Somers, Virend

Background: Sleep regularity is emerging as an independent determinant of health. Multiple studies suggest a link between increased variability in sleep duration and timing and adverse cardiovascular, metabolic, and cognitive outcomes. There is, however, a lack of data on the implications of sleep regularity for aerobic capacity and physical endurance, particularly in patients with established cardiovascular disease. This study seeks to investigate the influence of irregularity in sleep duration on functional capacity in patients with coronary artery disease (CAD) undergoing cardiac rehabilitation (CR). Methods: We recruited a sample of patients with CAD who were referred to CR at Mayo Clinic Rochester. Participants completed a 6-minute walk test (6MWT) upon enrollment into CR. 6MWT variables included distance walked (meters), predicted distance walked (percentage) and estimated metabolic equivalents (METs). 24-hour objective sleep quality and quantity were assessed over a 7-day period by wrist actigraphy. Average standard deviation (SD) of sleep duration was used to define sleep regularity, with SD >60 minutes indicating irregular sleep. Chi-square test, independent samples t-test, and linear regression were used for statistical analysis. Results: Twenty-eight participants with valid actigraphy and 6MWT were included in this analysis (eight females; mean age 67.4 ± 11.6 years; body mass index 31.1 ± 5.8 kg/m 2 ). The average total sleep time was 7.1 ± 1.2 hours, and 10 participants (35.7%) exhibited sleep duration SD >60 minutes. Demographic, clinical and sleep characteristics were comparable between the regular and irregular sleep groups. Compared to patients with regular sleep, those with irregular sleep had poorer 6MWT, with shorter distance walked (406.2 ± 81.2 meters vs 338.8 ± 80.7 meters; p = 0.045), lower % of predicted distance walked (87.1 ± 18.7% vs 69.2 ± 11.4%; p = 0.011), and lower METS (2.99 ± 0.36 vs 2.63 ± 0.38; p = 0.022). Irregular sleep remained significantly associated with performance at the 6MWT after taking into account age and sex, with patients walking 14.4 meters fewer with every 10-minute increase in sleep variability (95% CI -28.1, -0.7; p 0.041). Conclusions: Increased day-to-day fluctuation in sleep duration is associated with reduced exercise capacity in patients with CAD undergoing CR. These findings add to the mounting body of evidence linking irregular sleep patterns to heightened cardiovascular risk, and support the integration of sleep monitoring in the CR practice to enhance risk stratification and outcome prediction. Funding Source: Sleep Number Corp. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Abstract Introduction AD109, an investigational oral anti-apneic neuromuscular modulator, combines in one tablet the novel antimuscarinic, aroxybutynin (2.5 mg), with the selective norepinephrine reuptake inhibitor, atomoxetine (75 mg). AD109 significantly improved the apnea-hypopnea index and oxygenation vs placebo (PBO) in two phase 3 clinical trials in OSA. This exploratory analysis evaluated concomitant administration of AD109 with glucagon-like peptide-1 receptor agonists (GLP-1 RA) on weight change in OSA. Methods SynAIRgy (NCT05813275; N=646) and LunAIRo (NCT05811247; N=660) were randomized, double-blinded, PBO-controlled, parallel-arm phase 3 trials of AD109 vs PBO in adults with mild-to-severe OSA (AHI >5) who failed or refused positive airway pressure therapy. Participants must have had a body mass index (BMI) 18.5–40 kg/m2 for males / 18.5–42 kg/m2 for females. Participants receiving GLP-1 RA for diabetes were permitted. Body weight was assessed throughout the trials. Results One-hundred and six participants were enrolled in the phase 3 trials taking a GLP-1 RA for diabetes (PBO+GLP-1 RA: n=48; AD109+GLP-1 RA: n=58). In participants receiving a GLP-1 RA with baseline BMI < 30, AD109 reduced weight by 2.7% (vs PBO: -1.4%, P=0.08) and 0.5% (vs PBO: 2.3%, P=0.60) at Week 26 and Week 51, respectively. In participants receiving a GLP-1 RA with baseline BMI 30 to 34.9, AD109 reduced weight by 0.9% (vs PBO: 1.2%, P=0.84) and 2.5% (vs PBO: 3.3%, P=0.85) at Week 26 and Week 51, respectively. In participants receiving a GLP-1 RA with baseline BMI ≥35, AD109 reduced weight by 5.5% (vs PBO: 0.9%, P=0.02) and 11.5% (vs PBO: 3.8%, P=0.04) at Week 26 and Week 51, respectively. Participants not receiving GLP-1 RA (n=979) showed smaller weight reductions across BMI classes; in participants with BMI ≥35, AD109 reduced weight by 1.4% (vs PBO: 0.2%, P=0.002) and 2.8% (vs PBO: 1.4%, P=0.19) at Week 26 and Week 51, respectively. Conclusion In this exploratory analysis using pooled data from SynAIRgy and LunAIRo, results indicate that participants with a baseline BMI ≥35 receiving AD109+GLP-1 RA experienced progressively greater weight loss over time relative to GLP-1 RA alone. Future studies are needed to further evaluate concomitant administration of AD109+GLP-1 RA in OSA. Support (if any) These studies were supported by Apnimed, Inc.

