Intermittent hypoxemia and OSA: implications for comorbidities.
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ABSTRACT:
SUBMITTER: Dewan NA
PROVIDER: S-EPMC4285080 | biostudies-other | 2015 Jan
REPOSITORIES: biostudies-other
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Project description:Continuous positive airway pressure (CPAP) treatment results in nearly complete remission of symptoms of obstructive sleep apnoea (OSA); however, its effect on OSA comorbidities including cardiovascular diseases remains contradictory. Here we investigated the short- and long-term effect of CPAP treatment on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with severe OSA. Serum levels of 7 MMPs and 3 TIMPs were followed in OSA patients (n = 28) with an apnoea-hypopnoea index of ≥30 events/h at the time of diagnosis and at control visits (2 months, 6 months and 5 years) after initiation of fixed-pressure CPAP treatment. The first few months of CPAP therapy resulted in significant decrease of MMP-8 and MMP-9 levels (MMP-8: 146 (79-237) vs. 287 (170-560) pg/mL; MMP-9: 10.1 (7.1-14.1) vs. 12.7 (10.4-15.6) ng/mL, p < 0.05 for each at 2 months), while the rest of the panel remained unchanged as compared to baseline values. In contrast, at 5 years, despite of uninterrupted CPAP treatment and excellent adherence the levels of MMP-8, MMP-9 and TIMPs significantly increased (p < 0.05). Our data suggest that initiation of CPAP therapy leads to a decrease in the level of key MMPs in the short-term; however, this effect is not sustained over the long-term.
| S-EPMC7248085 | biostudies-literature
Project description:PurposeObstructive sleep apnea (OSA) is independently associated with increased risk for stroke and other cardiovascular diseases. Since activated platelets play an important role in cardiovascular disease, the objective of this study was to determine whether platelet reactivity was altered in OSA subjects with intermittent nocturnal hypoxemia.MethodsThirty-one subjects, without hypertension or cardiovascular disease and not taking medication, participated in the study. Subjects were stratified based on OSA-related oxygen desaturation index (ODI) recorded during overnight polysomnography. Platelet reactivity to a broad panel of agonists (collagen, thrombin, protease-activated receptor1 hexapeptide, epinephrine, ADP) was measured by monitoring platelet aggregation and ATP secretion. Expression of platelet activation markers CD154 (CD40L) and CD62P (P-selectin) and platelet-monocyte aggregates (PMA) was quantified by flow cytometry.ResultsEpinephrine-induced platelet aggregation was substantially decreased in OSA subjects with significant intermittent hypoxemia (ODI ≥ 15) compared with subjects with milder hypoxemia levels (ODI < 15) (area under curve, p = 0.01). In addition, OSA subjects with ODI ≥ 15 exhibited decreased thrombin-induced platelet aggregation (p = 0.02) and CD40L platelet surface expression (p = 0.05). Platelet responses to the other agonists, CD62P platelet surface expression, and PMA levels were not significantly different between groups. Reduction in platelet responses to epinephrine and thrombin, and decreased CD40L surface marker expression in significant hypoxemic OSA individuals, is consistent with their platelets being in an activated state.ConclusionsIncreased platelet activation was present in otherwise healthy subjects with intermittent nocturnal hypoxemia due to underlying OSA. This prothrombotic milieu in the vasculature is likely a key contributing factor toward development of thrombosis and cardiovascular disease.Trial registrationNCT00859950.
| S-EPMC7415497 | biostudies-literature
Project description:Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may play a role in this relationship. Objectives: To determine the association between prolonged episodes of intermittent hypoxemia and severe bronchopulmonary dysplasia. Methods: A post hoc analysis of extremely preterm infants in the Canadian Oxygen Trial who survived to 36 weeks' postmenstrual age was performed. Oxygen saturations <80% for ⩾1 minute and the proportion of time per day with hypoxemia were quantified using continuous pulse oximetry data that had been sampled every 10 seconds from within 24 hours of birth until 36 weeks' postmenstrual age. The study outcome was severe bronchopulmonary dysplasia as defined in the 2001 NIH Workshop Summary. Measurements and Main Results: Of 1,018 infants, 332 (32.6%) developed severe bronchopulmonary dysplasia. The median number of hypoxemic episodes ranged from 0.8/day (interquartile range, 0.2-1.1) to 60.2/day (interquartile range, 51.4-70.3) among the least and most affected 10% of infants. Compared with the lowest decile of exposure to hypoxemic episodes, the adjusted relative risk of severe bronchopulmonary dysplasia increased progressively from 1.72 (95% confidence interval, 1.55-1.90) at the 2nd decile to 20.40 (95% confidence interval, 12.88-32.32) at the 10th decile. Similar risk gradients were observed for time in hypoxemia. Significant differences in the rates of hypoxemia between infants with and without severe bronchopulmonary dysplasia emerged within the first week after birth. Conclusions: Prolonged intermittent hypoxemia beginning in the first week after birth was associated with an increased risk of developing severe bronchopulmonary dysplasia among extremely preterm infants. Clinical trial registered with www.isrctn.com (ISRCTN62491227) and www.clinicaltrials.gov (NCT00637169).
