Sleep Disordered Breathing, Obesity and Atrial Fibrillation: A Mendelian Randomisation Study.
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ABSTRACT:
SUBMITTER: Ardissino M
PROVIDER: S-EPMC8774383 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:An important consequence of sleep-disordered breathing (SDB) is excessive daytime sleepiness (EDS). EDS often predicts a favorable response to treatment of SDB, although in the setting of cardiovascular disease, particularly heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is another highly prevalent condition strongly associated with SDB. We sought to assess the relationship between EDS and SDB in patients with AF.We conducted a prospective study of 151 patients referred for direct current cardioversion for AF who also underwent sleep evaluation and nocturnal polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to polysomnography and considered positive if the score was ≥ 11. The apnea-hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of ≥ 5 events/h for the diagnosis of SDB.Among the study participants, mean age was 69.1 ± 11.7 years, mean BMI was 34.1 ± 8.4 kg/m(2), and 76% were men. The prevalence of SDB in this population was 81.4%, and 35% had EDS. The association between ESS score and AHI was low (R(2) = 0.014, P = .64). The sensitivity and specificity of the ESS for the detection of SDB in patients with AF were 32.2% and 54.5%, respectively.Despite a high prevalence of SDB in this population with AF, most patients do not report EDS. Furthermore, EDS does not appear to correlate with severity of SDB or to accurately predict the presence of SDB. Further research is needed to determine whether EDS affects the natural history of AF or modifies the response to SDB treatment.
| S-EPMC3318950 | biostudies-other
Project description:BackgroundThe occurrence of atrial fibrillation, circadian fluctuation in blood pressure, and oxygen desaturation at night is likely associated with the pathophysiology of wake-up stroke. Whether patients who experience wake-up strokes are candidates for thrombolysis treatment is a serious dilemma. The aim is to investigate the association between risk factors and wake-up stroke and to determine variations that are associated with the pathophysiology of wake-up stroke.MethodsFive major electronic databases were searched using a fitted search strategy to identify relevant studies. Odds ratios with 95% CIs were used to calculate estimates, and the Quality Assessment for Diagnostic Accuracy Studies-2 tool was used to conduct the assessment quality.ResultsA total of 29 studies were included in this meta-analysis. Hypertension is not associated with wake-up stroke (odds ratio, 1.14 [95% CI, 0.94-1.37]; P = .18). Atrial fibrillation is an independent risk factor to wake-up stroke, with a statistically significant difference (odds ratio, 1.28 [95% CI, 1.06-1.55]; P = .01). Subgroup analysis showed a different result in patients with sleep-disordered breathing, although no significant difference was assessed.ConclusionThis study revealed that atrial fibrillation is an independent risk factor for wake-up stroke and that patients with atrial fibrillation who also experience sleep-disordered breathing tend to have fewer wake-up strokes.
| S-EPMC10353276 | biostudies-literature
Project description:BackgroundSleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke.MethodsIn this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events.ResultsAmong 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]).ConclusionsComorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.
| S-EPMC10896199 | biostudies-literature
Project description:Electrocardiographic (ECG) markers of left atrial (LA) abnormalities have been linked to increased risk of atrial fibrillation (AF). Sleep disordered breathing (SDB) has been associated with increased risk of AF. We aimed to examine the association of ECG markers of LA abnormalities with SDB.1546 participants (mean age 67.2 years, 53.4% women, and 63.3% non-whites) from the Multi-Ethnic Study of Atherosclerosis Exam 5 Sleep ancillary study were included in this analysis. ECG markers of LA abnormalities (P wave terminal force in V1 (PTFV1), maximum P wave duration, PR interval and heart rate corrected PR interval) were measured from resting standard digital ECG tracings using standardized processing. Linear and logistic regression analyses were utilized to examine the cross-sectional associations of measures of SDB (apnea hypopnea index [AHI] and % time spent with oxygen saturation?<90% [%SpO290]) with each ECG marker. In a multivariable analysis adjusting for demographics, cardiovascular risk factors, and comorbidities, AHI was associated with greater PTFV1 but not with other ECG markers of LA abnormalities. A 1-SD increase of AHI (16.6/hr) was associated with higher levels of PTFV1 (175.1 µV.ms, 95% confidence interval [95%CI] 75.4, 274.7) and higher odds of abnormally elevated PTFV1 (?4000 µV.ms) (Odds Ratio: 1.21 [95%CI 1.05, 1.39]). No association was found between %SpO290 and ECG markers of LA abnormalities.Severity of SDB, as measured by AHI, is associated with subclinical LA disease, as indicated by PTFV1. PTFV1 may be an important ECG marker linking SDB and AF.
