scholarly journals Sleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study

Genes ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Maddalena Ardissino ◽  
Rohin K. Reddy ◽  
Eric A. W. Slob ◽  
Kiran H. K. Patel ◽  
David K. Ryan ◽  
...  

It remains unclear whether the association between obstructive sleep apnoea (OSA), a form of sleep-disordered breathing (SDB), and atrial fibrillation (AF) is causal or mediated by shared co-morbidities such as obesity. Existing observational studies are conflicting and limited by confounding and reverse causality. We performed Mendelian randomisation (MR) to investigate the causal relationships between SDB, body mass index (BMI) and AF. Single-nucleotide polymorphisms associated with SDB (n = 29) and BMI (n = 453) were selected as instrumental variables to investigate the effects of SDB and BMI on AF, using genetic association data on 55,114 AF cases and 482,295 controls. Primary analysis was conducted using inverse-variance weighted MR. Higher genetically predicted SDB and BMI were associated with increased risk of AF (OR per log OR increase in snoring liability 2.09 (95% CI 1.10–3.98), p = 0.03; OR per 1-SD increase in BMI 1.33 (95% CI 1.24–1.42), p < 0.001). The association between SDB and AF was not observed in sensitivity analyses, whilst associations between BMI and AF remained consistent. Similarly, in multivariable MR, SDB was not associated with AF after adjusting for BMI (OR 0.68 (95% CI 0.42–1.10), p = 0.12). Higher BMI remained associated with increased risk of AF after adjusting for OSA (OR 1.40 (95% CI 1.30–1.51), p < 0.001). Elevated BMI appears causal for AF, independent of SDB. Our data suggest that the association between SDB, in general, and AF is attributable to mediation or confounding from obesity, though we cannot exclude that more severe SDB phenotypes (i.e., OSA) are causal for AF.

Author(s):  
Weiqi Chen ◽  
Xueli Cai ◽  
Hongyi Yan ◽  
Yuesong Pan

Background Obstructive sleep apnea (OSA) has shown to be associated with an increased risk of atrial fibrillation in observational studies. Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causal effect of OSA on atrial fibrillation. Methods and Results We used a 2‐sample Mendelian randomization (MR) method to evaluate the causal effect of OSA on atrial fibrillation. Summary data on genetic variant‐OSA association were obtained from a recently published genome‐wide association studies with up to 217 955 individuals and data on variant‐atrial fibrillation association from another genome‐wide association study with up to 1 030 836 individuals. Effect estimates were evaluated using inverse‐variance weighted method. Other MR analyses, including penalized inverse‐variance weighted, penalized robust inverse‐variance weighted, MR‐Egger, simple median, weighted median, weighted mode‐based estimate and Mendelian Randomization Pleiotropy Residual Sum and Outlier methods were performed in sensitivity analyses. The MR analyses in both the fixed‐effect and random‐effect inverse‐variance weighted models showed that genetically predicted OSA was associated with an increased risk of atrial fibrillation (odds ratio [OR], 1.21; 95% CI, 1.12–1.31, P <0.001; OR, 1.21; 95% CI, 1.11–1.32, P <0.001) using 5 single nucleotide polymorphisms as the instruments. MR‐Egger indicated no evidence of genetic pleiotropy (intercept, −0.014; 95% CI, −0.033 to 0.005, P =0.14). Results were robust using other MR methods in sensitivity analyses. Conclusions This MR analysis found that genetically predicted OSA had causal effect on an increased risk of atrial fibrillation.


2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Jian Zhao ◽  
Rachel Freathy ◽  
David Evans ◽  
Nicole Warrington ◽  
Claudia Langenberg ◽  
...  