| S-EPMC8759313 | biostudies-literature
Project description:BackgroundIntermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study aims to assess the influence and evaluate the predictive ability of IH measures on Type 1 ROP, a stage beyond which ROP treatment is indicated.MethodsIH was quantified by continuously monitoring oxygen saturation (SpO 2 ) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH variables for Type 1 ROP development.ResultsUnivariate analyses suggested that IH measures are greater in infants with Type 1 ROP and are predictive of Type 1 ROP development. Multivariable logistic regression analyses revealed that cumulative IH of longer duration during certain postnatal periods are associated with Type 1 ROP development after adjusting for gestational age (GA) or birth weight (BW). Although area under the curve (AUC) analyses revealed added predictivity of cumulative IH variables above GA or BW, these increments in AUC were not statistically significant.ConclusionsThe duration of IH events was associated with Type 1 ROP development. Interventions for reducing the duration of IH events may potentially improve ROP outcomes.ImpactThis study investigates the impact of IH on the development of Type 1 ROP in preterm infants.Univariate analyses revealed that IH measures are greater in infants with Type 1 ROP and are predictive of Type 1 ROP development.Multivariable logistic regression analyses revealed that cumulative IH events of longer duration are associated with Type 1 ROP development after adjusting for GA or BW.Interventions for reducing the duration of IH events during critical postnatal periods may potentially improve ROP outcomes.
| S-EPMC10557831 | biostudies-literature
Project description:ObjectivesDetection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks' gestational age (GA)) on versus off invasive mechanical ventilation.Study designRetrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and ≥5d antibiotics).ResultsFor infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783.ConclusionWe identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.
| S-EPMC10854335 | biostudies-literature
Project description:Background and Objectives: Obstructive sleep apnea (OSA) is associated with daytime somnolence, cognitive impairment and high cardiovascular morbidity and mortality. Obesity, associated cardiovascular comorbidities, accelerated erythropoiesis and muscular mitochondrial energetic dysfunctions negatively influence exercise tolerance in moderate-severe OSA patients. The cardiopulmonary exercise testing (CPET) offers an integrated assessment of the individual's aerobic capacity and helps distinguish the main causes of exercise limitation. The purpose of this study is to evaluate the aerobic capacity of OSA patients, before and after short-term continuous positive airway pressure (CPAP). Materials and Methods: Our prospective study included 64 patients with newly diagnosed moderate-severe OSA (apnea hypopnea index (AHI) 39.96 ± 19.04 events/h) who underwent CPET before and after CPAP. Thirteen patients were unable to tolerate CPAP or were lost during follow-up. Results: 49.29% of our patients exhibited a moderate or severe decrease in functional capacity (Weber C or D). CPET performance was influenced by gender but not by apnea severity. Eight weeks of CPAP induced significant improvements in maximal exercise load (? = 14.23 W, p = 0.0004), maximum oxygen uptake (? = 203.87 mL/min, p = 0.004), anaerobic threshold (? = 316.4 mL/min, p = 0.001), minute ventilation (? = 5.1 L/min, p = 0.01) and peak oxygen pulse (? = 2.46, p = 0.007) as well as a decrease in basal metabolic rate (BMR) (? = -8.3 kCal/24 h, p = 0.04) and average Epworth score (? = -4.58 points, p < 0.000001). Conclusions: Patients with moderate-severe OSA have mediocre functional capacity. Apnea severity (AHI) was correlated with basal metabolic rate, resting heart rate and percent predicted maximum effort but not with anaerobic threshold or maximum oxygen uptake. Although CPET performance was similar in the two apnea severity subgroups, short-term CPAP therapy significantly improved most CPET parameters, suggesting that OSA per se has a negative influence on effort capacity.