| S-EPMC6279118 | biostudies-literature
Project description:BackgroundSleep-disordered breathing (SDB) may contribute to development of stroke. However, findings are inconclusive. We investigated whether SDB-related symptoms are associated with incidence of stroke and its types in a general community sample of adult men and women as well as to perform Mendelian randomization (MR) analysis.MethodsWe used data from a cohort of 41,742 Swedish adults (56-94 years of age) who completed questionnaires regarding snoring, cessation of breathing, lifestyle and health characteristics. Participants were followed up for incident stroke and death over 8 years through linkage to the Swedish Registers. Hazard ratios, adjusted for potential confounders, were estimated by Cox proportional hazards regression. MR analyses were performed using single-nucleotide polymorphisms associated with sleep apnea at the genome-wide significance level and summary-level data for stroke and its subtypes from consortia and a meta-analysis of Genome-Wide Association Studies.ResultsIn the cohort study, symptoms of disturbing snoring and/or cessation of breathing were associated with increased risk of total stroke (hazard ratio 1.12, 95% confidence interval 1.02-1.24) and intracerebral hemorrhage (hazard ratio 1.59, 95% confidence interval 1.23-2.05) but not with ischemic stroke or subarachnoid hemorrhage. MR analyses showed no association of genetic liability to sleep apnea with the risk of overall stroke or any specific types of stroke or ischemic stroke subtypes.ConclusionsSDB-related symptoms were associated with increased risk of total stroke, specifically intracerebral hemorrhage, in the observational analyses but not in the MR analyses. There was limited evidence of an association of SDB with ischemic stroke and subarachnoid hemorrhage.
| S-EPMC9021054 | biostudies-literature
Project description:Objective:Individuals with multiple metabolic risk factors often experience concomitant sleep-disordered breathing (SDB). We aimed to determine the associations of SDB with individual components of metabolic syndrome independent of obesity. Methods:A cross-sectional study was conducted in 1137 employees aged 30-64 years. Apnea-hypopnea index (AHI) was assessed using a portable monitor for obstructive sleep apnea by admission. Of these, 451 participants took an oral glucose tolerance test to assess homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI). Results:The odds ratio (OR) of the highest category of the AHI (≥15 episodes per hour) compared to the lowest one (<5 episodes per hour) was significantly elevated for hypertension, for hypertriglyceridemia, and for low HDL-cholesterolemia when adjusted for age, sex, and alcohol and smoking status (p < 0.05). After further adjustment for body mass index (BMI) or waist circumference, the associations for hypertension still remained statistically significant (p < 0.05) while those for hypertriglyceridemia and low HDL-cholesterolemia were no longer significant. The association between higher insulin resistance as assessed by HOMA-IR and Matsuda ISI and higher categories of the AHI was also lost after adjustment for BMI. Conclusion:Obesity was a strong confounding factor in the association between SDB and most metabolic risk factors including insulin resistance, except for hypertension. Further longitudinal study is needed to examine the temporal or causal relationships between SDB and metabolic risk factors. This trial is registered with UMIN-CTR UMIN000028067.
