Allgauer, Chieko

INTRODUCTION: The increased likelihood of adverse cardiovascular events (CVE) shortly after awakening has been partially attributed to low nitric oxide (NO) production in the early morning. Thus, increasing early morning NO levels to improve vascular function could reduce adverse CVE incidence, especially among older adults as total NO production declines with aging. The increased adverse CVE among post-menopausal women (PMW) are likely due to a steeper decline in their vascular function. As inorganic nitrate increases circulating NO levels for up to 12hrs, our primary hypothesis was to determine if nocturnal inorganic nitrate supplementation improves early morning vascular function relative to a placebo in eight generally healthy adults (6F, 37±5yrs, 26.9±1.8kg/m 2 ). Our secondary hypothesis was that PMW (n=3, 27.1±4.3kg/m 2 ), identified by their age (71±2yrs) and follicle-stimulating hormone levels (72.3±8.0mIU/mL), would show greater improvements in their vascular function compared to younger participants (n=5, 3F, 28±2yrs, 26.8±2.0kg/m 2 ). METHODS: Written informed consent was obtained from all participants before data collection. Participants completed three overnight study visits: Visit 1 was for acclimation with vascular function assessments occurring during Visits 2 and 3. During the latter visits, participants consumed beetroot juice with (6.45mmol) or devoid of (0mmol) inorganic nitrate at 2200 in randomized, cross-over fashion followed by vascular function assessments post-awakening (0630-0800) while participants were supine. Vascular assessments consisted of brachial blood pressure, aortic augmentation index (AIx), carotid-femoral pulse wave velocity (cfPWV), and endothelial function (FMD). Data were compared using a paired-samples t-test (α<0.05). RESULTS: Systolic (125±4 vs. 126±6mmHg, p=0.35) and diastolic (71±2 vs. 72±2mmHg, p=0.32) blood pressure were similar the morning after nitrate and placebo. Additionally, AIx (31±5 vs. 33±6%, p=0.29) and FMD (n=7, 8.8±2.0 vs. 7.6±1.7%, p=0.25) were not different the morning after nitrate and placebo consumption. However, cfPWV was lower the morning following nitrate consumption relative to the placebo (6.3±0.5 vs. 6.9±0.6m/s, p=0.01). A sub-group analysis of PMW showed that both systolic (132±6 vs. 139±9mmHg, p=0.18) and diastolic (70±3 vs. 75±2mmHg, p=0.09) blood pressure tended to be lower following nitrate relative to the placebo whereas AIx (46±1 vs. 50±5%, p=0.31) and FMD (n=2, 8.5±2.7 vs. 6.9±1.6%, p=0.78) did not differ; however, cfPWV was lower the morning after nitrate consumption (7.4±0.9 vs. 8.4±1.1m/s, p=0.02) in PMW but not in the younger participants (5.6±0.4 vs. 6.0±0.3m/s, p=0.23). CONCLUSION: Acute nocturnal inorganic nitrate supplementation lowers aortic stiffness in the early morning, especially among PMW. Although the differences in systolic (7mmHg) and diastolic blood pressure (5mmHg) were not statistically significant, they remain clinically meaningful due to their magnitude. This may suggest a role for nocturnal nitrate supplementation in reducing early-morning adverse CVE among PMW. AHA 24POST1241616 (IMG), NIH K12 AR084222 (JMB), Sleep Research Society 038-JP-23 (JMB), and a grant from Sleep Number Corporation to Mayo Clinic for studies in Aging. This abstract was presented at the American Physiology Summit 2025 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.

