Obstructive Sleep Apnea: An Emerging Risk Factor for Atherosclerosis
TL;DR: Clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cellactivation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction.
About: This article is published in Chest.The article was published on 2011-08-01 and is currently open access. It has received 296 citations till now. The article focuses on the topics: Cell activation & Endothelial dysfunction.
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TL;DR: Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes, and these findings may inform the discussion about the potential risks ofosterone therapy.
Abstract: percentages with events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%). In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41). CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of adverse outcomes. These findings may inform the discussion about the potential risks of testosterone therapy.
829 citations
TL;DR: The objectives of this review are to provide novel insight into each of these specific questions by integrating into contemporary understanding of relationships between sleep apnea and CVD, to introduce a hypothetical model of bidirectional causality, and to consider directions for future research.
Abstract: Sleep apnea occurs in ≈5% to 10% of the general population, regardless of race and ethnicity.1 By contrast, in patients with cardiovascular diseases (CVDs), its prevalence, depending on the specific disorder surveyed, can range between 47% and 83%.2–4 One form, central sleep apnea (CSA), is rare in the general population, but is detected often in conditions characterized by sodium and water retention, such as heart failure (HF).2 Such epidemiological observations raise several important and as yet unresolved questions: What accounts for this remarkable concentration of sleep apnea among patients with CVD and its association with fluid retaining states? Does obstructive sleep apnea (OSA) predispose at-risk individuals to develop, over time, hypertension, coronary artery disease, stroke, or HF? Conversely, could mechanisms engaged by CVD, such as activation of the sympathetic nervous and renin-angiotensin-aldosterone systems, with consequences including renal sodium retention, contribute over time to the development or exacerbation of sleep apnea? From the clinical perspective, is sleep apnea, when present in patients with CVD an epiphenomenon, perhaps related to ageing, or a causal contributor to worse prognosis? And if so, are there now sufficient data to recommend randomized controlled trials to determine whether specific treatment of sleep apnea can reduce mortality or cardiovascular event rates? Our objectives, in this review, are to provide novel insight into each of these specific questions by integrating into our contemporary understanding of relationships between sleep apnea and CVD5 newer epidemiological, observational, mechanistic, and trial data; to introduce a hypothetical model of bidirectional causality; and to consider directions for future research.
In healthy subjects, during non–rapid eye movement sleep (which constitutes ≈85% of total sleep time), efferent sympathetic nerve activity (SNA) diminishes and vagal tone increases, resulting in reductions in metabolic rate, blood pressure (BP), and heart rate (HR).6 …
319 citations
TL;DR: In conclusion, OSAS is associated with an increased risk of NAFLD, NASH and fibrosis, and OSAS patients should be screened for the presence and severity ofNAFLD.
Abstract: Summary
Obstructive sleep apnoea syndrome (OSAS) and non-alcoholic fatty liver disease (NAFLD) are common in clinical practice. NAFLD encompasses simple steatosis and non-alcoholic steatohepatitis (NASH): both confer an increased risk of cardiovascular disease and diabetes; NASH increases also liver-related risk. Growing experimental evidence connects chronic intermittent hypoxia of OSAS to NAFLD. We reviewed English and non-English articles and international meeting abstracts through December 2012. Observational studies were included if they assessed OSAS by polysomnography and NAFLD by histological, radiological or biochemical criteria. Two reviewers evaluated retrieved articles by appropriate quality scores. Main outcomes were pooled using random- or fixed-effects models. The effect of age, sex and body mass index (BMI) on effect estimates was assessed by meta-regression. Eighteen cross-sectional studies (2,183 participants) were included. Pooled odds ratios (ORs) of OSAS for the presence of NAFLD, as defined by histology, radiology, and AST or ALT elevation, were 2.01(95% CI: 1.36–2.97), 2.99(1.79–4.99), 2.36(1.46–3.82) and 2.60(1.88–3.61), respectively. Pooled ORs of OSAS for NASH, fibrosis-any stage, or advanced fibrosis in biopsy-proven NAFLD patients were 2.37(1.59–3.51), 2.16(1.45–3.20) and 2.30(1.21–4.38). The magnitude and direction of effects were unaffected by age, sex and BMI. In conclusion, OSAS is associated with an increased risk of NAFLD, NASH and fibrosis. OSAS patients should be screened for the presence and severity of NAFLD.
201 citations
TL;DR: This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients.
Abstract: This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular (in particular hypertensive) patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients. The present document is the result of work performed by a panel of experts participating in the European Union COST (Cooperation in Scientific and Technological research) Action B26 on OSA, with the endorsement of the European Respiratory Society and the European Society of Hypertension. In particular, these recommendations are aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are also aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.
198 citations
TL;DR: Leukocyte-derived microparticles, including LMPs, modify the endothelial function and promote the recruitment of inflammatory cells in the vascular wall, necessary processes for the progression of the atherosclerotic lesion.
Abstract: Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. When they carry tissue factor or coagulation inhibitors, they participate in hemostasis and pathological thrombosis. Both proinflammatory and anti-inflammatory processes can be affected by LMPs, thus ensuring an appropriate inflammatory response. LMPs also play a dual role in the endothelium by either improving the endothelial function or inducing an endothelial dysfunction. LMPs are implicated in all stages of atherosclerosis. They circulate at a high level in the bloodstream of patients with high atherothrombotic risk, such as smokers, diabetics, and subjects with obstructive sleep apnea, where their prolonged contact with the vessel wall may contribute to its overall deterioration. Numbering microparticles, including LMPs, might be useful in predicting cardiovascular events. LMPs modify the endothelial function and promote the recruitment of inflammatory cells in the vascular wall, necessary processes for the progression of the atherosclerotic lesion. In addition, LMPs favor the neovascularization within the vulnerable plaque and, in the ruptured plaque, they take part in coagulation and platelet activation. Finally, LMPs participate in angiogenesis. They might represent a novel therapeutic tool to reset the angiogenic switch in pathologies with altered angiogenesis. Additional studies are needed to further investigate the role of LMPs in cardiovascular diseases. However, large-scale studies are currently difficult to set up because microparticle measurement still requires elaborate techniques which lack standardization.
195 citations
References
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TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 citations
TL;DR: The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women, and is associated with daytime hypersomnolence.
Abstract: Background Limited data have suggested that sleep-disordered breathing, a condition of repeated episodes of apnea and hypopnea during sleep, is prevalent among adults. Data from the Wisconsin Sleep Cohort Study, a longitudinal study of the natural history of cardiopulmonary disorders of sleep, were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health. Methods A random sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep (the apnea-hypopnea score). We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score (≥ 5, ≥ 10, and ≥ 15); we used logistic regression to investigate risk factors. Results The estimated prevalence of sleep-disordered breathing, defined as an apnea-hypopnea score of 5 or higher, was 9 percent for w...
9,642 citations
TL;DR: In men, severe obstructive sleep apnoea-hypopNoea significantly increases the risk of fatal and non-fatal cardiovascular events and CPAP treatment reduces this risk.
4,132 citations
TL;DR: The histological classification of human atherosclerotic lesions found in the second part of this report led to the earlier definitions of precursor lesions, and the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes was attempted.
Abstract: This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).
3,698 citations
TL;DR: An "oxidative response to inflammation" model is proposed as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
Abstract: This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an "oxidative response to inflammation" model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.
2,518 citations