scholarly journals High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea

2021 ◽  
Vol 10 (7) ◽  
pp. 1387
Author(s):  
Raphael Boneberg ◽  
Anita Pardun ◽  
Lena Hannemann ◽  
Olaf Hildebrandt ◽  
Ulrich Koehler ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Vascular Risk Factor ◽  
High Plasma ◽  
Apnea Hypopnea Index ◽  
Hypoxic Stress ◽  
Peripheral Blood Mononuclear ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

scholarly journals Identification of key genes and immune infiltration modulated by CPAP in obstructive sleep apnea by integrated bioinformatics analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255708
Author(s):  
Cheng Fan ◽  
Shiyuan Huang ◽  
Chunhua Xiang ◽  
Tianhui An ◽  
Yi Song
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Upper Airway ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Peripheral Blood Mononuclear ◽  
Immune Infiltration ◽  
Obstructive Sleep ◽  
Key Genes

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling, and continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remain elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 was downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.

scholarly journals H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Chien-Hung Chin ◽  
Chang-Chun Hsiao ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Reactive Protein ◽  
Primary Snoring ◽  
Obstructive Sleep

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

scholarly journals Prospective Screening for Primary Aldosteronism in Patients With Suspected Obstructive Sleep Apnea

Hypertension ◽  
2021 ◽  
Author(s):  
Min Ru Chee ◽  
Jesse Hoo ◽  
Renata Libianto ◽  
Stella M. Gwini ◽  
Garun Hamilton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Primary Aldosteronism ◽  
Blood Pressure Monitoring ◽  
Apnea Hypopnea Index ◽  
Hypertension Status ◽  
Antihypertensive Medications ◽  
Sleep Study ◽  
Obstructive Sleep

Several studies have demonstrated a bidirectional relationship between obstructive sleep apnea and primary aldosteronism (PA); however, many of these studies are limited to patients with known obstructive sleep apnea, hypertension, or PA. We evaluated the role of screening for PA in all patients referred for a diagnostic sleep study without selecting for prior diagnoses with these conditions. Plasma aldosterone and renin concentration were measured after an overnight polysomnography. Blood pressure was measured at the sleep center for all patients, while a proportion underwent 24-hour blood pressure monitoring. Of the 85 participating patients, 2 (2.4%) were identified to have likely PA based on an elevated aldosterone:renin ratio and/or clinical characteristics. Another 10 (11.8%) were identified to have possible PA based on their low or normal plasma renin concentration despite taking antihypertensive medications that are known to elevate renin. In participants with both obstructive sleep apnea and hypertension (n=40), the prevalence of likely or possible PA was 30%. However, there was no correlation between aldosterone, rennin, or aldosterone:renin ratio and the apnea-hypopnea index using multiple regression analysis adjusted for interfering medications and hypertension status. The observed high prevalence of possible PA among those with both hypertension and obstructive sleep apnea suggests that they should be routinely screened for PA.

scholarly journals Blood pressure profiles in patients with arterial hypertension and obstructive sleep apnea in different age groups

2021 ◽  
Vol 27 (5) ◽  
pp. 530-535
Author(s):  
A. N. Kuchmin ◽  
V. V. Ekimov ◽  
D. A. Galaktionov ◽  
I. M. Borisov ◽  
A. A. Sheveliov ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Age Groups ◽  
Pressure Profile ◽  
Control Group ◽  
Apnea Hypopnea Index ◽  
Blood Pressure Profile ◽  
Pressure Profiles ◽  
Obstructive Sleep

Background. Obstructive sleep apnea (OSA) is frequently associated with hypertension (HTN), and about 50 % hypertensive patients have concomitant OSA. Episodes of transient upper airway obstruction affect the daily blood pressure profile, leading to nocturnal HTN. Although the general relationship between OSA and the daily blood pressure profile is known, the association between the frequency of various daily blood pressure profiles and OSA severity as well as the age-specific differences remain unknown. The aim of the study was to determine the daily blood pressure profiles in patients with HTN and OSA, depending on the OSA severity and age. Design and methods. The study included 236 HTN patients underwent treatment in the period from 2008 to 2021 years and were diagnosed with OSA by cardiorespiratory monitoring: 84 patients had mild OSA (apnea/hypopnea index (AHI) < 15 episodes/h), 46 patients — moderate OSA (15 ≤ AHI < 30 episodes/h), and 106 patients — severe OSA (AHI ≥ 30 episodes/h). The control group included 140 HTN patients without OSA. Both groups were divided into 3 age subgroups: younger than 45 years, 45–59 years and ≥ 60 years. At baseline, all patients underwent cardiorespiratory monitoring (“Kardiotekhnika‑07–3/12P”, Inkart, St Petersburg, Russia) and 24-hour blood pressure (BP) monitoring (BPLab, Nizhny Novgorod, Russia). Results. We found an association between the distribution of daily BP profiles and age, which differs from that in HTN patients without OSA. Non-dipper and night-peaker BP profiles are predominant in young and middle age. Among OSA patients, the severity of OSA was associated with the BP profiles only in the young and middleage groups. Unfavorable BP profiles (non-dipper and night-peaker) were more common in patients with severe OSA, which was not observed in elderly subgroup. In the elderly, compared to younger patients, the overdipper profile was the most common and its frequency was not associated with OSA severity. Conclusions. The study shows the relationship between the age of patients with HTN and OSA, the OSA severity and the distribution of daily BP profiles.

