Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly ...among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear.
Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5 nM insulin-induced pAKT/AKT expression changes by western blotting.
When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n = 24; p < 0.001), while no such changes occur in untreated patients (n = 8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naive murine adipocytes, without altering pre-adipocyte differentiation.
Using in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.
Background: Obesity is a coronary risk factor associated to myocardial infarction although waist to-hip-ratio has shown higher predictive power.
Objective: The aim of this study was a Receiver ...Operating Characteristic anthropometric analysis in infarcted males to identify the strength of association for simple measurements, obesity and indicators such as, waist to-hip-ratios, waist to-height-ratios and conicity index.
Methods:Case-control study of myocardial infarction in European males. One hundred and twelve cases and 112 controls aged 30-74 years were enrolled. We measured weight, height, waist circumference, umbilical waist circumference and hip circumference. We calculated various anthropometric indicators. We obtained the areas under the ROC curves, the odds ratio and correlations for measurements and anthropometric indicators.
Results: Body mass index AUC: 0.686, 95% CI (0.616-0.755); OR: 3.3, waist circumference AUC: 0.734, 95% CI (0.668-0.800); OR: 5.7, height AUC: 0.623, 95% CI (0.550-0.696); OR: 2.3, hip circumference AUC: 0.555, 95% CI (0.479-0.631); OR: 1, waist to-hip-ratio AUC: 0.796, 95% CI (0.737-0.855); OR: 9.9, umbilical waist to-hip-ratio AUC: 0.830, 95% CI (0.729-0.847); OR: 5.5, umbilical waist to-height-ratio AUC: 0.788, 95% CI (0.729-0.847); OR: 7.5, conicity index AUC: 0.795; 95% CI (0.738-0.853); OR: 9. The correlations for waist to-height-ratios and conicity index were strong (all r ≥ 0.85; p < 0.001).
Conclusions: Waist and height are measurements of associated independent risk. Hip circumference does no show discriminatory power. Obesity and waist-ratios are associated to myocardial infarction with different strength. Between other indicators, general obesity is more weakly associated. Waist to-hip-ratios present the best ROC curves but it occur information bias of their predictive power of risk. Umbilical waist to-height-ratio and conicity index present high discriminatory power and the best anthropometric risk correlations that support its use for the identification of obesity as risk factor associated to myocardial infarction and in all strategies for coronary health promotion.
Obesity hypoventilation syndrome (OHS) is a sleep disorder that has acquired great importance worldwide because of its prevalence and association with obesity leading to increased morbidity and ...mortality with reduced quality of life. The primary feature is insufficient sleep-related ventilation, resulting in abnormally elevated arterial carbon dioxide pressure (PaCO
2
) during sleep and demonstration of daytime hypoventilation. There are three main mechanisms that can generate diurnal hypoventilation in obese patients: alteration of the respiratory mechanics secondary to obesity; central hypoventilation secondary to leptin resistance and sleep disorder with sleep hypoventilation and obstructive apnoeas, which can be potentially solved with the use of positive airway pressure: non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP). There are no established guidelines for the treatment of OHS, and only a few randomised controlled trials have been published. In this review, we have gone over the role of positive airway pressure, in particular the mechanisms that produce improvement, ventilatory modes available, clinical applications, technical considerations and future research. In addition, we added a review on NIV efficacy in chronic obstructive pulmonary disease (COPD), both in acute respiratory failure due to exacerbation and mainly in stable setting where more controversy and scientific contributions are coming.
Abstract Background: the waist-to-hip ratio (WHR) is widely used to evaluate the association of abdominal obesity with myocardial infarction (MI). Objective: our aim was to determine whether ...WHR-associated risk provides a bias. Methods: a case-control study in 252 men. Stratification was used as an approach for removing bias effects. We created a baseline covariate (WHR0.95-0.99) from a new matched sample in the stratum between 0.95 and 0.99. This stratum coincides with the overlap area of the distribution, where all subjects have a similar propensity score. We considered other covariate (WHRS), conditioned on WHR < 1 and waist circumference (WC) being assigned a spurious risk. We hypothesized that subtracting hip circumference from WC (WHD) can be essential to observe the confounding effect provided by WHR. Results: BMI: AUC: 0.694, 95 % CI (0.628-0.760); OR: 3.8. WC: AUC: 0.743, 95 % CI (0.681-0.805); OR: 5.7. WHR: AUC: 0.798, 95 % CI (0.740-0.855); OR: 8.6. Waist-height ratio (WHtR): AUC: 0.782, 95 % CI (0.724-0.840); OR: 8.5. WHD: AUC: 0.204, 95 % CI (0.146-0.261); OR: 0.36. Prevalence in cases: WHR ≥ 0.95 (84.1 % vs. 38 %; OR: 8.6); WHR < 1 (36.3 % vs. 85.7 %; OR: 2.3); WHR ≥ 1 (63.4 % vs. 14.2 %; OR: 4.4); WC ≥ 94.4 (71.4 % vs. 30.1 %; OR: 5.7); WHD ≥ 2.2 (27.7 % vs. 75.3 %; OR: 7.9); WHRs (50 % vs. 25 %; OR: 2). Conclusions: WHR provides an association bias in MI cases. This can be extrapolated to other study populations. The bias is explained by a mathematical misconception where the protective effect of HC is overestimated concerning WC and height. The risk associated with WHR as higher than that associated with WC and WHtR entails anthropometric inconsistency and bias, to the extent of becoming epidemiologically false.