Abstract Background It is suggested amino acids are critical for fetal growth, but analyses assessing causality are lacking. Mendelian randomisation (MR) can be used to examine causal effects under instrumental variable (IV) assumptions. Methods We conducted a two-sample MR study utilizing summary data from genome-wide association studies (GWAS) of amino acids (sample 1, n = 86,507) and of offspring birthweight (sample 2, combined UK Biobank and Early Growth Genetics Consortium, n = 406,063). Seventy-five independent single nucleotide polymorphisms (SNPs) robustly associated with 18 amino acids (p &lt; 4.9 × 10-10) were used as genetic instruments. Wald ratio and inverse variance weighted methods were used in MR main analysis. Sensitivity analyses were performed to explore IV assumption violations. To explore whether there was consistency between SNP-amino acid associations in pregnancy and in the GWAS, the latter were compared to associations in the Born in Bradford cohort. Results There was evidence of positive causal effects of maternal alanine (51.9 g birthweight increase per SD increase in amino acid level, 95% CI: 24.2, 79.5), glutamine (51.3 g, 95% CI: 33.5, 69.0), glycine (10.4 g, 95% CI: 1.3, 19.6) and serine (27.1 g, 95% CI: 11.2, 43.0) on birthweight and inverse causal effects of maternal isoleucine (-109.7 g, 95% CI: -194.6, -24.9) and histidine (-41.1 g, 95% CI: -78.5, -3.7) on birthweight. Sensitivity analyses to explore reverse causality and bias due to horizontal pleiotropy supported our findings. Conclusions Some maternal circulating amino acids have causal effects on birthweight. Key messages MR can be extended to probe effects of maternal nutrition on offspring development.


2017 ◽  
Vol 13 (3) ◽  
pp. 183 ◽  
Author(s):  
Mellar P. Davis, MD, FCCP, FAAHPM ◽  
Bertrand Behm, MD ◽  
Diwakar Balachandran, MD

Opioids adversely influence respiration in five distinct ways. Opioids reduce the respiratory rate, tidal volume, amplitude, reflex responses to hypercapnia and hypoxia, and arousability related necessary for respiratory adaptive responses. Opioids cause impairment of upper pharyngeal dilator muscles leading to obstructive apnea. Opioids cause complex sleep disordered breathing (SDB) consisting of central sleep apnea and obstructive sleep apnea. Clinically opioids worsen preexisting SDB. Recent studies have shown increased morbidity and mortality in patients receiving opioids for chronic noncancer pain and chronic obstructive pulmonary disease, which appear to be related to cardiovascular events, not overdose. Both patient populations are at risk for sleep disordered breathing and increased risk for adverse cardiovascular events on opioids for dyspnea or pain. This review discusses the influence of opioids on respiration and SDB and will review the adverse respiratory and cardiovascular effects of opioid use in at risk populations. Recommendations regarding management will follow as a summary.


2020 ◽  
Vol 17 ◽  
pp. 147997312092810
Author(s):  
Anna Khokhrina ◽  
Elena Andreeva ◽  
Jean-Marie Degryse

Sleep-disordered breathing (SDB) is a chronic condition characterized by repeated breathing pauses during sleep. The reported prevalence of SDB in the general population has increased over time. Furthermore, in the literature, a distinction is made between SDB, obstructive sleep apnea (OSA), and “OSA syndrome” (OSAS). Patients with SDB are at increased risk of comorbid cardiovascular diseases (CVDs). The aim of the ARKHsleep study was to assess the prevalence of SDB in general and of OSA and OSAS in particular. A total of 1050 participants aged 30–70 years, who were randomly selected from a population register, were evaluated for the probability of SDB using the Epworth Sleepiness Scale score and body mass index. Sleep was recorded for one night via home sleep apnea testing (Somnolter®). Medical conditions were determined from medical records. Additional data included background characteristics, anthropometric variables, blood pressure, and scores from four questionnaires. The survey sample consisted of 41.2% males and had a mean age of 53.1 ± 11.3 years. The prevalence of mild-to-severe, moderate-to-severe, and severe SDB was 48.9% [45.8–51.9], 18.1% [15.9–20.6], and 4.5% [3.2–5.8], respectively. Individuals reporting snoring or breathing pauses had a higher severity of SDB than individuals free of symptoms. The ARKHsleep study revealed a high burden of both SDB and CVD; however, more large-scale cohort studies and intervention studies are needed to better understand whether the early recognition and treatment of mild SDB with or without symptoms will improve cardiovascular prognosis and/or quality of life.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ghanshyam Palamaner Subash Shantha ◽  
Anita A Kumar ◽  
Lawrence J Cheskin ◽  
Samir B Pancholy

