Cardiovascular Consequences Of Obstructive Sleep Apnea Research Articles

Severe Obstructive Sleep Apnea Disrupts Vigilance-State-Dependent Metabolism.

The direct pathophysiological effects of obstructive sleep apnea (OSA) have been well described. However, the systemic and metabolic consequences of OSA are less well understood. The aim of this secondary analysis was to translate recent findings in healthy subjects on vigilance-state-dependent metabolism into the context of OSA patients and answer the question of how symptomatic OSA influences metabolism and whether these changes might explain metabolic and cardiovascular consequences of OSA. Patients with suspected OSA were assigned according to their oxygen desaturation index (ODI) and Epworth Sleepiness Scale (ESS) score into symptomatic OSA and controls. Vigilance-state-dependent breath metabolites assessed by high-resolution mass spectrometry were used to test for a difference in both groups. In total, 44 patients were eligible, of whom 18 (40.9%) were assigned to the symptomatic OSA group. Symptomatic OSA patients with a median [25%, 75% quartiles] ODI of 40.5 [35.0, 58.8] events/h and an ESS of 14.0 [11.2, 15.8] showed moderate to strong evidence for differences in 18 vigilance-state-dependent breath compounds compared to controls. These identified metabolites are part of major metabolic pathways in carbohydrate, amino acid, and lipid metabolism. Thus, beyond hypoxia per se, we hypothesize that disturbed sleep in OSA patients persists as disturbed sleep-dependent metabolite levels during daytime.

Establishment of a Rabbit Model of Chronic Obstructive Sleep Apnea and Application in Cardiovascular Consequences.

Background:Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress.Methods:The rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography.Results:After 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2 showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-α increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264.75 ± 25.54 pg/ml, respectively, both P < 0.001). Compared with the sham and the control groups, myocardial activities of Na+-K+-ATPase/Ca2+-ATPase and SOD in the obstruction group decreased markedly, while ROS and MDA content increased.Conclusions:These results show that the rabbit model for OSA simulates the pathophysiological characteristics of OSA in humans, which implies that this animal model is feasible and useful to study the mechanisms involved in the cardiovascular consequences of OSA.

Obstructive Sleep Apnea and Cardiovascular Disease - A New Target for Treatment.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) in breathing during sleep due to airway collapse in the oral or pharyngeal region. Prospective studies have established the adverse cardiovascular consequences of OSA, including an increased risk for developing hypertension, coronary artery disease, stroke, and heart failure. However, more studies are needed to better assess the impact of OSA, and possible benefit of treatment with continuous positive airway pressure (CPAP) on cardiovascular mortality. The leading pathophysiological mechanisms involved in the changes triggered by OSA include intermittent hypoxemia and re-oxygenation, arousals and changes in intrathoracic pressure. Hypertension is strongly related with activation of the sympathetic nervous system, stimulation of the renin-angiotensin-aldosterone system and endothelial dysfunction. OSA should be suspected in hypertensive individuals, particularly in patients with resistant hypertension. CPAP treatment reduces blood pressure, and its effects are more pronounced in patients with high baseline blood pressure and elevated treatment compliance. At present, no clear evidence supports CPAP treatment for primary or secondary cardiovascular disease prevention.

Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction, and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant pathophysiological disturbance in OSA-intermittent hypoxia. Despite several limitations in translating data from animal models to the clinical arena, significant progress has been made in our understanding of how OSA confers increased cardiovascular risk. It is clear now that the hypoxic stress associated with OSA can elicit a broad spectrum of pathological systemic events including sympathetic activation, systemic inflammation, impaired glucose and lipid metabolism, and endothelial dysfunction, among others. This review provides an update of the basic, clinical, and translational advances in our understanding of the metabolic dysfunction and cardiovascular consequences of OSA and highlights the most recent findings and perspectives in the field.

