Bock, Joshua M.

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.

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.

Patients with obstructive sleep apnea (OSA) have a heightened risk of developing cardiovascular diseases, namely hypertension. While seminal evidence indicates a causal role for sympathetic nerve activity in the hypertensive phenotype commonly observed in patients with OSA, no studies have investigated potential sex differences in the sympathetic regulation of blood pressure in this population. Supporting this exploration are large-scale observational data, as well as controlled interventional studies in healthy adults, indicating that sleep disruption increases blood pressure to a greater extent in females relative to males. Furthermore, females with severe OSA demonstrate a more pronounced hypoxic burden (i.e., disease severity) during rapid eye movement sleep when sympathetic nerve activity is greatest. These findings would suggest that females are at greater risk for the hemodynamic consequences of OSA and related sleep disruption. Accordingly, the purpose of this review is three-fold: (1) to review the literature linking sympathetic nerve activity to hypertension in OSA, (2) to highlight recent experimental data supporting the hypothesis of sex differences in the regulation of sympathetic nerve activity in OSA, and (3) to discuss the potential sex differences in peripheral adrenergic signaling that may contribute to, or offset, cardiovascular risk in patients with OSA.

Cardiovascular health disparities are present in several minority racial and ethnic groups including African Americans, who exhibit an increased risk of hypertension compared to non-Hispanic Whites. Somali Americans, a subgroup of African Americans of East African origins, exhibit high rates of diabetes and obesity, conditions often comorbid with impaired blood pressure (BP) regulation. Importantly, it remains unknown whether the disparate cardiovascular risk profile, namely poor nocturnal BP regulation, manifested in African Americans can be applied to Somali Americans. We therefore examined 24-hour BP patterns in Somali Americans compared to White control participants. We hypothesized that Somali Americans would present with heightened nocturnal BP and heart rate (HR). We utilized ambulatory blood pressure monitoring (ABPM) to quantify 24-hour BP patterns in 25 Somali (10 female, 15 male; age: 34 ± 3 years; BMI: 27 ± 1 kg/m2) and 25 White (13 female, 12 male; age: 38 ± 3 years; BMI: 27 ± 1 kg/m2) individuals. Each ABPM recorded a BP reading every 20 minutes throughout the 24-hour period. Subjects were instructed to abstain from caffeine, alcohol, and vigorous exercise during the recording period. From the 24-hour recording, an ambulatory arterial stiffness index (AASI) was calculated as 1 minus the regression slope of systolic (SAP) and diastolic (DAP) arterial pressure. SAP, DAP, and HR obtained between 12:00am and 6:00am were averaged to compute nocturnal means. BP and HR dipping was determined as the percent change between daytime and nocturnal BP and HR. Statistical analysis included independent samples t-tests to determine differences in BP and HR between racial groups (i.e., Somali vs. White). Nocturnal SAP (105 ± 2 vs. 106 ± 3 mmHg, p = 0.364) and DAP (60 ± 1 vs. 58 ± 2 mmHg, p = 0.093) were not different between Somali and White participants. In contrast, nocturnal HR was significantly higher in Somalis compared to Whites (72 ± 2 vs. 64 ± 2 beats/minute, p = 0.009). Similarly, SAP (12 ± 2% vs. 12 ± 1%, p = 0.437) and DAP (18 ± 2% vs. 21 ± 2%, p = 0.127) dipping were comparable between groups, while Somali individuals exhibited blunted HR dipping (11 ± 2% vs. 19 ± 2%, p = 0.008) compared to Whites. AASI (0.32 ± 0.03 vs. 0.24 ± 0.03 a.u., p = 0.031) was higher in Somali compared to White individuals. These findings suggest Somali Americans present with impaired nocturnal cardiovascular regulation and increased arterial stiffness, which may place this racial minority at increased cardiovascular risk. Future work to investigate the mechanistic relationships of cardiovascular dysfunction in Somali Americans is warranted. Research grant from Sleep Number to Mayo Clinic for studies of sleep and cardiovascular risk in Somali Americans, and by NIH R01-HL160619, T32-DK007013, T32-HL007111, and T32-HL105355. This is the full abstract presented at the American Physiology Summit 2023 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.