Introduction: Sleep disordered breathing (SDB) and obstructive sleep apnea (OSA) increase risk for multiple morbidities such as cardiovascular events, diabetes mellitus, and hypertension. Association between SDB and incident cancer is unclear and studies that assessed this association have yielded conflicting results. Hypothesis: We systematically reviewed the literature and pooled available evidence that has associated SDP and incident cancer. Methods: Medline, Embase, Cochrane central library, and electronic databases were searched for relevant studies. Studies were included if: 1) they studied patients with SDB, and 2) reported rates of incident cancer. We excluded studies that reported cancers involving head and neck as we suspected reverse causation, since head and neck cancers can lead to SDP. Data were pooled using a random-effects model. Results: From 3522 retrieved citations, 7 observational studies were included in the review. Of these, 4 studies, representing 48,152 patients with SDB and 87,849 patients without SDB, were included in the meta-analysis. In total 6931 incident cancer cases were reported (2813 in SDB group and 4118 in non-SDB group). In the pooled analysis, patients with SDB experienced higher odds of incident cancer (OR: 1.30, 95% CI: 1.06 - 1.60, P = 0.01, I 2 : 75%, 4 included studies) compared to those without SDB. Data from 2 studies that assessed patients with OSA, showed that OSA increased risk for incident cancer at 5 years follow-up (OR: 1.90, 95% CI: 1.46 - 2.45, P < 0.001, I 2 : 0%) and 8 years follow-up (OR: 1.54, 95% CI: 1.25 - 1.88, P < 0.001, I 2 : 0%). Also, cancer risk (OR: 1.28, 95% CI: 1.09 - 1.51, P = 0.003, I 2 : 21%, 2 studies) and cancer mortality (OR: 1.84, 95% CI: 1.32 - 2.56, P = 0.003, I 2 : 0%, 2 studies) was significant only in patients with severe OSA [apnea-hypopnea index (AHI) > 30] and not in patients with mild to moderate OSA (AHI < 30). Factors namely; obesity, type of cancer, age and gender did not account for between study heterogeneity. Conclusions: SDB and OSA are associated with incident cancer. Though our study did not support the role of obesity in this association, strong mechanistic link exists, associating SDB, obesity and cancer. Future studies should assess the association between SDB and organ specific cancers.


Author(s):  
Juliana Alves Sousa Caixeta ◽  
Jessica Caixeta Silva Sampaio ◽  
Vanessa Vaz Costa ◽  
Isadora Milhomem Bruno da Silveira ◽  
Carolina Ribeiro Fernandes de Oliveira ◽  
...  

Abstract Introduction Adenotonsillectomy is the first-line treatment for obstructive sleep apnea secondary to adenotonsillar hypertrophy in children. The physical benefits of this surgery are well known as well as its impact on the quality of life (QoL), mainly according to short-term evaluations. However, the long-term effects of this surgery are still unclear. Objective To evaluate the long-term impact of adenotonsillectomy on the QoL of children with sleep-disordered breathing (SDB). Method This was a prospective non-controlled study. Children between 3 and 13 years of age with symptoms of SDB for whom adenotonsillectomy had been indicated were included. Children with comorbities were excluded. Quality of life was evaluated using the obstructive sleep apnea questionnaire (OSA-18), which was completed prior to, 10 days, 6 months, 12 months and, at least, 18 months after the procedure. For statistical analysis, p-values lower than 0.05 were defined as statistically significant. Results A total of 31 patients were enrolled in the study. The average age was 5.2 years, and 16 patients were male. The OSA-18 scores improved after the procedure in all domains, and this result was maintained until the last evaluation, done 22 ± 3 months after the procedure. Improvement in each domain was not superior to achieved in other domains. No correlation was found between tonsil or adenoid size and OSA-18 scores. Conclusion This is the largest prospective study that evaluated the long-term effects of the surgery on the QoL of children with SDB using the OSA-18. Our results show adenotonsillectomy has a positive impact in children's QoL.


BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e044499
Author(s):  
Fanny Bertelli ◽  
Carey Meredith Suehs ◽  
Jean Pierre Mallet ◽  
Marie Caroline Rotty ◽  
Jean Louis Pepin ◽  
...  

Introduction To date, continuous positive airway pressure (CPAP) remains the cornerstone of obstructive sleep apnoea treatment. CPAP data describing residual sleep-disordered breathing events (ie, the CPAP-measured apnoea–hypopnoea indices (AHI-CPAPflow)) is difficult to interpret because it is an entirely different metric than the polysomnography (PSG) measured AHI gold standard (AHI-PSGgold). Moreover, manufacturer definitions for apnoea and hypopnoea are not only different from those recommended for PSG scoring, but also different between manufacturers. In the context of CPAP initiation and widespread telemedicine at home to facilitate sleep apnoea care, there is a need for concrete evidence that AHI-CPAPflow can be used as a surrogate for AHI-PSGgold. Methods and analysis No published systematic review and meta-analysis (SRMA) has compared the accuracy of AHI-CPAPflow against AHI-PSGgold and the primary objective of this study is therefore to do so using published data. The secondary objectives are to similarly evaluate other sleep disordered breathing indices and to perform subgroup analyses focusing on the inclusion/exclusion of central apnoea patients, body mass index levels, CPAP device brands, pressure titration modes, use of a predetermined and fixed pressure level or not, and the impact of a 4% PSG desaturation criteria versus 3% PSG on accuracy. The Preferred Reporting Items for SRMA protocols statement guided study design. Randomised controlled trials and observational studies of adult patients (≥18 years old) treated by a CPAP device will be included. The CPAP intervention and PSG comparator must be performed synchronously. PSGs must be scored manually and follow the American Academy of Sleep Medicine guidelines (2007 AASM criteria or more recent). To assess the risk of bias in each study, the Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used. Ethics and dissemination This protocol received ethics committee approval on 16 July 2020 (IRB_MTP_2020_07_2020000404) and results will be disseminated via peer-reviewed publications. PROSPERO/Trial registration numbers CRD42020159914/NCT04526366; Pre-results


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A224-A225
Author(s):  
Fayruz Araji ◽  
Cephas Mujuruki ◽  
Brian Ku ◽  
Elisa Basora-Rovira ◽  
Anna Wani

Abstract Introduction Achondroplasia (ACH) occurs approximately 1 in 20,000–30,000 live births. They are prone to sleep disordered breathing specifically due to the upper airway stenosis, enlarged head circumference, combined with hypotonia and limited chest wall size associated with scoliosis at times. The co-occurrence of sleep apnea is well established and can aide in the decision for surgical intervention, however it is unclear at what age children should be evaluated for sleep apnea. Screening is often delayed as during the daytime there is no obvious gas exchange abnormalities. Due to the rareness of this disease, large studies are not available, limiting the data for discussion and analysis to develop guidelines on ideal screening age for sleep disordered breathing in children with ACH. Methods The primary aim of this study is to ascertain the presence of sleep disorder breathing and demographics of children with ACH at time of first polysomnogram (PSG) completed at one of the largest pediatric sleep lab in the country. The secondary aim of the study is to identify whether subsequent polysomnograms were completed if surgical interventions occurred and how the studies differed over time with and without intervention. Retrospective review of the PSGs from patients with ACH, completed from 2017–2019 at the Children’s Sleep Disorders Center in Dallas, TX. Clinical data, demographics, PSG findings and occurrence of interventions were collected. Results Twenty-seven patients with the diagnosis of ACH met criteria. The average age at the time of their first diagnostic PSG was at 31.6 months of age (2.7 years), of those patients 85% had obstructive sleep apnea (OSA),51% had hypoxemia and 18% had hypercapnia by their first diagnostic sleep study. Of those with OSA, 50% were severe. Majority were females, 55%. Most of our patients were Hispanic (14%), Caucasian (9%), Asian (2%), Other (2%), Black (0%). Each patient had an average of 1.9 PSGs completed. Conclusion Our findings can help create a foundation for discussion of screening guidelines. These guidelines will serve to guide primary care physicians to direct these patients to an early diagnosis and treatment of sleep disordered breathing. Support (if any):


2021 ◽  
pp. 019459982199338
Author(s):  
Flora Yan ◽  
Dylan A. Levy ◽  
Chun-Che Wen ◽  
Cathy L. Melvin ◽  
Marvella E. Ford ◽  
...  