General practitioners play a passive role in obstructive sleep apnea (OSA) management. Simplification of the diagnosis and use of a semiautomatic algorithm for treatment can facilitate the ...integration of general practitioners, which has cost advantages.
To determine differences in effectiveness between primary health care area (PHA) and in-laboratory specialized management protocols during 6 months of follow-up.
A multicenter, noninferiority, randomized, controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in six tertiary hospitals in Spain. Sequentially screened patients with an intermediate to high OSA probability were randomized to PHA or in-laboratory management. The PHA arm involved a portable monitor with automatic scoring and semiautomatic therapeutic decision-making. The in-laboratory arm included polysomnography and specialized therapeutic decision-making. Patients in both arms received continuous positive airway pressure treatment or sleep hygiene and dietary treatment alone. The primary outcome measure was the Epworth Sleepiness Scale. Secondary outcomes were health-related quality of life, blood pressure, incidence of cardiovascular events, hospital resource utilization, continuous positive airway pressure adherence, and within-trial costs.
In total, 307 patients were randomized and 303 were included in the intention-to-treat analysis. Based on the Epworth Sleepiness Scale, the PHA protocol was noninferior to the in-laboratory protocol. Secondary outcome variables were similar between the protocols. The cost-effectiveness relationship favored the PHA arm, with a cost difference of €537.8 per patient.
PHA management may be an alternative to in-laboratory management for patients with an intermediate to high OSA probability. Given the clear economic advantage of outpatient management, this finding could change established clinical practice.Clinical trial registered with www.clinicaltrials.gov (NCT02141165).
Pulmonary hypertension (PH) is prevalent in obesity hypoventilation syndrome (OHS). However, there is a paucity of data assessing pathogenic factors associated with PH. Our objective is to assess ...risk factors that may be involved in the pathogenesis of PH in untreated OHS.
In a post hoc analysis of the Pickwick trial, we performed a bivariate analysis of baseline characteristics between patients with and without PH. Variables with a
value ≤ .10 were defined as potential risk factors and were grouped by theoretical pathogenic mechanisms in several adjusted models. Similar analysis was carried out for the 2 OHS phenotypes, with and without severe concomitant obstructive sleep apnea.
Of 246 patients with OHS, 122 (50%) had echocardiographic evidence of PH defined as systolic pulmonary artery pressure ≥ 40 mm Hg. Lower levels of awake PaO
and higher body mass index were independent risk factors in the multivariate model, with a negative and positive adjusted linear association, respectively (adjusted odds ratio 0.96; 95% confidence interval 0.93 to 0.98;
= .003 for PaO
, and 1.07; 95% confidence interval 1.03 to 1.12;
= .001 for body mass index). In separate analyses, body mass index and PaO
were independent risk factors in the severe obstructive sleep apnea phenotype, whereas body mass index and peak in-flow velocity in early/late diastole ratio were independent risk factors in the nonsevere obstructive sleep apnea phenotype.
This study identifies obesity per se as a major independent risk factor for PH, regardless of OHS phenotype. Therapeutic interventions targeting weight loss may play a critical role in improving PH in this patient population.
Registry: Clinicaltrial.gov; Name: Alternative of Treatment in Obesity Hypoventilation Syndrome; URL: https://clinicaltrials.gov/ct2/show/NCT01405976; Identifier: NCT01405976.
Masa JF, Benítez ID, Javaheri S, et al. Risk factors associated with pulmonary hypertension in obesity hypoventilation syndrome.
. 2022;18(4):983-992.
Noninvasive ventilation (NIV) is an effective form of treatment in obesity hypoventilation syndrome (OHS) with severe OSA. However, there is paucity of evidence in patients with OHS without severe ...OSA phenotype.
Is NIV effective in OHS without severe OSA phenotype?
In this multicenter, open-label parallel group clinical trial performed at 16 sites in Spain, we randomly assigned 98 stable ambulatory patients with untreated OHS and apnea-hypopnea index < 30 events/h (ie, no severe OSA) to NIV or lifestyle modification (control group) using simple randomization through an electronic database. The primary end point was hospitalization days per year. Secondary end points included other hospital resource utilization, incident cardiovascular events, mortality, respiratory functional tests, BP, quality of life, sleepiness, and other clinical symptoms. Both investigators and patients were aware of the treatment allocation; however, treating physicians from the routine care team were not aware of patients’ enrollment in the clinical trial. The study was stopped early in its eighth year because of difficulty identifying patients with OHS without severe OSA. The analysis was performed according to intention-to-treat and per-protocol principles and by adherence subgroups.
