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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complex nature of interactions between the pulmonary and cardiovascular systems is becoming increasingly appreciated. Pulmonary vascular abnormalities are frequently present in patients with respiratory disorders, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, sarcoidosis, neuromuscular or chest wall disorders, and disorders of ventilatory control including sleep apnea syndromes and obesity hypoventilation syndrome. Pulmonary hypertension, classified as group III in the World Health Organization classification scheme for pulmonary hypertension, may result in severe right ventricular dysfunction caused by lung disease, also known as cor pulmonale. The development of cor pulmonale is generally associated with poorer prognosis and increased death. Systemic manifestations of lung disease, particularly obstructive disorders, are also particularly relevant because they are associated with increased cardiac death and impaired health status. This article will discuss the most common pulmonary diseases and disorders of ventilatory control that cause pulmonary vascular abnormalities and cor pulmonale, with particular concentration on how treatment of these diseases may affect the heart. In addition, the complex nature of cardiac and lung disease will also be explored, particularly with respect to the relationship between chronic obstructive pulmonary disease, systemic inflammation, atherosclerosis, and cardiovascular death, which is currently a very active focus of research.
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PMID:Pulmonary diseases and the heart. 1808 41

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B(4) is a lipid mediator involved in atherogenesis. In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB(4) production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB(4) production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB(4) production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB(4) production, which was measured by liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls. LTB(4) production was increased in OSA patients compared with controls. LTB(4) levels correlated with the mean and minimal arterial oxygen saturation (S(a,O(2))). LTB(4) production correlated with luminal diameter data in patients with a mean S(a,O(2)) of < or = 94% but not with IMT. Lastly, CPAP significantly reduced LTB(4) production by 50%. Leukotriene B(4) production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B(4) could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
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PMID:Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea? 1832 35

Obstructive sleep apnea (OSA), a highly prevalent breathing disorder in sleep, characterized by intermittent and recurrent pauses in respiration, has emerged as an independent risk factor for cardiovascular morbidity and mortality. Accumulated evidence implicates Leukocyte-endothelial cell activation and adhesion as critical components that induce inflammation and injury to the vasculature resulting in the development of cardiovascular complications. Similar cellular interactions were described in conditions of ischemia/reperfusion, and various components of the metabolic syndrome as hypercholesterolemia and hypertension. The hallmark of sleep apnea--the multiple cycles of hypoxia/reoxygenation--promote oxidative stress and inflammation. These facilitate increased interactions of blood cells with endothelial cells, resulting in endothelial cell injury and dysfunction. Such events can promote atherosclerosis and the development of cardiovascular morbidities in OSA. However, inter-individual differences in response to intermittent hypoxia and activation of anti-inflammatory cytokine profiles in T lymphocytes can serve as protective mechanisms.
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PMID:Biology of peripheral blood cells in obstructive sleep apnea--the tip of the iceberg. 1894 85

Although sleep apnea is closely associated with cardiovascular disease, it remains underdiagnosed and undertreated. Obstructive sleep apnea elicits a cascade of harmful cardiovascular stimuli, and central sleep apnea is a prognostic factor for heart failure and may exert adverse effects on outcomes. The adverse effects of obstructive sleep apnea can promote the development of atherosclerosis and have also been implicated in the pathogenesis of cardiovascular disease. Sleep apnea characterized by variables of the autonomic nervous system may have a direct association with arrhythmia. Polysomnography with electroencephalography is the gold standard for assessing sleep apnea. Alternative methods of screening for OSA have recently become available. Continuous positive airway pressure for obstructive sleep apnea reduces cardiac risk and cardiovascular disease mortality. Targeting sleep apnea in the primary and/or secondary prevention of cardiovascular disease may lead to better outcomes.
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PMID:Sleep apnea and the heart: diagnosis and treatment. 1895 75

Moderate-severe obstructive sleep apnoea (OSA) has been associated with several pro-atherogenic mechanisms and increased cardiovascular risk, but it is not known if minimally symptomatic OSA has similar effects. Circulating cell-derived microparticles have been shown to have pro-inflammatory, pro-coagulant and endothelial function-impairing effects, as well as to predict subclinical atherosclerosis and cardiovascular risk. In 57 patients with minimally symptomatic OSA, and 15 closely matched control subjects without OSA, AnnexinV-positive, platelet-, leukocyte- and endothelial cell-derived microparticles were measured by flow cytometry. In patients with OSA, median (interquartile range) levels of AnnexinV-positive microparticles were significantly elevated compared with control subjects: 2,586 (1,566-3,964) microL(-1) versus 1,206 (474-2,501) microL(-1), respectively. Levels of platelet-derived and leukocyte-derived microparticles were also significantly higher in patients with OSA (2,267 (1,102-3,592) microL(-1) and 20 (14-31) microL(-1), respectively) compared with control subjects (925 (328-2,068) microL(-1) and 15 (5-23) microL(-1), respectively). Endothelial cell-derived microparticle levels were similar in patients with OSA compared with control subjects (13 (8-25) microL(-1) versus 11 (6-17) microL(-1)). In patients with minimally symptomatic obstructive sleep apnoea, levels of AnnexinV-positive, platelet- and leukocyte-derived microparticles are elevated when compared with closely matched control subjects without obstructive sleep apnoea. These findings suggest that these patients may be at increased cardiovascular risk, despite being minimally symptomatic.
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PMID:Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea. 1904 14

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.
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PMID:Sleep in heart failure. 1911 Jan 35