Hypertension is commonly observed with obstructive sleep apnea (OSA), partly due to dysregulation of sympathetic activity. As OSA is considered male-dominant, potential sex differences in the sympathetic regulation of BP have yet to be explored. Hemodynamic responses to an orthostatic challenge have implications for cardiovascular risk and are sympathetically-modulated. Therefore, we tested the hypothesis that females with OSA have differential BP and HR responses to orthostasis relative to males with OSA. 160 individuals not taking antihypertensive medications completed an overnight polysomnography to identify OSA (apnea-hypopnea index ≥5 events/hr). Orthostatic responses were quantified as the changes (Δ) in BP and HR (assessed via brachial cuff) from rest (10min supine) to 60sec post-standing. Females with (n=17, 42±14yrs, 30.7±6.0kg/m2) and without (n=43, 39±12yrs, 27.6±5.7kg/m2) OSA were compared to males with (n=60, 45±11yrs, 31.4±3.8kg/m2) and without (n=40, 39±13yrs, 27.4±3.1kg/m2) OSA using a one-way ANOVA. There were no between-group differences in age (p>0.05 for post-hoc comparisons) and BMI was lower in both females, and males, without OSA relative to males with OSA (p<0.05 for both). ΔSBP did not differ between females with (1±8mmHg) and without (2±8mmHg) OSA nor between males with (4±8mmHg) and without OSA (5±12mmHg, ANOVA p=0.37). Females with OSA had a blunted ΔDBP relative to females without OSA (5±7 vs. 10±6mmHg, p<0.05), whereas males with and without OSA demonstrated similar responses (9±8 vs. 10±6mmHg, p=0.95). ΔHR did not differ between females with (8±8beats/min) and without OSA (9±11beats/min) nor between males with (13±10beats/min) and without OSA (12±10beats/min, ANOVA p=0.06). ΔDBP was not associated with the apnea-hypopnea index (Spearman's r=-0.19, p=0.47; Spearman’s r=0.23, p=0.08) nor nadir SpO2 (Spearman's r=0.27, p=0.29; Spearman’s r=0.06, p=0.64) in females or males with OSA. These data suggest that OSA influences the DBP response to orthostasis in females to a greater extent than males. As DBP is associated with sympathetic activation, this finding could indicate greater sympathetic dysregulation in females, relative to males, with OSA. This work was supported by the National Institutes of Health T32-HL007111 (JMB), HL134808 (NC), HL065176 (PS and VKS), and HL134885 (VKS). This is the full abstract presented at the American Physiology Summit 2023 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.

