mortality. Several recent large epidemiological studies have shown a strong association between these 2 disorders independent of known risk factors for stroke. This article will outline the scientific basis for this relationship and suggest sleep-related breathing disorders as modifiable risk factors for stroke. Summary of Review— Several studies have shown a characteristic circadian rhythmicity in stroke. We have discussed the influence of normal sleep states as well as the effect of sleep-related breathing disorders on cerebral hemodynamics. The hemodynamic, metabolic, and hematologic changes during sleep-related breathing disorders in the form of decreased cerebral perfusion and increased coagulability are possible pathogenetic mechanisms for stroke. There are accumulating lines of evidence that sleep apnea disorder may indeed cause diurnal hypertension. However, the increased risk of stroke in patients with sleep-related breathing disorders appears to be independent of coexisting hypertension; the presence of hypertension would increase the risk even further. Furthermore, several studies have documented high prevalence of sleep apnea disorders in patients with transient ischemic attacks and stroke. Conclusions— Sleep-related breathing disorder appears to contribute as a risk factor for stroke through hemodynamic and hematologic changes. Because of the high prevalence of sleep apnea disorder in this population, patients with transient ischemic attacks and stroke should undergo evaluation for these disorders.

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.

Effects of gender on upper airway collapsibility and severity of obstructive sleep apnea

OBJECTIVE Obstructive sleep apnea (OSA) is far more common in males than females. The discrepancy between the lower prevalence of OSA, the greater frequency of obesity and the smaller airway size in women compared to men suggests that a gender difference underlies this condition. We hypothesized that due to differences in tissue linkage women have more stable and less mobile upper airway structures than men, providing protection against severe forms of OSA. METHODS Seventy-one consecutive patients with OSA, defined as having apnea-hypopnea index > or =5 events per hour, were enrolled into the study. The median (range) apnea-hypopnea index was 20 (5-132) events/h. In addition, measurements of upper airway dimensions were made, using an acoustic reflectance method, while the lower jaw was in the resting position and during retrusive posture. Measurements of upper airway dimensions were used during wakefulness to examine whether changes in pharyngeal dimensions, resulting from retrusive movement of the mandible commonly occurring during sleep, would explain the gender differences in the characteristics of OSA. RESULTS OSA was much more positional and severe in men than women as indicated by the higher apnea-hypopnea index in supine position compared with sleeping on the side (difference between supine and side apnea-hypopnea index: 43.7+/-5.2 (SEM) events/h in men versus 10.7+/-7.6 events/h in women, P=0.0015). The position dependency of OSA was most pronounced in those patients who demonstrated the largest decrease in pharyngeal cross-sectional area with retrusive movement of the mandible. There was no significant change in pharyngeal cross-sectional area as a result of retrusive movement of the mandible in women. CONCLUSIONS Men tend to have a larger but more collapsible airway during mandibular movement than women and this, in part, may play a role in the positional dependency and severity of OSA in men.

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.

Sleep-disordered Breathing in Pregnancy

Symptoms of sleep-disordered breathing are more common in pregnant women compared with nonpregnant women. It is likely that physiology of pregnancy predisposes to the development or worsening of sleep-disordered breathing, but some physiologic changes may also be protective against the development of this disease. Clinical presentation may be less predictive of sleep disordered breathing in pregnancy than in the non-pregnant population; nonetheless, snoring is associated with adverse pregnancy outcomes. Treatment strategies are similar to the nonpregnant population, however, pregnancy-specific scenarios may arise and these subtleties are addressed in this review.

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.