Pharmacologic approaches for the management of symptoms and cardiovascular consequences of obstructive sleep apnea in adults

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia, arousals from sleep, and daytime sleepiness. Accumulating evidence indicates that hypoxemia and sleep disruption contribute to the development of cardiovascular abnormalities in OSA. OSA is effectively treated with continuous positive airway pressure (CPAP) therapy that splints open the airway during sleep. Studies have shown that CPAP therapy improves daytime sleepiness and attenuates cardiovascular abnormalities in patients with OSA. However, not all patients with OSA tolerate or adhere to CPAP therapy. Even patients who regularly use CPAP therapy may have a few hours each night exposed to the negative effects of untreated OSA. As a result, complementary pharmacologic therapies that can be used with CPAP therapy have the potential to reduce symptoms and consequences of OSA. The wake-promoting medications modafinil and armodafinil effectively improve residual sleepiness in patients treated with CPAP therapy. Although results are equivocal so far, modafinil and armodafinil may also improve quality of life and global clinical condition in patients with OSA and residual sleepiness treated with CPAP therapy. Pharmacologic therapies also have the potential to be used with CPAP therapy to minimize cardiovascular perturbations and risk of cardiovascular disease. Preliminary studies suggest that inhibition of the enzyme xanthine oxidase and inhibition of sympathetic nervous system overactivity may have therapeutic potential to reduce cardiovascular harm in patients with OSA. Future studies of pharmacologic therapies to reduce symptoms and cardiovascular consequences of OSA should be increasingly performed as our understanding of the mechanisms mediating the adverse effects of OSA continues to evolve.

Cardiovascular consequences of sleep apnea: III-Impact of continuous positive airway pressure treatment

Obstructive sleep apnea (OSA) is a common condition in patients with cardiovascular diseases (CVD). The first line treatment of OSA is continuous positive airway pressure (CPAP), which reduces daytime sleepiness and improves quality of life in sleep-clinic based populations. However, in the cardiac populations, the majority of OSA subjects do not report daytime sleepiness. To date, there is not enough evidence to draw the conclusion that all CVD patients should be investigated for OSA and subsequently be treated with CPAP. The current article focuses on the available research evidence addressing the impact of CPAP on the cardiovascular consequences of OSA in both clinic- and population-based cohorts.

Rat Model of Chronic Recurrent Airway Obstructions to Study the Sleep Apnea Syndrome

To implement a chronic rat model of recurrent airway obstructions to study the obstructive sleep apnea (OSA) syndrome. Prospective controlled animal study. University laboratory. 24 male Sprague-Dawley rats (250-300 g). The rats were placed in a setup consisting of a body chamber and a head chamber separated by a neck collar specially designed to apply recurrent airway obstructions with OSA patterns. Rats in the Obstruction group (n=8) were subjected to 5-s obstructions at a rate of 60 per hour, 6 h/day during 4 weeks. Sham rats (n=8) were placed in the setup but no obstructions were applied. Naive rats (n=8) were subjected to no intervention. Breathing flow, pressure, CO2 air concentration, and SpO2 showed that the model mimicked OSA respiratory events (obstructive apneas, increased respiratory efforts, and oxygen saturation dips). Animal stress, assessed by body weight and plasma corticosterone, was not significantly different across Obstruction and Sham groups. This supports the concept that this novel model does not introduce a significant burden of stress in the rat after acclimatization to the chamber. Thromboxane-B2/6-keto-Prostaglandin-Flalpha ratio in plasma, which is an index of vasoconstriction, was significantly increased in the rats subjected to obstructions. The designed animal model of chronic recurrent airway obstructions is feasible and potentially useful to study the mechanisms involved in the cardiovascular consequences of OSA.

Sleep apnea in renal patients.

In Western societies, sleep apnea (SA) has emerged as a major medical problem with important social ([1][1]) and financial implications. The issue may be even more relevant in nephrology because some of the factors involved in the pathogenesis of renal disease are the same that cause, or are