In America, Black adults are 30% more likely to die from cardiovascular disease (CVD) compared to White adults, and more than half of this racial disparity in CVD‐related mortality may be attributed to the substantially greater prevalence of high blood pressure (BP) in Black adults. Furthermore, compared to White adults with hypertension, Black adults with hypertension are less likely to exhibit a nocturnal reduction in BP (i.e., “dipping”). Importantly, non‐dipping BP is associated with target organ damage and increased CVD risk. However, it is unclear whether young and apparently healthy Black adults exhibit reduced BP dipping compared to their White peers. PURPOSE Therefore, the purpose of this preliminary investigation was to determine whether there are racial differences in BP dipping using ambulatory BP monitoring (ABPM), including 24‐hour‐, daytime‐, and nighttime‐BP, in young and apparently healthy Black and White adults. METHODS We obtained clinical BP and 24‐hour ABPM readings in 10 self‐identified White adults (5M/5F; age: 21.6±4.4 yrs; BMI: 23.8±2.9 kg/m 2 ; Mean±SD) and 7 self‐identified Black adults (3M/4F; age: 21.7±3.5 yrs; BMI: 25.1±2.8 kg/m 2 ). The ABPM monitors were programmed to record BP every 20 and 30 minutes during each participants daytime‐ and nighttime‐period, respectively. True daytime‐ and nighttime‐BP periods were adjusted during analysis based upon participant activity logs. We defined “non‐dipping” as a failure to achieve a dipping ratio of <0.90 (night‐to‐day BP ratio). BP data were compared using independent t‐tests and the Fisher’s exact test was used to compare dipping frequency between races (α=0.05). RESULTS Clinically measured BP (systolic/diastolic) was not different (P>0.05) between White (117±9/67±6 mmHg) and Black (124±12/70±9 mmHg) adults. There was also no difference (P>0.05) in 24‐hour‐BP between White (117±11/66±7 mmHg) and Black (114±14/63±7 mmHg) adults. Likewise, daytime‐BP was not different (P>0.05) between White (122±12/71±8 mmHg) and Black (116±14/66±8 mmHg) participants, nor was there a difference in nighttime‐BP (P>0.05) between White (102±9/51±4 mmHg) and Black (105±13/54±7 mmHg) adults. However, systolic BP dipping was attenuated (P=0.04) in Black (0.90±0.05) compared to White (0.84±0.07) adults. Non‐dipping of systolic BP was observed in 5 of 7 Black participants and 2 of 10 White participants (P=0.06). Diastolic BP dipping in Black adults was 0.79±0.06 and White adults was 0.73±0.09 (P=0.05). Non‐dipping of diastolic BP was observed in 1 of 7 Black participants and 1 of 10 White participants (P=1.00). CONCLUSIONS These preliminary data suggest that despite similar clinical and 24‐hour ambulatory BP compared to White adults, young and apparently healthy Black adults exhibit impaired BP dipping, which may contribute to increased likelihood of CVD.

Insufficiency or irregularity in sleep is associated with high blood pressure (BP) and aortic stiffness, both of which are independent predictors of all‐cause and cardiovascular mortality. The cardiovascular ramifications of short and irregular sleep are well documented in shift workers, but the health implications of possible differences between sleep duration on workdays (WD) and free days (FD) in non‐shift workers is less clear. PURPOSE We sought to examine associations between WD and FD sleep duration, and then to inspect for relationships between WD and FD sleep duration, as well as the difference between WD and FD sleep duration (i.e., sleep irregularity), with BP and indices of arterial stiffness in apparently healthy young adults. We hypothesized 1) participants would sleep less on WD than FD, and 2) that participants with short WD sleep duration would exhibit higher BP and arterial stiffness, and 3) those with greater sleep irregularity would exhibit higher BP and arterial stiffness. METHODS 16 apparently healthy young adults (21.8±4.0 yrs; 24.4±2.9 kg/m 2 ; Mean±SD) participated in this study. All participants completed the Munich ChronoType Questionnaire to assess self‐described WD and FD sleep‐wake behavior. WD and FD sleep duration were determined, and sleep irregularity was quantified as the absolute value of the difference between WD and FD sleep duration. Following 10‐min of supine rest, we used an automated oscillometric device (SphygmoCor XCEL) to measure BP and augmentation index (AIx), an indirect measure of arterial stiffness. Aortic stiffness was then assessed using carotid‐femoral pulse wave velocity (cf‐PWV). WD and FD sleep duration were compared using a paired t‐test and associations between sleep with BP and indices of arterial stiffness were assessed using Pearson correlations, or the non‐parametric equivalent for sleep irregularity. RESULTS WD sleep duration was 492±85 min, FD sleep duration was 480±83 min, and sleep irregularity was 53±49 min. Systolic BP was 120±10 mmHg, diastolic BP was 68±7 mmHg, AIx was 10.9±9.8 %, and cf‐PWV was 5.8±0.7 m/s. WD sleep duration was significantly greater (P<0.01) than FD sleep duration, and WD sleep duration was not associated (P>0.05) with systolic BP (r=0.10), diastolic BP (r=0.10), AIx (r=0.07), or cf‐PWV (r=‐0.18). FD sleep duration was inversely correlated with cf‐PWV (r=‐0.65; P=0.01), but was not associated (P>0.05) with systolic BP (r=‐0.12), diastolic BP (r =‐0.08), or AIx (r=0.25). Sleep irregularity was not associated (P>0.05) with systolic BP (r=0.37), diastolic BP (r=0.45), AIx (r=0.08), or cf‐PWV (r=0.14). CONCLUSIONS Contrary to our hypothesis, FD, but not WD, sleep duration was associated with aortic stiffness in apparently healthy young adults. Average sleep duration of our cohort exceeded the recommended minimum of 7 hours per night and sleep irregularity was small (i.e., <60 min on average), thus potentially masking elevations in BP and arterial stiffness seen with short and/or irregular sleep such as in shift workers.