Abstract Purpose: Cardiovascular health disparities are present in African Americans, but it remains unknown whether this phenomenon affect Somali Americans. Study of Somali Americans is warranted due to distinct genetic and cultural differences from African Americans of western African ancestry. Orthostatic hemodynamic responses have implications for cardiovascular risk, especially among African American females. We sought to examine race and sex differences in systolic (SAP) and diastolic (DAP) arterial pressure and heart rate (HR) responsiveness to standing. We hypothesized that SAP, DAP, and HR change from supine to standing position would be higher in Somali Americans. Methods: We studied blood pressure and HR responsiveness in 139 (70 Somali; age: 29±10 years, 69 White; age: 31±9 years) participants. Supine SAP, DAP, and HR were measured after at least five minutes of supine rest, and again after one minute of standing. SAP, DAP, and HR change was compared between groups. Results: ΔSAP and ΔDAP were similar between groups (race × sex: p>0.05). However, HR responsiveness to orthostasis varied between race and sex comparisons (race×sex: p=0.011). Somali females exhibited an augmented HR response to orthostasis compared to White females (Δ19±13 vs. 11±9 beats/min, p=0.005) and Somali males (Δ19±13 vs. 12±9 beats/min, p=0.020). Conclusion: ΔHR to standing is augmented in young female Somali Americans. These findings highlight an early potential impairment in hemodynamic regulation that may heighten future cardiovascular risk. Further work is warranted to identify the potential autonomic nervous system underpinnings that may contribute to potentiated orthostatic responses and cardiovascular risk in Somali American females. Clinical Trial Registration: www.clinicaltrials.gov; unique identifier, NCT04124848; NCT05411029; NCT03308578.

Excessive daytime sleepiness (EDS) is classically viewed as a consequence of insufficient sleep or a symptom of sleep disorders. Epidemiological and clinical evidence have shown that patients reporting EDS in tandem with sleep disorders (e.g., obstructive sleep apnoea) are at greater cardiovascular risk than non-sleepy patients. While this may simply be attributable to EDS being present in patients with a more severe condition, treatment of sleep disorders does not consistently alleviate EDS, indicating potential aetiological differences. Moreover, not all patients with sleep disorders report EDS, and daytime sleepiness may be present even in the absence of any identifiable sleep disorder; thus, EDS could represent an independent pathophysiology. The purpose of this review is twofold: first, to highlight evidence that EDS increases cardiovascular risk in the presence of sleep disorders such as obstructive sleep apnoea, narcolepsy and idiopathic hypersomnia and second, to propose the notion that EDS may also increase cardiovascular risk in the absence of known sleep disorders, as supported by some epidemiological and observational data. We further highlight preliminary evidence suggesting systemic inflammation, which could be attributable to dysfunction of the gut microbiome and adipose tissue, as well as deleterious epigenetic changes, may promote EDS while also increasing cardiovascular risk; however, these pathways may be reciprocal and/or circumstantial. Additionally, gaps within the literature are noted followed by directions for future research.