Abstract 2462: Obstructive Sleep Apnea Treatment Improves the Blood Pressure Behavior in Normotensive Patients: A Randomized Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Luciano F Drager ◽  
Patrícia M Diniz ◽  
Luzia Diegues-Silva ◽  
Roberta B Couto ◽  
Rodrigo P Pedrosa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Randomized Study ◽  
Control Group ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
The Impact ◽  
Current Guidelines ◽  
Concomitant Hypertension

Introduction: Obstructive sleep apnea (OSA) promotes significant alterations on blood pressure during sleep. In patients with concomitant hypertension, the treatment with continuous positive airway pressure (CPAP) promotes significant reductions on blood pressure. However, the impact of CPAP on 24 hour blood pressure in normotensive patients is poorly understood. Methods: We included 22 apparently healthy patients with severe OSA defined by polysomnography (apnea/hypopnea index (AHI) >30 events/hour). We excluded hypertension according current guidelines by office measurements. They were randomized to no treatment (control) or CPAP for 3 months. At baseline and at the end of the protocol, we performed 24 hour blood pressure (BP) monitoring evaluating daytime and nighttime BP as well as the morning surge (average of systolic BP during the 2 hours after awakening minus the average of systolic BP during the 1 hour that included the lowest nighttime BP) and highest systolic nighttime BP (mean of 3 BP measurements, centered on the highest nighttime reading). Results: After 3 months, patients randomized to CPAP (mean CPAP usage: 6 hours) presented a significant reduction on daytime (80.3±6.3 to 75.3±6.9 mmHg; P=0.02) and nighttime diastolic BP (67.8±9.5 to 61.4±7.5 mmHg; P=0.03). In addition, we observed a significant reduction on highest nighttime systolic BP (120.0±13.6 to 112.0±.9 mmHg; P=0.02) with a trend for a reduction on morning surge (22.3±9.2 to 17.3±.4 mmHg; P=0.08). No significant alterations occurred in the control group. Conclusion: Even in the absence of established hypertension, CPAP therapy improved the behavior of 24 hour BP in patients with severe OSA.

Effect of Adenotonsillectomy on Ambulatory Blood Pressure in Pediatric Obstructive Sleep Apnea: 6-Month Follow-up Study

2019 ◽  
Vol 160 (5) ◽  
pp. 911-921 ◽  
Author(s):  
Kun-Tai Kang ◽  
Shuenn-Nan Chiu ◽  
Che-Yi Lin ◽  
Wen-Chin Weng ◽  
Pei-Lin Lee ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Ambulatory Blood Pressure ◽  
Apnea Hypopnea Index ◽  
Study Cohort ◽  
Obstructive Sleep ◽  
Pressure Changes

Objective To investigate 24-hour ambulatory blood pressure changes 6 months after surgery among children with obstructive sleep apnea. Study Design Prospective interventional study. Setting Tertiary medical hospital. Subjects and Methods Children aged 4 to 16 years with symptoms of obstructive sleep apnea (apnea-hypopnea index >1) were recruited. All children underwent adenotonsillectomy and postoperative polysomnography overnight. The 24-hour ambulatory blood pressure was measured before and 6 months after surgery. Results The study cohort enrolled 124 children: mean (SD) age, 7.3 (3.1) years; 73% boys. After surgery, the apnea-hypopnea index significantly decreased from 13.3 (18.1) to 3.3 (7.2) events per hour ( P < .001). Overall systolic blood pressure and diastolic blood pressure were not significantly different following surgery, while daytime systolic blood pressure was slightly increased (114.3 to 117.3 mm Hg, P < .01) postoperatively. The hypertensive group (n = 43) exhibited significantly decreased levels of overall diastolic, nighttime systolic, and nighttime diastolic blood pressure ( P < .05), and 54% of hypertensive children became nonhypertensive after surgery. The nonhypertensive group (n = 81) showed slightly increased levels of nocturnal overall systolic, daytime systolic, and nighttime systolic blood pressure. A generalized linear mixed model revealed that children with hypertension had a greater decrease in systolic and diastolic ambulatory blood pressure during the daytime and nighttime (all P < .05) than those without hypertension. Conclusions Ambulatory blood pressure changes after adenotonsillectomy among children with obstructive sleep apnea are minimal. The decrease in ambulatory blood pressure after surgery is more prominent for hypertensive children than nonhypertensive children.

Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study

2016 ◽  
Vol 41 (5-6) ◽  
pp. 233-241 ◽  
Author(s):  
Brian B. Koo ◽  
Daawn M. Bravata ◽  
Lauren A. Tobias ◽  
Jason S. Mackey ◽  
Edward J. Miech ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Ambulatory Blood Pressure ◽  
Blood Pressure Monitoring ◽  
Oxygen Desaturation ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
Nighttime Blood Pressure ◽  
The Mean

Background: Wake-up stroke (WUS) accounts for a quarter of all ischemic strokes. Its conspicuous occurrence during sleep suggests that WUS may be associated with obstructive sleep apnea (OSA). We investigated the potential association among WUS, OSA, and measures of sympathetic hyperactivity. Methods: This is a cross-sectional analysis of data from the Sleep Apnea in Transient Ischemic Attack and Stroke (SLEEP TIGHT) study. Ischemic stroke patients were divided into WUS and non-WUS groups. Participants underwent polysomnography and ambulatory blood pressure monitoring. Collected data included demographic, medical, stroke characteristics (including severity by National Institutes of Health Stroke Scale), cholesterol, serum catecholamines, C-reactive protein, interleukin-6, B-type natriuretic peptide, blood pressure, and polysomnographic (apnea-hypopnea index (AHI); measures of hypoxia). Because both stroke and OSA affect men and women to varying degrees, the cohort was considered as a whole and by gender stratification. Results: Among 164 participants, 30.3% had WUS. The mean age was 62.0 ± 11.3 and the mean body mass index was 30.2 ± 7.9 kg/m2. One-hundred-and-five participants (63.6%) were males and 92 participants (56.8%) were Caucasian. Neither AHI nor OSA (AHI ≥5) frequency differed between WUS and non-WUS groups. Men tended to be more likely than women to have WUS (74.0 vs. 59.6%; p = 0.08), but this was not statistically significant. In gender-stratified analyses, men with WUS compared to men with non-WUS had significantly higher rates of severe OSA (AHI >30: 45.0 vs. 17.6%; p = 0.03) and tended toward more 3% oxygen desaturation events (57.0 ± 63.9 vs. 31.8 ± 22.9; p = 0.06). These differences were not seen in women. WUS patients tended to be of the male gender (74.0 vs. 59.6%; p = 0.08). History of stroke, hypertension, diabetes, dyslipidemia, or atrial fibrillation, serum catecholamines, and inflammatory biomarkers was no different between the groups. Low-density lipoprotein (LDL) was significantly higher in WUS (114.5 ± 36.3 vs. 101.4 ± 37.6; p = 0.04). Baseline diastolic blood pressure (DBP) was significantly greater in the WUS group. There was no difference in systolic or ambulatory blood pressure (including nighttime blood pressure) between WUS and non-WUS groups. Conclusions: WUS may be associated with severe OSA with more oxygen desaturation in men but not in women. WUS may be associated with high DBP and increased LDL cholesterol.

scholarly journals Identification of key genes and immune infiltration modulated by CPAP in Obstructive sleep apnea by integrated bioinformatics analysis

2021 ◽  
Author(s):  
yi Song ◽  
Cheng Fan ◽  
Shiyuan Huang ◽  
Chunhua Xiang ◽  
Tianhui An
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Upper Airway ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Peripheral Blood Mononuclear ◽  
Immune Infiltration ◽  
Obstructive Sleep ◽  
Key Genes

Patients with obstructive sleep apnea (OSA) experience partial or complete upper airway collapses during sleep resulting in nocturnal hypoxia-normoxia cycling. And continuous positive airway pressure (CPAP) is the golden treatment for OSA. Nevertheless, the exact mechanisms of action, especially the transcriptome effect of CPAP on OSA patients, remains elusive. The goal of this study was to evaluate the longitudinal alterations in peripheral blood mononuclear cells transcriptome profiles of OSA patients in order to identify the hub gene and immune response. GSE133601 were downloaded from Gene Expression Omnibus (GEO). We identified black module via weighted gene co-expression network analysis (WGCNA), the genes in which were correlated significantly with the clinical trait of CPAP treatment. Finally, eleven hub genes (TRAV10, SNORA36A, RPL10, OBP2B, IGLV1-40, H2BC8, ESAM, DNASE1L3, CD22, ANK3, ACP3) were traced and used to construct a random forest model to predict therapeutic efficacy of CPAP in OSA with a good performance with AUC of 0.92. We further studied the immune cells infiltration in OSA patients with CIBERSORT, and monocytes were found to be related with the remission of OSA and partially correlated with the hub genes identified. In conclusion, these key genes and immune infiltration may be of great importance in the remission of OSA and related research of these genes may provide a new therapeutic target for OSA in the future.

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