Forty-nine patients in the NIV group and 49 in the control group were randomized, and 48 patients in each group were analyzed. During a median follow-up of 4.98 years (interquartile range, 2.98-6.62), the mean hospitalization days per year ± SD was 2.60 ± 5.31 in the control group and 2.71 ± 4.52 in the NIV group (adjusted rate ratio, 1.07; 95% CI, 0.44-2.59; P = .882). NIV therapy, in contrast with the control group, produced significant longitudinal improvement in Paco2, pH, bicarbonate, quality of life (Medical Outcome Survey Short Form 36 physical component), and daytime sleepiness. Moreover, per-protocol analysis showed a statistically significant difference for the time until the first ED visit favoring NIV. In the subgroup with high NIV adherence, the time until the first event of hospital admission, ED visit, and mortality was longer than in the low adherence subgroup. Adverse events were similar between arms.
In stable ambulatory patients with OHS without severe OSA, NIV and lifestyle modification had similar long-term hospitalization days per year. A more intensive program aimed at improving NIV adherence may lead to better outcomes. Larger studies are necessary to better determine the long-term benefit of NIV in this subgroup of OHS.
ClinicalTrials.gov; No.: NCT01405976; URL: www.clinicaltrials.gov ;
Home respiratory polygraphy may be a simpler alternative to in-laboratory polysomnography for the management of more symptomatic patients with obstructive sleep apnea, but its effectiveness has not ...been evaluated across a broad clinical spectrum.
To compare the long-term effectiveness (6 mo) of home respiratory polygraphy and polysomnography management protocols in patients with intermediate-to-high sleep apnea suspicion (most patients requiring a sleep study).
A multicentric, noninferiority, randomized controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in 12 tertiary hospitals in Spain. Sequentially screened patients with sleep apnea suspicion were randomized to respiratory polygraphy or polysomnography protocols. Moreover, both arms received standardized therapeutic decision-making, continuous positive airway pressure (CPAP) treatment or a healthy habit assessment, auto-CPAP titration (for CPAP indication), health-related quality-of-life questionnaires, 24-hour blood pressure monitoring, and polysomnography at the end of follow-up. The main outcome was the Epworth Sleepiness Scale measurement. The noninferiority criterion was -2 points on the Epworth scale.
In total, 430 patients were randomized. The respiratory polygraphy protocol was noninferior to the polysomnography protocol based on the Epworth scale. Quality of life, blood pressure, and polysomnography were similar between protocols. Respiratory polygraphy was the most cost-effective protocol, with a lower per-patient cost of 416.7€.
Home respiratory polygraphy management is similarly effective to polysomnography, with a substantially lower cost. Therefore, polysomnography is not necessary for most patients with suspected sleep apnea. This finding could change established clinical practice, with a clear economic benefit. Clinical trial registered with www.clinicaltrials.gov (NCT 01752556).
Objective: The aim of this study was to realize an anthropometric analysis including common indicators, somatotype rating and body fatness (BF) in males with myocardial infarction (MI) Methods: ...Cross-sectional study of 116 males aged 30-75 years. Results: Weight (81.6±13.2 kg); height (169.4±7.1 cm); waist circumference (WC) (98.3±18.5 cm); umbilical circumference (102.4 ±21.8); hip circumference (99.3±13.6 cm); body mass index (BMI) (28.4±4 kg/m2); waist-hip ratio (WHR) (0.99±0.1, CI: 0.97-1)); waist-height ratio (WHtR) (0.58±0.1, CI: 0.56-0.60); BF (27.4%±4.5); endomorphy (4.6±1.3); mesomorphy (5.7±1.2); ectomorphy (0.8±0.8); conicity index (1.30±0.17). Correlations: BMI: BF (0.70), WC (0.70), WHR (0.48), WHtR (0.72), endomorphy (0.82), mesomorphy (0.81), ectomorphy (-0.81); WHR: BF (0.38), WC (0.69), endomorphy (0.39), mesomorphy (0.38); WHtR: BF (0.50), WC (0.96), endomorphy (0.58), mesomorphy (0.56), ectomorphy (-0.56); conicity index: WC (0.85), WHR (0.58), WHtR (0.85), endomorphy (0.45). Prevalence: WHtR (92%), WHR ≥0.95 (87%), conicity index (86.7%), WHR ≥1 (64%), BF ≥25 (69.4%), BMI ≥25-29.9 (45.6%), BMI ≥30 (37%), endomorphy ≥4.5 (47.2%), mesomorphy ≥5.6 (50%), ectomorphy ≤1.1 (71%). Conclusions: MI males present a high-risk anthropometric profile. The somatotype rating is endomorphic-mesomorph. Waist, hip and height measurements show different involvement on the body composition. BMI-defined obesity appears to be the indicator with the more weak association and it does not discriminate between body components. WHR presents high prevalence but a weak relationship with the body composition of risk. WHtR reflects body volume distribution and the best correlations with the risk bodily components, actually being the most prevalent and accurate index to explain the biological risk associated to MI.
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