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Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

ABSTRACT: STUDY OBJECTIVES:Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in patients with OSA. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic complex that mediates protein transport in the Golgi compartment, as a potential novel biomarker of atherosclerosis. This study aimed to evaluate whether COPE-Ab levels had an association with cardiovascular and cerebrovascular events in patients with OSA. METHODS:Eighty-two adult patients with a diagnosis of OSA via polysomnography and 64 healthy donors were studied. Serum COPE-Ab levels were measured using an amplified luminescence proximity homogeneous assay. Then, clinical factors related to atherosclerosis were evaluated with respect to COPE-Ab levels. RESULTS:Significant differences in COPE-Ab levels were observed in terms of OSA severity. COPE-Ab levels were significantly higher in patients with OSA and also CVD and/or stroke, hypertension, and a high body mass index. Univariate and multivariate logistic regression analyses of patients with OSA identified elevated COPE-Ab level as a significant predictor of CVD and/or stroke. CONCLUSIONS:An elevated COPE-Ab level may be a potential predictor of the risks of cardiovascular and cerebrovascular events in patients with OSA. Therefore, patients with higher COPE-Ab levels may require more careful and intensive treatment. COMMENTARY:A commentary on this article appears in this issue on page 361.

SUBMITTER: Matsumura T

PROVIDER: S-EPMC5337586 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

Matsumura Takuma T Terada Jiro J Kinoshita Taku T Sakurai Yoriko Y Yahaba Misuzu M Ema Ryogo R Amata Atsuko A Sakao Seiichiro S Nagashima Kengo K Tatsumi Koichiro K Hiwasa Takaki T

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 20170315 3

<h4>Study objectives</h4>Although moderate to severe obstructive sleep apnea (OSA) is an independent risk factor for severe arteriosclerotic diseases such as cardiovascular disease (CVD) and stroke, the development of atherosclerosis-related diseases cannot yet be predicted in patients with OSA. In a pilot study, we identified autoantibodies against the coatomer protein complex, subunit epsilon [circulating anti-coatomer protein complex subunit epsilon autoantibody (COPE-Ab)], a cytosolic comple ...[more]

PMID: 27923433

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Project description:BackgroundObstructive sleep apnea (OSA) patients are at increased risk for pulmonary and cardiovascular complications; perioperative mortality risk is unclear. This report analyzes cases submitted to the OSA Death and Near Miss Registry, focusing on factors associated with poor outcomes after an OSA-related event. We hypothesized that more severe outcomes would be associated with OSA severity, less intense monitoring, and higher cumulative opioid doses.MethodsInclusion criteria were age ≥18 years, OSA diagnosed or suspected, event related to OSA, and event occurrence 1992 or later and <30 days postoperatively. Factors associated with death or brain damage versus other critical events were analyzed by tests of association and odds ratios (OR; 95% confidence intervals [CIs]).ResultsSixty-six cases met inclusion criteria with known OSA diagnosed in 55 (83%). Patients were middle aged (mean = 53, standard deviation [SD] = 15 years), American Society of Anesthesiologists (ASA) III (59%, n = 38), and obese (mean body mass index [BMI] = 38, SD = 9 kg/m); most had inpatient (80%, n = 51) and elective (90%, n = 56) procedures with general anesthesia (88%, n = 58). Most events occurred on the ward (56%, n = 37), and 14 (21%) occurred at home. Most events (76%, n = 50) occurred within 24 hours of anesthesia end. Ninety-seven percent (n = 64) received opioids within the 24 hours before the event, and two-thirds (41 of 62) also received sedatives. Positive airway pressure devices and/or supplemental oxygen were in use at the time of critical events in 7.5% and 52% of cases, respectively. Sixty-five percent (n = 43) of patients died or had brain damage; 35% (n = 23) experienced other critical events. Continuous central respiratory monitoring was in use for 3 of 43 (7%) of cases where death or brain damage resulted. Death or brain damage was (1) less common when the event was witnessed than unwitnessed (OR = 0.036; 95% CI, 0.007-0.181; P < .001); (2) less common with supplemental oxygen in place (OR = 0.227; 95% CI, 0.070-0.740; P = .011); (3) less common with respiratory monitoring versus no monitoring (OR = 0.109; 95% CI, 0.031-0.384; P < .001); and (4) more common in patients who received both opioids and sedatives than opioids alone (OR = 4.133; 95% CI, 1.348-12.672; P = .011). No evidence for an association was observed between outcomes and OSA severity or cumulative opioid dose.ConclusionsDeath and brain damage were more likely to occur with unwitnessed events, no supplemental oxygen, lack of respiratory monitoring, and coadministration of opioids and sedatives. It is important that efforts be directed at providing more effective monitoring for OSA patients following surgery, and clinicians consider the potentially dangerous effects of opioids and sedatives-especially when combined-when managing OSA patients postoperatively.

Project description:RationaleA total of 20-30% of respiratory events in obstructive sleep apnea are terminated without clear arousal. Arousals are thought to predispose to further events by promoting hyperventilation, hypocapnia, and upper-airway dilator muscle hypotonia. Therefore, events terminated without arousal may promote stable breathing.ObjectivesTo compare physiologic changes at respiratory event termination with American Sleep Disorders Association (ASDA) Arousal to No Arousal, and determine whether secondary respiratory events are less common and have higher dilator muscle activity after No Arousal compared with ASDA Arousal.MethodsPatients with obstructive sleep apnea wore sleep staging, genioglossus (EMG(GG)), and tensor palatini (EMG(TP)) electrodes plus a nasal mask and pneumotachograph. During stable sleep, continuous positive airway pressure (CPAP) was lowered for 3-minute periods to induce respiratory events. Physiologic variables were compared between events terminated with (1) ASDA Arousal, (2) No Arousal, or (3) sudden CPAP increase (CPAPinc, control).Measurements and main resultsSixteen subjects had adequate data. EMG(GG), EMG(TP), and heart rate increased after ASDA Arousal (340 ± 57%, 215 ± 28%, and 110.7 ± 2.3%) and No Arousal (185 ± 32%, 167 ± 15%, and 108.5 ± 1.6%) but not CPAPinc (90 ± 10%, 94 ± 11%, and 102.1 ± 1%). Ventilation increased more after ASDA Arousal than No Arousal and CPAPinc, but not after accounting for the severity of respiratory event. Fewer No Arousals were followed by secondary events than ASDA Arousals. However, low dilator muscle activity did not occur after ASDA Arousal or No Arousal (EMG(GG) rose from 75 ± 5 to 125 ± 7%) and secondary events were less severe than initial events (ventilation rose 4 ± 0.4 to 5.5 ± 0.51 L/min).ConclusionsRespiratory events that were terminated with ASDA Arousal were more severely flow-limited, had enhanced hyperventilation after event termination, and were more often followed by secondary events than No arousal. However, secondary events were not associated with low dilator muscle activity and airflow was improved after both No Arousal and ASDA Arousal.

Dataset Information

Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

Publications

Circulating Anti-Coatomer Protein Complex Subunit Epsilon (COPE) Autoantibodies as a Potential Biomarker for Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

Similar Datasets

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