| S-EPMC7074283 | biostudies-literature
Project description:STUDY OBJECTIVES:Apnea-hypopnea index (AHI) is the main polysomnographic measure to diagnose obstructive sleep apnea (OSA). We aimed to evaluate the effect of three standard hypopnea definitions on the prevalence of OSA and its association with cardiometabolic outcomes in the general population. METHODS:We analyzed data from the HypnoLaus study (Lausanne, Switzerland), in which 2,162 participants (51% women, 57 ± 19 years) underwent in-home full polysomnography. AHI was calculated using three hypopnea definitions: AASM1999 (≥ 50% decrease in airflow or lower airflow reduction associated with oxygen desaturation ≥ 3% or an arousal), AASM2007 (≥ 30% airflow reduction associated with ≥ 4% oxygen desaturation), and AASM2012 (≥ 30% airflow reduction associated with ≥ 3% oxygen desaturation or an arousal). Participants underwent clinical assessment for hypertension, diabetes, and metabolic syndrome. RESULTS:Median AHI of AASM1999, AASM2007 and AASM2012 criteria were 10.9, 4.4, and 10.1 events/h, respectively. OSA prevalence defined as AHI ≥ 5, ≥ 15, and ≥ 30 events/h was 74.5%, 39.3%, and 16.3% using AASM1999; 46.9%, 18.8%, and 6.8% using AASM2007; and 72.2%, 36.6%, and 14.9% using AASM2012. Different AHI thresholds derived from AASM1999, AASM2007, and AASM2012 criteria, respectively, were associated with hypertension (11.5, 4.8, 10.7 events/h), diabetes (15.7, 7.1, 14.4 events/h), and metabolic syndrome (12.8, 5.5, 11.8 events/h). CONCLUSIONS:Hypopnea definition has a major effect on AHI and on OSA prevalence in the general population and, hence, important implications for public health policies. There is a twofold difference in the threshold above which an association with diabetes, hypertension, and metabolic syndrome is observed using AASM2007 compared to AASM1999 or AASM2012 criteria.
| S-EPMC6374086 | biostudies-literature
Project description:Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients' exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea-hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.
| S-EPMC8874769 | biostudies-literature
Project description:Introduction: Hypoxemia is a critical component of several respiratory diseases and is known to be involved in the processes underlying co-morbidities associated to such disorders, notably at the cardiovascular level. Circulating level of Adiponectin (Ad), known as a metabolic regulator and cardio-protective hormone was previously suggested to be reduced by hypoxia but consequences of such variation are unclear. The evaluation of the specific effect of hypoxemia on Ad forms and receptors could improve the understanding of the involvement of Ad axis in hypoxemia-related diseases. Methods: Ad-pathway components were investigated in a murine model of sustained intermittent hypoxemia (FiO2 10%, 8 h/day, 35 days). Results: Sustained intermittent hypoxemia (SIH) induced a redistribution of Ad multimers in favor of HMW forms, without change in total plasmatic level. Mice submitted to hypoxia also exhibited tissue-specific modification of adiporeceptor (AdipoR) protein level without mRNA expression change. A decreased AdipoR2 abundance was observed in skeletal muscle and heart whereas AdipoR1 level was only reduced in muscle. No change was observed in liver regarding AdipoR. Lipid profile was unchanged but glucose tolerance increased in hypoxemic mice. Conclusion: Sustained intermittent hypoxemia, per se, modify Ad oligomerization state as well as AdipoR protein abundance in a tissue-specific way. That suggests alteration in Ad-dependant pathways in pathological conditions associated to SIH. Investigation of Ad-pathway components could therefore constitute useful complementary criteria for the clustering of patients with hypoxemia-related diseases and management of co-morbidities, as well as to develop new therapeutic strategies.
| S-EPMC6376175 | biostudies-literature
Project description:Coronavirus-19 (COVID-19), the infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has wreaked havoc across the globe since its emergence in December 2019. Reports of patients presenting with syncope and pre-syncope, as well as hypoxemia without symptoms of dyspnea ("silent hypoxemia"), have led researchers to speculate whether SARS-CoV-2 can alter autonomic nervous system function. As viral infections are commonly reported triggers of altered autonomic control, we must consider whether SARS-CoV-2 can also interfere with autonomic activity, at least in some patients. As we are still in the early stages of understanding COVID-19, we still do not know whether syncope and silent hypoxemia are more strongly associated with COVID-19 compared to any other viral infections that severely compromise gas exchange. Therefore, in this perspective we discuss these two intriguing clinical presentations, as they relate to autonomic nervous system function. In our discussion, we will explore COVID-specific, as well as non-COVID specific mechanisms that may affect autonomic activity and potential therapeutic targets. As we move forward in our understanding of COVID-19, well-designed prospective studies with appropriate control and comparator groups will be necessary to identify potential unique effects of COVID-19 on autonomic function.
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