Objective To assess the impact of rural-urban residence on children with obstructive sleep-disordered breathing (SDB) who were candidates for tonsillectomy with or without adenoidectomy (TA). Study Design Retrospective cohort study. Setting Tertiary children’s hospital. Methods A cohort of otherwise healthy children aged 2 to 18 years with a diagnosis of obstructive SDB between April 2016 and December 2018 who were recommended TA were included. Rural-urban designation was defined by ZIP code approximation of rural-urban commuting area codes. The main outcome was association of rurality with time to TA and loss to follow-up using Cox and logistic regression analyses. Results In total, 213 patients were included (mean age 6 ± 2.9 years, 117 [55%] male, 69 [32%] rural dwelling). Rural-dwelling children were more often insured by Medicaid than private insurance ( P < .001) and had a median driving distance of 74.8 vs 16.8 miles ( P < .001) compared to urban-dwelling patients. The majority (94.9%) eventually underwent recommended TA once evaluated by an otolaryngologist. Multivariable logistic regression analysis did not reveal any significant predictors for loss to follow-up in receiving TA. Cox regression analysis that adjusted for age, sex, insurance, and race showed that rural-dwelling patients had a 30% reduction in receipt of TA over time as compared to urban-dwelling patients (hazard ratio, 0.7; 95% CI, 0.50-0.99). Conclusion Rural-dwelling patients experienced longer wait times and driving distance to TA. This study suggests that rurality should be considered a potential barrier to surgical intervention and highlights the need to further investigate geographic access as an important determinant of care in pediatric SDB.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A322-A323
Author(s):  
Rahul Dasgupta ◽  
Sonja Schütz ◽  
Tiffany Braley

Abstract Introduction Sleep-disordered breathing is common in persons with multiple sclerosis (PwMS), and may contribute to debilitating fatigue and other chronic MS symptoms. The majority of research to date on SDB in MS has focused on the prevalence and consequences of obstructive sleep apnea; however, PwMS may also be at increased risk for central sleep apnea (CSA), and the utility of methods to assess CSA in PwMS warrant further exploration. We present a patient with secondary progressive multiple sclerosis who was found to have severe central sleep apnea on WatchPAT testing. Report of case(s) A 61 year-old female with a past medical history of secondary progressive multiple sclerosis presented with complaints of fragmented sleep. MRI of the brain, cervical spine, and thoracic spine showed numerous demyelinating lesions in the brain, brainstem, cervical, and thoracic spinal cord. Upon presentation, the patient noted snoring, witnessed apneas, and daytime sleepiness. WatchPAT demonstrated severe sleep apnea, with a pAHI of 63.3, and a minimum oxygen saturation of 90%. The majority of the scored events were non-obstructive in nature (73.1% of all scored events), and occurred intermittently in a periodic fashion. Conclusion The differential diagnosis of fatigue in PwMS should include sleep-disordered breathing, including both obstructive and central forms of sleep apnea. Demyelinating lesions in the brainstem (which may contribute to impairment of motor and sensory networks that control airway patency and respiratory drive), and progressive forms of MS, have been linked to both OSA and CSA. The present data illustrate this relationship in a person with progressive MS, and offer support for the WatchPAT as a cost-effective means to evaluate for both OSA and CSA in PwMS, while reducing patient burden. PwMS may be at increased risk for CSA. Careful clinical consideration should be given to ordering appropriate sleep testing to differentiate central from obstructive sleep apnea in PwMS, particularly for patients with demyelinating lesions in the brainstem. Support (if any) 1. Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med. 2014 Feb 15;10(2):155–62. doi: 10.5664/jcsm.3442. PMID: 24532998; PMCID: PMC3899317.


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