| S-EPMC6217749 | biostudies-other
Project description:RationaleObesity increases the risk and severity of sleep-disordered breathing. The degree to which excess body weight contributes to blood oxygen desaturation during hypopneic and apneic events has not been comprehensively characterized.ObjectivesTo quantify the association between excess body weight and oxygen desaturation during sleep-disordered breathing.MethodsA total of 750 adult participants in the Wisconsin Sleep Cohort Study were assessed for body mass index (BMI) (kg/m(2)) and sleep-disordered breathing. The amount of Sa(O(2)), duration, and other characteristics of 37,473 observed breathing events were measured during polysomnography studies. A mixed-effects linear regression model estimated the association of blood oxygen desaturation with participant-level characteristics, including BMI, gender, and age, and event-level characteristics, including baseline Sa(O(2)), change in Vt, event duration, sleep state, and body position.Measurements and main resultsBMI was positively associated with oxygen desaturation severity independent of age, gender, sleeping position, baseline Sa(O(2)), and event duration. BMI interacted with sleep state such that BMI predicted greater desaturation in rapid eye movement (REM) sleep than in non-REM sleep. Each increment of 10 kg/m(2) BMI predicted a 1.0% (SE, 0.2%) greater mean blood oxygen desaturation for persons in REM sleep experiencing hypopnea events associated with 80% Vt reductions.ConclusionsExcess body weight is an important predictor of the severity of blood oxygen desaturation during apnea and hypopnea events, potentially exacerbating the impact of sleep-disordered breathing in obese patients.
| S-EPMC2778152 | biostudies-literature
Project description:Obesity leads to sleep-disordered breathing (SDB) manifested by recurrent upper airway obstructions termed obstructive sleep apnea (OSA) and carbon dioxide retention due to hypoventilation. The objective of this work was to characterize breathing during sleep in C57BL6/J mice with diet-induced obesity (DIO). Arterial blood gas was measured in nine obese and nine lean mice during wakefulness. Nine male mice with DIO and six lean male C57BL/6J mice were head mounted with electroencephalogram (EEG) and electromyogram (EMG) electrodes. Sleep recordings were performed in the whole body plethysmography chamber; upper airway obstruction was characterized by the presence of inspiratory flow limitation in which airflow plateaus with increases in inspiratory effort. Obese mice showed significantly lower pH and higher partial pressure of arterial CO2 (PaCO2) in arterial blood gas compared to lean mice, 7.35 ± 0.04 versus 7.46 ± 0.06 (p < 0.001) and 38 ± 8 mm Hg versus 30 ± 5 mm Hg (p < 0.001). Obese mice had similar levels of minute ventilation to lean mice during sleep and wakefulness, despite higher body weight and temperature, indicating an increase in the metabolic rate and hypoventilation. Obese mice also showed baseline hypoxemia with decreased mean oxyhemoglobin saturation across sleep/wake states. Obese mice had a higher prevalence of flow-limited breathing compared to lean mice during sleep. However, the oxygen desaturation index in lean and obese mice did not differ. We conclude that DIO in mice leads to hypoventilation. Obesity also increases the frequency of inspiratory limited breaths, but it does not translate into progression of OSA.
| S-EPMC6093346 | biostudies-literature
Project description:BackgroundAtrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR).Methods and findingsWeighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87-0.96, P = 2 × 10-4 and OR 0.94; 95% CI: 0.93-0.96, P = 2 × 10-19, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank.ConclusionsIn UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.
| S-EPMC8118296 | biostudies-literature
Project description:OBJECTIVE:The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. STUDY DESIGN:NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized level 3 home sleep test was performed between 6(0)-15(0) weeks' gestation (visit 1) and again between 22(0)-31(0) weeks' gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met "urgent referral" criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth. RESULTS:Objective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on 2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported in this methods article. CONCLUSION:The substudy was designed to address important questions regarding the relationship of sleep-disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health.
| S-EPMC4410772 | biostudies-literature