Improvement in Obstructive Sleep Apnea With Weight Loss is Dependent on Body Position During Sleep

There is currently only limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). The aim of our study is to identify genetic loci associated with OSA risk and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using FinnGen Study (217,955 individuals) with 16,761 OSA patients identified using nationwide health registries. We estimated 8.3% [0.06-0.11] heritability and identified five loci associated with OSA (P < 5.0x10^-8): rs4837016 near GTPase activating protein and VPS9 domains 1 (GAPVD1), rs10928560 near C-X-C motif chemokine receptor 4 (CXCR4), rs185932673 near Calcium/calmodulin-dependent protein kinase ID (CAMK1D) and rs9937053 near Fat mass and obesity-associated protein (FTO) - a variant previously associated with body mass index (BMI). In a BMI-adjusted analysis, an association was observed for rs10507084 near Rhabdomyosarcoma 2 associated transcript (RMST)/NEDD1 gamma-tubulin ring complex targeting factor (NEDD1). We found genetic correlations between OSA and BMI (rg=0.72 [0.62-0.83]) and with comorbidities including hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), stroke, depression, hypothyroidism, asthma and inflammatory rheumatic diseases (IRD) (rg > 0.30). Polygenic risk score (PRS) for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile and Mendelian randomization supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA and joint genetic basis between OSA and comorbidities.

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“…These findings are in line with the finding that weight loss is an important contributor of lowering AHI and the severity of OSA 39,40 .…”

Section: Discussionsupporting

confidence: 91%

Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

Strausz

Ruotsalainen

Ollila

et al. 2020

Preprint

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“…33 Furthermore, if residual POSA following alternative therapies can be simply diagnosed during treatment review studies, then there are also occasions where positional therapy may be successfully added in combination. 26 Weight loss, for example, frequently improves, but rarely cures OSA and leads to a greater improvement in the nonsupine AHI than supine AHI 34 opening up positional therapy for a range of patients. Similarly, detecting residual POSA may help dentists guide the titration of oral appliances for the treatment of OSA, identifying when OSA could be further resolved with the addition of position therapy, rather than risking long-term complications (eg, from excessive mandibular advancement) or accepting less than optimal outcomes.…”

Section: Discussionmentioning

confidence: 99%

<p>A comparison between auto-scored apnea-hypopnea index and oxygen desaturation index in the characterization of positional obstructive sleep apnea</p>

Levendowski

Hamilton

Louis

et al. 2019

NSS

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Objective: Evaluate the concordance between overall and positional oxygen desaturation indices (ODI) and apnea-hypopnea indices (AHI) according to two different definitions for positional obstructive sleep apnea (POSA). Methods: A total of 184 in-home polysomnograms were edited to simulate Level III home sleep apnea tests (HSAT) with the auto-scored AHI and ODI based on recording time. POSA was determined using 132 records with an AHI≥5 and at least 20 mins of recording time in both supine and non-supine positions. POSA was defined independently for the AHI and ODI based on ratios of overall/non-supine event/h ≥1.4 (O/NS) and supine/non-supine event/h≥2.0 (S/NS). Results: Correlation between the AHI and ODI was 0.97 overall, 0.94 for supine, and 0.96 for non-supine recording times (all p<0.001). For most records, differences between the AHI and ODI were small, with only 14% of the records having a AHI-ODI difference exceeding >5/hr, and 6% exceeding >10 events/hr. The positive and negative percent agreements were uniformly good to excellent across varying clinical POSA cutoffs; percent agreements (positive, negative) were: AHI≥5=0.99, 0.78; AHI≥10=0.96, 0.89; and AHI≥15=0.96, 0.89. Cohen's Kappa scores also showed substantial agreement for overall as well as supine and non-supine positions across varying clinical cutoffs of the AHI. Frequency of POSA was reproducibly uniform between 59% and 61% for both POSA criteria. When the O/NS and S/NS definitions conflicted in POSA characterization, O/NS was superior for identifying patients who might exhibit a greater response to supine restriction positional therapy. Conclusions: Auto-scored positional oximetry is a clinically viable alternative to an autoscored Level III HSAT AHI in the characterization of POSA based on a 3% desaturation.

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“…Many patients affected by OSA and SDB fail to resolve their sleep disorders with weight loss alone . Some patients affected by SDB fail to fit into a category of BMI‐defined obesity (BMI ≥30) so other clinically relevant factors such as allergies must be impacting their sleep quality . Traditionally, REM‐OSA has been diagnosed by looking at REM‐AHI values.…”

Section: Discussionmentioning

confidence: 99%

Clinical associations between allergies and rapid eye movement sleep disturbances

Berson

Klimczak

Prezio

et al. 2018

Int Forum Allergy Rhinol

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BackgroundAllergic rhinitis, an immunoglobulin E inflammatory condition including nasal congestion, obstruction, sneezing, pruritus, and fatigue symptoms, has significant impact on quality of life and impairs sleep. Sleep‐disordered breathing (SDB) patients often have normal all‐night apnea‐hypopnea (AHI) or respiratory‐disturbance (RDI) indices on polysomnography (PSG). We hypothesized that the rapid eye motion–respiratory disturbance index (REM‐RDI) may be a novel predictor of allergic status.MethodsA retrospective analysis of 100 patients compared REM‐RDI results in 67 allergen‐positive patients with 33 nonallergic patients who presented with nasal blockage. Subjects completed STOP‐Bang©, 22‐item Sino‐Nasal Outcome Test (SNOT‐22)©, and Epworth Sleepiness Scale© questionnaires and underwent skin‐prick testing (SPT) and PSGs including REM‐RDI values. Using multivariate logistic regression models, we evaluated relationships between allergic status and sleep parameters while controlling for possible confounders including body mass index (BMI).ResultsUsing REM‐RDI as the outcome of interest, allergen‐positive patients were 3.92 times more likely to have REM‐RDI values in a moderate/severe range (≥15 events/hour); and patients with moderate/severe REM‐RDI values were more likely to be allergen positive (p < 0.05). Allergic status was not significantly related to all‐night AHI, RDI, or REM‐AHI. BMI was not significantly related to REM‐RDI. STOP‐Bang© was related to allergy status (p = 0.02) and REM‐RDI (p < 0.01). Allergic patients had increased REM latency and less total amount of REM.ConclusionWe revealed significant bidirectional associations between allergen positivity and increased REM‐RDI values independent of BMI, AHI, RDI, and REM‐AHI. Allergic inflammation and REM‐RDI data may play important roles in diagnosing and treating fatigued SDB patients and as objective perioperative safety and outcomes measures.

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Improvement in Obstructive Sleep Apnea With Weight Loss is Dependent on Body Position During Sleep

Abstract: Following weight loss, a significant proportion (22%) of patients with obesity have normalization of the nonsupine AHI. For these patients, supine sleep avoidance may cure their OSA.

Cited by 40 publications

References 24 publications

Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

<p>A comparison between auto-scored apnea-hypopnea index and oxygen desaturation index in the characterization of positional obstructive sleep apnea</p>

Clinical associations between allergies and rapid eye movement sleep disturbances

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