Somali Americans, originating from East Africa, are a fast-growing minority in the United States. Emerging data suggest Somali individuals exhibit increased cardiovascular (CV) risk compared to non-Hispanic White adults. Previous data from our laboratory demonstrated elevated ambulatory arterial stiffness in Somali Americans, as derived from 24-hour blood pressure monitoring. We sought to confirm these vascular stiffness findings via gold-standard applanation tonometry and examine potential sex differences, given that females of African ancestry are at elevated risk of CV disease (CVD). We therefore examined aortic hemodynamics and carotid-femoral pulse wave velocity in male and female Somali Americans. We hypothesized that female Somali Americans would present with greater aortic wave reflection and arterial stiffness compared to males. We further examined the accuracy of prediction of aortic wave reflection from a predominantly White population, when applied to the Somali American population. We utilized applanation tonometry to quantify arterial stiffness in 24 female (age: 27±10 years, BMI: 27±6 kg/m 2 ) and 19 male (age: 22±6 years, BMI: 27±5 kg/m 2 ) Somali Americans without CVD. Each participant arrived in the laboratory at Mayo Clinic, fasted for at least three hours, and did not consume caffeine or exercise for at least 12 hours prior to testing. After 15 minutes of supine rest, duplicate recordings of aortic blood pressure and augmentation index (AIx) were obtained via pulse wave analysis. Similarly, aortic stiffness was quantified via duplicate carotid-femoral pulse wave velocity recordings. Statistical analysis included independent samples t-tests to test for sex differences in aortic hemodynamics, and paired samples t-tests to determine differences between estimated and obtained AIx (α≤0.05). Aortic systolic arterial pressure (111±11 vs. 108±7 mmHg, p=0.295) was similar between female and male Somali Americans. Aortic diastolic arterial pressure (75±7 vs. 67±7 mmHg, p<0.001) and heart rate (67±9 vs. 57±7 beats/min, p<0.001) were higher in female Somali adults. Similarly, AIx (28±14 vs. 19±12%, p=0.045) and AIx normalized to 75 heart beats/minute (24±13 vs. 10±13%, p=0.001) were higher in female Somali Americans. Carotid-femoral pulse wave velocity (5.4±0.9 vs. 5.5±0.8 m/s, p=0.661) was similar between sexes. Estimated AIx (corrected for sex, age, height, and resting heart rate) was markedly lower than observed AIx in both female (13±7 vs. 28±14%, p<0.001) and male (6±5 vs. 19±12%, p<0.001) Somali Americans. These findings, obtained in young, healthy Somali adults are suggestive of elevated CVD risk, evident at an early age. These data are particularly concerning regarding vascular dysfunction in Somali females and suggest that prediction models for arterial stiffness should factor in race to optimize performance. Future work into mechanisms underlying vascular dysfunction in Somali Americans is warranted. Sleep Number Grant to Mayo Clinic and by NIH R01-HL160619, R01-HL169320, T32-DK007013, K12 AR084222, and AHA 24POST1241616. This abstract was presented at the American Physiology Summit 2025 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 Poor sleep quality is bidirectionally associated with cardiovascular and neurocognitive disorders. Preclinical data implicate nitric oxide (NO) in the onset, and maintenance, of sleep. Acute inorganic nitrate supplementation increases NO bioavailability via serial reduction for &gt;12hrs. We tested if objective (Aim 1) or subjective (Aim 2) sleep quality was better following acute, pre-sleep nitrate supplementation relative to a placebo. Methods Seven non-shift working adults (4F/3M, 40±8yrs, 25.8±1.6kg/m2) with no history of sleep, cardiovascular, or neurocognitive disorders completed three overnight polysomnography (PSG) visits with time in bed standardized to 2200-0600hrs. Visit 1 was for acclimation and screening for sleep-disordered breathing. On Visits 2 and 3, participants consumed beetroot juice containing (6.45mmol) or devoid of (0mmol) inorganic nitrate at 2200 using a randomized, cross-over study design. PSG-derived outcomes included slow-wave (SWS) and rapid eye-movement (REM) sleep, sleep efficiency, and wake after sleep onset (WASO). Subjective sleep quality assessments were administered in-laboratory including a 0-10 scale, the Stanford Sleepiness Scale (SSS), and performance with mental arithmetic shortly after awakening. Results No participant demonstrated evidence for sleep-disordered breathing (apnea-hypopnea index = 1.7±0.9events/hr). Total sleep time (TST, 434±17 vs. 412±19min), sleep efficiency (89±3 vs. 85±4%), as well as SWS duration (75±10 vs. 66±9min) and percent of TST (17±2 vs. 16±2%) were higher after nitrate relative to the placebo (p&lt; 0.05 for all). WASO (47±16 vs. 62±19min, p&lt; 0.05) was lower after nitrate versus placebo and no differences were seen in REM sleep duration (131±23 vs. 117±12min, p=0.45) nor percent of TST (30±5 vs. 29±3%, p=0.80). Neither the 0-10 scale (6.7±0.5 vs. 6.8±0.6units, p=0.84), SSS (2.6±0.4 vs. 2.5±0.3units, p=0.68), or arithmetic performance (82±3 vs. 81±5% correct, p=0.85) differed post-nitrate compared to post-placebo. Conclusion These data suggest that acutely increasing nocturnal NO levels via pre-sleep inorganic nitrate supplementation improves objective indices of sleep quality in healthy adults. However, greater amounts of nitrate or prolonged supplementation (weeks) may be needed to improve perceived sleep quality. Support (if any) The National Institutes of Health (K12 AR084222 to JMB, R01s HL160619 and HL65176 to VKS), Sleep Research Society Foundation (CDA 038-JP-23 to JMB), and the American Heart Association (24POST1241616 to IMG).