Stimuli that evoke pain stimulate the sympathetic nervous system leading to downstream vascular and hemodynamic adjustments. In clinical populations and older individuals, the perception of pain is associated with cardiovascular responses (e.g., heart rate, blood pressure, and arterial stiffness). However, there are extensive inter‐individual differences in the perception of pain, pain perception may be influenced by age, and it’s unclear if pain is associated with cardiovascular responses in younger adults. PURPOSE Therefore, we sought to determine whether heart rate, blood pressure, and arterial stiffness responses to sympathoexcitatory stimuli were associated with perceived pain, in apparently healthy young adults METHODS 17 young adults (21.6±3.9 yrs; BMI: 24.4±2.8 kg/m 2 ;Mean±SD) participated in this investigation. Following 10‐min of supine rest, we measured heart rate (HR) and mean arterial pressure (MAP), via pulse wave analysis (PWA), and arterial stiffness via carotid‐femoral pulse wave velocity (cf‐PWV). Measures were obtained in duplicate then averaged for analysis. Participants then performed a 3‐min isometric handgrip exercise (HG) at 30% of maximum voluntary contraction, which was immediately followed by 3‐min of brachial cuff‐occlusion at 240mmHg. Perceived pain was assessed via visual analog scale (0‐10; 0=no pain, 10=most pain) at the first minute of each stimulus. HR and MAP were assessed at minute two and arterial stiffness was acquired in the final minute of each stimulus. Associations between perceived pain scores during HG and cuff‐occlusion with percent change in cardiovascular responses were assessed using Spearman’s correlations (α=0.05) RESULTS During HG, significant (P<0.01) increases in HR (pre: 63±6 vs. post: 78±11 bpm; 23±15 %), MAP (pre: 86±9 vs. post: 105±14 mmHg; 22±10 %), and cf‐PWV (pre: 6.5±1.7 vs. post: 7.2±1.0 m/s; 13±26 %) were observed. During cuff‐occlusion, relative to pre, significant (P<0.05) increases in MAP (post: 100±13 mmHg; 18±15%) and cf‐PWV (post: 7.2±1.4 m/s; 14±13%), but not (P>0.05) HR (post: 64±7 bpm; 7±6%) were observed. Perceived pain during cuff‐occlusion (3.73±1.79 A.U.) was significantly greater (P=0.01) than during HG (1.88±1.20 A.U.). While no relationships were observed between perceived pain and cardiovascular responsiveness during HG (P>0.05) with HR (r=0.28; P=0.28), BP (r=0.45; P=0.07), or cf‐PVW (r=0.28; P=0.28), perceived pain was associated with increases in BP (r=0.57; P=0.02) and cf‐PWV (r=0.55; P=0.02;), but not HR (r=0.19; P=0.47), during cuff‐occlusion. CONCLUSIONS While pain during HG was not associated with cardiovascular responses, significantly greater cuff‐occlusion evoked pain was associated with cardiovascular responsiveness. Our data suggests that the relation between perceived pain and cardiovascular responsiveness to sympathoexcitatory stimuli exists in younger adults, although additional data in larger cohorts and using varied stimuli are warranted.