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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a morbid condition with hemodynamic consequences affecting the systemic and pulmonary circulations leading to a risk of pulmonary hypertension. Data in the literature do not argue in favor of a direct relationship between pulmonary hypertension and obesity. These two conditions appear to be two distinct entities, the different co-morbidities observed in obesity favoring pulmonary hypertension. Certain co-morbidities, for instance use of anorexic agents, exhibit a clear relationship with pulmonary hypertension. There is also a possible relationship with left ventricular failure, hypoxemia, and other respiratory disorders (including obstructive sleep apnea), hypothyroidism, and thomboembolism.
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PMID:[Pulmonary hypertension and obesity]. 1208 49

This study was undertaken to clarify whether pulmonary hypertension is a useful marker for underlying obstructive sleep apnea in patients with edema. Twenty-eight ambulatory adults with bilateral leg edema and a normal echocardiogram were enrolled. Sixteen subjects had pulmonary hypertension, and 12 subjects had normal pulmonary artery pressures. Spirometry, pulse oximetry on room air, and polysomnography were obtained for each subject. Ten of 16 (63%) pulmonary hypertension subjects and 9 of 12 (75%) nonpulmonary hypertension subjects had obstructive sleep apnea (P =.48). Eleven of 16 (69%) pulmonary hypertension subjects and 11 of 12 (92%) nonpulmonary hypertension subjects were obese (P =.20). If these results are generalizable, obstructive sleep apnea is frequently associated with bilateral leg edema and obesity, regardless of the presence of pulmonary hypertension. Thus, especially in obese patients, bilateral leg edema may be a useful clinical marker for underlying obstructive sleep apnea.
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PMID:Bilateral leg edema, pulmonary hypertension, and obstructive sleep apnea: a cross-sectional study. 1210 Jul 81

Sleep-related breathing disorders (SRBDs) represent a spectrum of abnormalities that range from simple snoring to upper airway resistance syndrome to sleep apnea. The clinical presentation may include obesity, snoring, neuropsychological dysfunction, and daytime hypersomnolence and tiredness. The acute hemodynamic alterations of obstructive sleep apnea include systemic and pulmonary hypertension, increased right and left ventricular afterload, and increased cardiac output. Earlier reports attributed the coexistence of SRBDs with cardiovascular diseases to the shared risk factors such as age, sex, and obesity. However, recent epidemiologic data confirm an independent association between SRBDs and the different manifestations of cardiovascular diseases. Possible mechanisms may include a combination of intermittent hypoxia and hypercapnia, repeated arousals, sustained increase in sympathetic tone, reduced baroreflex sensitivity, increased platelet aggregation, and elevated plasma fibrinogen and homocysteine levels. The strength of the association, its pathogenesis, and the impact of treatment of SRBDs on the health outcome of patients with cardiovascular diseases are issues to be addressed in future studies.
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PMID:Cardiovascular consequences of sleep-related breathing disorders. 1235 Feb 42

Anorectic drugs are widely used for the treatment of obesity. They are thought to decrease appetite through their effects on catecholamine or 5-hydroxytryptamine (5-HT) levels in the brain. Their use has been associated with epidemics of pulmonary hypertension and the development of valvular heart disease, hypertension, stroke and digital or mesenteric ischemia. Understanding the mechanism of the cardiovascular toxicity of anorectic drugs is important because of the modern epidemic of obesity and the resulting plethora of new anorexigens, many of which share similar mechanisms with those that have previously caused cardiovascular disease. In addition, the mechanism by which anorexigens cause vascular disease has relevance to the etiology and treatment of pulmonary and systemic hypertension. Recent discoveries have clarified how the anorexigens cause vasoconstriction and hypertension. Most anorexigens directly inhibit voltage-gated K+ (KV) channels in vascular smooth muscle cells (SMCs). This reduced K+ efflux leads to depolarization, the opening of voltage-sensitive Ca2+ channels, an increase in intracellular Ca2+ and vasoconstriction. Endothelial dysfunction appears to be a predisposing factor for the development of anorectic-induced vascular complications. Vasoconstriction is weak at clinically relevant doses of anorectic drugs. However, when nitric oxide synthase is inhibited, vasoconstriction is significantly enhanced. Anorexigens are the only drugs in widespread clinical use that have KV-channel-blocking properties and it is probable that much of their cardiovascular toxicity relates to this mechanism. Investigators need to examine new anorexigens and other therapeutic molecules for inhibitory effects on KV channels, as this effect may be a marker of drugs that will elicit vascular complications.
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PMID:Anorectic drugs and vascular disease: the role of voltage-gated K+ channels. 1237 23