Patients with obstructive sleep apnea (OSA) have increased risk for cardiovascular diseases. Data from the Atherosclerosis Risk in the Communities and Sleep Heart Health Study suggest that OSA is more deleterious to females versus males, although mechanistic data are lacking. Estimates of central (aortic) blood pressure (BP) are superior in predicting future cardiovascular events than traditional brachial BP measurements. While patients with OSA have altered central hemodynamics (e.g., higher aortic pulse wave velocity; PWV), potential sex differences are unexplored. We tested the hypothesis that females with OSA (n=7, 50±3yrs, 35.1±1.9kg/m2, 22.2±7.6 events/hr) have worse central hemodynamics than males with OSA (n=9, 47±3yrs, 35.0±1.4kg/m2, 31.7±6.2 events/hr). Data collection consisted of an overnight sleep study (polysomnography) to identify the presence, and characterize the severity, of OSA via the apnea-hypopnea index (AHI). Then, duplicate measures of central (aortic) and peripheral (brachial) BP, as well as central artery stiffness (PWV) and wave reflection (AIx), were made in the morning after ≥15min of quiet, supine rest. Additional hemodynamic measurements were made if data differed by ≥2% (AIx) or ≥0.5m/s (PWV). Data that met these criteria were averaged and used for analysis. Comparisons were made using two-tailed, independent samples t-tests or nonparametric Mann-Whitney Rank Sum tests, as indicated. No differences were observed in age (p=0.44), body mass index (p=0.96), nor AHI (p=1.00) between sexes. Similarly, no sex differences were observed in brachial systolic (female vs. male: 129±7 vs. 134±8mmHg, p=0.83), diastolic (77±5 vs. 85±4mmHg, p=0.26), or mean BP (96±6 vs. 101±5mmHg, p=0.45). Similarly, central systolic (122±6 vs. 125±7mmHg, p=0.96), diastolic (78±5 vs. 86±4mmHg, p=0.25), and augmentation (21±2 vs. 15±2mmHg, p=0.07) BP did not differ between sexes. Resting heart rate was also comparable between groups (67±3 vs. 65±2bpm, p=0.64). However, AIx (AIx; 42±3 vs. 35±4%) and AIx normalized to a heart rate of 75bpm (42±3 vs. 30±3%) were higher in females with OSA relative to males with OSA (p<0.05 for both). Interestingly, the forward (30±3 vs. 28±2mmHg, p=0.63) and reflected (20±2 vs. 18±2mmHg, p=0.44) pulse heights, as well as PWV (7.3±0.6 vs. 7.4±0.6m/s, p=0.85), were similar between groups. Our data indicate that despite a trend towards higher BP in males with OSA (~5mmHg) that may be clinically, though not statistically different, females with OSA have a higher AIx. As AIx is positively associated with left ventricular hypertrophy, these data also suggest that altered central (aortic) hemodynamics may contribute to the sex differences in cardiovascular risk with OSA. This work was supported by the National Institutes of Health T32-HL007111 and U54AG044170 (JMB), HL065176 (PS and VKS), and HL134885 (VKS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.