Emerging research highlights the complex interrelationships between sleep-disordered breathing and cardiovascular disease, presenting clinical and research opportunities as well as challenges. ...Patients presenting to cardiology clinics have a high prevalence of obstructive and central sleep apnea associated with Cheyne-Stokes respiration. Multiple mechanisms have been identified by which sleep disturbances adversely affect cardiovascular structure and function. Epidemiological research indicates that obstructive sleep apnea is associated with increases in the incidence and progression of coronary heart disease, heart failure, stroke, and atrial fibrillation. Central sleep apnea associated with Cheyne-Stokes respiration predicts incident heart failure and atrial fibrillation; among patients with heart failure, it strongly predicts mortality. Thus, a strong literature provides the mechanistic and empirical bases for considering obstructive sleep apnea and central sleep apnea associated with Cheyne-Stokes respiration as potentially modifiable risk factors for cardiovascular disease. Data from small trials provide evidence that treatment of obstructive sleep apnea with continuous positive airway pressure improves not only patient-reported outcomes such as sleepiness, quality of life, and mood but also intermediate cardiovascular end points such as blood pressure, cardiac ejection fraction, vascular parameters, and arrhythmias. However, data from large-scale randomized controlled trials do not currently support a role for positive pressure therapies for reducing cardiovascular mortality. The results of 2 recent large randomized controlled trials, published in 2015 and 2016, raise questions about the effectiveness of pressure therapies in reducing clinical end points, although 1 trial supported the beneficial effect of continuous positive airway pressure on quality of life, mood, and work absenteeism. This review provides a contextual framework for interpreting the results of recent studies, key clinical messages, and suggestions for future sleep and cardiovascular research, which include further consideration of individual risk factors, use of existing and new multimodality therapies that also address adherence, and implementation of trials that are sufficiently powered to target end points and to support subgroup analyses. These goals may best be addressed through strengthening collaboration among the cardiology, sleep medicine, and clinical trial communities.
Cardiovascular disease (CVD) remains the most prevalent cause of premature death worldwide. It had been suspected for decades that increased activity of the sympathetic nervous system (SNS) might ...play a pathogenetic role in the development and progression of hypertension, heart failure (HF) and CVD. The use of microneurographic techniques to directly assess the SNS has allowed this field to advance considerably in recent years. We now have compelling evidence for a key role of sympathetic overactivity in the pathogenesis and progression of hypertension and associated hypertension-mediated organ damage (such as endothelial dysfunction, arterial stiffness and left ventricular hypertrophy), HF (with or without reduced left ventricular ejection fraction). Sympathetic overactivity also drives increased cardiovascular risk in the settings of obesity, metabolic syndrome, chronic kidney disease and obstructive sleep apnoea, among other conditions. Thus, sympathetic overactivity is an important factor that drives patients through the CVD continuum, from the early appearance of cardiovascular risk factors, to impairments of the structure and function of components of the heart and arteries, to established CVD, and ultimately to a life-threatening cardiovascular event. A deeper understanding of the role of sympathetic overactivity in the pathogenesis of CVD and HF will support the optimization of therapeutic interventions for these conditions.
Obstructive sleep apnea (OSA) is an underdiagnosed condition characterized by recurrent episodes of obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia during ...sleep. Obesity predisposes to OSA, and the prevalence of OSA is increasing worldwide because of the ongoing epidemic of obesity. Recent evidence has shown that surrogate markers of cardiovascular risk, including sympathetic activation, systemic inflammation, and endothelial dysfunction, are significantly increased in obese patients with OSA versus those without OSA, suggesting that OSA is not simply an epiphenomenon of obesity. Moreover, findings from animal models and patients with OSA show that intermittent hypoxia exacerbates the metabolic dysfunction of obesity, augmenting insulin resistance and nonalcoholic fatty liver disease. In patients with the metabolic syndrome, the prevalence of moderate to severe OSA is very high (∼60%). In this population, OSA is independently associated with increased glucose and triglyceride levels as well as markers of inflammation, arterial stiffness, and atherosclerosis. A recent randomized, controlled, crossover study showed that effective treatment of OSA with continuous positive airway pressure for 3 months significantly reduced several components of the metabolic syndrome, including blood pressure, triglyceride levels, and visceral fat. Finally, several cohort studies have consistently shown that OSA is associated with increased cardiovascular mortality, independent of obesity. Taken together, these results support the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. Recognition and treatment of OSA may decrease the cardiovascular risk in obese patients.
Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of ...atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area.
Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is ...uncertain.
After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood.
Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood.
Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).
Obstructive sleep apnea and metabolic syndrome Giampá, Sara Q. C.; Lorenzi‐Filho, Geraldo; Drager, Luciano F.
Obesity (Silver Spring, Md.),
April 2023, 2023-04-00, 20230401, Volume:
31, Issue:
4
Journal Article
Peer reviewed
Metabolic syndrome (MS) is a heterogeneous condition associated with increased cardiovascular risk. There is growing evidence from experimental, translational, and clinical investigations that has ...suggested that obstructive sleep apnea (OSA) is associated with prevalent and incident components of MS and MS itself. The biological plausibility is supportive, primarily related to one of the main features of OSA, namely intermittent hypoxia: increased sympathetic activation with hemodynamic repercussions, increased hepatic glucose output, insulin resistance through adipose tissue inflammation, pancreatic β‐cell dysfunction, hyperlipidemia through the worsening of fasting lipid profiles, and the reduced clearance of triglyceride‐rich lipoproteins. Although there are multiple related pathways, the clinical evidence relies mainly on cross‐sectional data preventing any causality assumptions. The overlapping presence of visceral obesity or other confounders such as medications challenges the ability to understand the independent contribution of OSA on MS. In this review, we revisit the evidence on how OSA/intermittent hypoxia could mediate adverse effects of MS parameters independent of adiposity. Particular attention is devoted to discussing recent evidence from interventional studies. This review describes the research gaps, the challenges in the field, perspectives, and the need for additional high‐quality data from interventional studies addressing the impact of not only established but promising therapies for OSA/obesity.
The impact of obstructive sleep apnoea (OSA) treatment with CPAP on weight is not clear. This meta-analysis was designed to assess whether OSA treatment with CPAP promotes changes in body mass index ...(BMI) and weight.
We searched PubMed, SCOPUS and Cochrane Central Register electronic databases through 1 October 2013 (including papers in press at that time), without language restrictions. We identified randomised trials of CPAP versus controls with a minimum treatment duration of 4 weeks that objectively measured BMI. Data were independently abstracted and reviewed by two investigators using a standardised protocol.
We included a total of 3181 patients from 25 randomised trials that measured BMI and weight. All studies enrolled mainly overweight and obese patients. The fixed-effects meta-analysis revealed that CPAP promoted significant increase on BMI (Hedges' g=0.14, 95% CI 0.07 to 0.21, I(2)=16.2%) and weight (Hedges' g=0.17, 95% CI 0.10 to 0.24, I(2)=0%). The funnel plot revealed low risk of publication bias. Meta-regression analyses including age, gender, baseline BMI, baseline weight, OSA severity, CPAP compliance, use of sham CPAP, study duration, study design (crossover/parallel), study origin (Western/Eastern), recommendation for dietary changes or physical activity, revealed that no single predictor influenced the main outcome for weight. Baseline weight was a predictor of increased BMI after CPAP.
OSA treatment with CPAP promotes significant increase in BMI and weight. Additional therapies for body weight reduction must be recommended for overweight or obese patients with OSA initiated on CPAP.
Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue ...hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) inspired O₂ fraction (Fi(O₂)) 21-5%, 60/h, IH 12 times/h (Fi(O₂) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O₂) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O₂)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O₂) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O₂) was lower than in lean mice, whereas muscle and fat Pti(O₂) did not differ. During IH, Pti(O₂) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.
Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity ...and hypertension are needed.
In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m
. Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm Hg and 90 mm Hg, respectively, at 12 months.
We included 100 patients (70% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1-14.0;
<0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4-10.6;
=0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group.
Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension.
URL: https://clinicaltrials.gov. Unique identifier: NCT01784848.
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