Obstructive sleep apnea (OSA) affects 25% of the Western adult population. It is an independent but seldom-recognized risk factor for hypertension, myocardial infarction, stroke, and increased mortality. Patients with OSA experience repetitive episodes of hypoxia/reoxygenation during transient cessation of breathing that promote systemic oxidative stress and inflammation. Vascular endothelial inflammation and enhanced oxidative stress that are reversible with therapy for OSA were recently demonstrated directly in patients with OSA who were free of overt cardiovascular conditions. Vascular endothelial inflammation and enhanced oxidative stress may in part explain the accelerated progression of atherosclerosis in patients with untreated OSA. The present review will focus on indirect and direct evidence of vascular endothelial inflammation and enhanced oxidative stress in patients with OSA. The potential utility of venous endothelial biopsy technique in evaluating the mechanisms that mediate the effects of systemic conditions such as diabetes mellitus, sleep apnea, and obesity on the vascular endothelium will also be discussed.
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PMID:Inflammation, oxidative stress, and the vascular endothelium in obstructive sleep apnea. 1923 54

Obstructive sleep apnea (OSA) is associated with significant cardiovascular morbidity and excess in mortality. Atherosclerosis has been shown to occur in OSA patients free of any other significant risk factors. In particular, intima media thickness, an early marker of atherosclerosis, may be increased at the carotid level in OSA. Thus, early atherosclerosis could be one of the intermediary mechanisms supporting the link between OSA and cardiovascular morbidity. The current concept is that the development of atherosclerotic lesions results from a dynamic interplay between the native cells of the vasculature and different proinflammatory leukocytes issued from the general circulation. Immunoinflammatory cells dominate early atherosclerotic processes, with the secretion of several proinflammatory molecules aggravating lesion progression. There is now substantial evidence that intermittent hypoxia in rodents, as a partial model of sleep apnea, triggers atherogenesis. Blood pressure alterations and hemodynamic strains on the vascular wall, impairment in vascular reactivity, lipid metabolism dysregulation, and activation of proinflammatory transcription factors at the vascular wall level are among the key factors promoting atherosclerosis. Specifically, increases in leukocyte rolling and adhesion molecule expression at the endothelial cell level have been shown to occur in the first 2 weeks after intermittent hypoxia exposure initiation. Early changes at the vascular wall level have been shown in OSA patients and its reversibility under continuous positive airway pressure has also been suggested. Several biological markers potentially linked with early atherosclerosis development are under study in OSA patients. Further studies are needed to identify at-risk subjects prone to develop vascular changes because OSA treatment may either be initiated earlier or combined with specific drug treatments.
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PMID:Obstructive sleep apnea and atherosclerosis. 1924 46

Data from animal and human studies provide a biological plausibility to the notion that obstructive sleep apnea activates pathways that lead to insulin resistance, atherosclerosis and hypertension. Sleep apnea thus activates the same pathways as does obesity. That obstructive sleep apnea is a risk factor for cardiovascular disease is supported by epidemiological association studies. Longitudinal cohort studies also provide evidence that patients with untreated severe sleep apnea have an increased rate of cardiovascular events. But these studies, while highly suggestive, do not provide the evidence needed to convince the skeptic. This would only be obtained by randomized treatment trials with hard cardiovascular endpoints such as cardiac events and deaths. While such studies are in the planning stages, they will be challenging. There are issues about randomizing individuals with severe sleep apnea and excessive sleepiness into no therapy, since they are at known increased risk for car crashes. Thus, lack of therapy puts others on the road at risk as well as the subject with sleep apnea. There is, moreover, the concern that treating obstructive sleep apnea in very obese individuals will have little impact, since any effect of therapy for OSA will be overwhelmed by the effects of obesity itself. Data from randomized treatment trials for cardiovascular endpoints will likely not be available for many years. In the interim, physicians need to consider how to treat such patients. It is proposed that given that CPAP treatment for obstructive sleep apnea is highly effective and essentially totally safe, and that the evidence is suggestive that sleep apnea is a risk factor for cardiovascular disease, then we propose all patients with severe sleep apnea should be treated to reduce cardiovascular risk.
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PMID:Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. 1924 49

Sleep-disordered breathing, and particularly the highly prevalent obstructive sleep apnea syndrome, is a multicomponent disorder combining intermittent hypoxia (IH), sleep fragmentation, and obstructed respiratory efforts. It is frequently associated with comorbidities and leads to numerous complications, including cardiovascular consequences that are conditioned by genetic predisposition and environment. The complexity of the disease and the reduced possibilities for patient investigations, especially at the tissue level, have limited progress in the understanding of sleep apnea pathophysiology and in the development of specific treatments. Animal models make it possible to study the causative mechanisms (essentially upper airway dysfunction) and the consequences (cardiovascular, metabolic, and neurological alterations) of nocturnal respiratory events without the confounding factors that occur in humans. Such studies have revealed some of the pathophysiological mechanisms and enabled the recognition of IH as the most important sleep apnea component underlying cardiovascular complications. We review different animal models used to assess detrimental sleep apnea-related cardiovascular consequences: blood pressure elevation, impaired vasoreactivity, structural arterial remodeling leading to atherosclerosis, cardiac remodeling, and myocardial infarction. We also review experimental evidence of beneficial effects of IH. By combining clinical and experimental research, these models will contribute to the understanding of differential patient susceptibility and to the elaboration of prevention strategies and tailored treatments for sleep apnea patients.
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PMID:Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease. 1950 13


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