Obesity is a chronic disorder that is associated with significant co-morbidity and early mortality. Since the 1970s, amphetamines and amphetamine analogs have been trialed for weight loss. In 1997, the anorexigen agents, fenfluramine (Pondimin; AH Robins, Richmond, VA) and dexfenfluramine (Redux; Wyeth-Ayerst, Philadelphia, PA) gained worldwide attention when reports of associated cardiac valvulopathy and pulmonary hypertension emerged. A landmark report from the Mayo Clinic describing valvular heart disease (VHD) among women exposed to the anorexigen agent combination phentermine-fenfluramine ignited widespread concern, and the products were voluntarily withdrawn from the market by the manufacturers. Currently, the causal relationship between anorexigen agent use and valvulopathy has been validated, yet the extent and complexity of this important clinical issue remains ill-defined.
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PMID:Anorexigen-induced cardiac valvulopathy and female gender. 1262 81

Obesity is associated with a chronic inflammatory state that predisposes to atherogenesis, thrombogenesis, and carcinogenesis and may increase susceptibility to infections. Critically ill, obese patients have higher mortality. MOF is the best predictor of ICU mortality for obese patients. Pulmonary hypertension and higher BMI are associated with higher surgical risk. Progress in surgical technique and anesthesia has substantially improved the safety of performing operations in severely obese patients.
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PMID:Critical care of the obese and bariatric surgical patient. 1268 75

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.
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PMID:Obstructive sleep apnea and cardiovascular disease. 1274 77

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor alpha and transforming growth factor beta), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETA and ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETA-ETB receptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.
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PMID:Role of endothelin in human hypertension. 1283 65

Dexfenfluramine, a drug formerly prescribed for treatment of obesity, caused heart valve damage and pulmonary hypertension in some people. The cause of the toxicity has not been defined, but 5-HT has been implicated. The objective of this study was to evaluate the effect of the anorectic agent, d-fenfluramine, and its major metabolite, d-norfenfluramine, on intact human platelet serotonin (5-HT) transport in vitro. The effects of d-fenfluramine and d-norfenfluramine on platelet uptake and efflux of 3H-5-HT were measured in buffer at pH 6.7, to optimize serotonin transporter (SERT) function, and at pH 7.4. Uptake of 3H-5-HT at pH 6.7 and 7.4 was inhibited by both agents at micro m concentrations (IC50, d-fenfluramine approximately 3 microM; d-norfenfluramine approximately 10 microM). However, no efflux of 3H-5-HT from labeled platelets at either pH 6.7 or 7.4 occurred at similar concentrations of d-fenfluramine or d-norfenfluramine. With inhibition of platelet dense granule 3H-5-HT uptake by reserpine, efflux of 3H-5-HT was observed at pH 6, but not at pH 7.4. Fluoxetine, a SERT inhibitor, was a more potent inhibitor of uptake (IC50 0.05 microM) than d-fenfluramine, but the anorectic agent, phentermine, had no effect. Therefore, d-fenfluramine and d-norfenfluramine inhibit human platelet uptake of 5-HT in vitro at tissue concentrations attainable in vivo, but they do not stimulate 5-HT efflux due to dense granule sequestration. Inhibition of platelet 5-HT uptake may play a role in the cardiopulmonary toxicity of d-fenfluramine, but other factors probably contribute, since similar toxicity has not been observed with fluoxetine.
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PMID:The effect of the anorectic agent, d-fenfluramine, and its primary metabolite, d-norfenfluramine, on intact human platelet serotonin uptake and efflux. 1467 3

The control of breathing in patients with chronic obstructive pulmonary disease (COPD) follows the same basic principles as in normal subjects, both awake and asleep, with an expected lower feedback response during sleep. This impacts nocturnal gas exchange and sleep quality most profoundly in patients with more severe COPD, as multiple factors come into play. Hypoventilation causes the most important gas-exchange alteration in COPD patients, leading to hypercapnia and hypoxemia, especially during rapid-eye-movement sleep, when marked respiratory muscle atonia occurs. The hypoxia leads to increased arousals, sleep disruption, pulmonary hypertension, and higher mortality. The primary mechanisms for this include decreased ventilatory responsiveness to hypercapnia, reduced respiratory muscle output, and marked increases in upper airway resistance. In the presence of more profound daytime hypercapnia, polysomnography should be considered (over nocturnal pulse oximetry) to rule out other co-existing sleep-related breathing disorders such as obstructive sleep apnea (overlap syndrome) and obesity hypoventilation syndrome. Present consensus guidelines provide insight into the proper use of oxygen, continuous positive airway pressure, and nocturnal noninvasive positive-pressure ventilation for those conditions, but several issues remain contentious. In order to provide optimal therapy to patients, the clinician must take into account certain reimbursement and implementation-process obstacles and the guidelines for treatment and coverage criteria.
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PMID:Chronic obstructive pulmonary disease and sleep. 1473 21


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