Nocturnal Hemodynamics in Somali Americans: Implications for Cardiovascular Risk.

INTRODUCTION: Cardiovascular health disparities are present within several minority communities, but it is unclear if such disparities are present in a growing African American subpopulation, Somali Americans, who differ genetically and culturally from African Americans of Western African ancestry. Ambulatory blood pressure (BP) monitoring remains a gold standard measure to examine 24-h BP patterns to stratify cardiovascular risk profile. We sought to examine differences in the 24-h BP profile in a sample of young Somali Americans and compare their BP patterns to White study participants. We hypothesized that their BP and heart rate (HR) would be higher compared to closely matched White participants. METHODS: We recruited 50 participants (25 Somali) in whom BP recordings were obtained every 20 min throughout the entire 24-h monitoring period to quantify BP, HR, and ambulatory arterial stiffness. Daytime BP/HR was quantified between 10:00 a.m. and 8:00 p.m., and nighttime BP/HR was assessed between 12:00 a.m. and 6:00 a.m. RESULTS: Daytime BP and HR were similar between racial groups (p > 0.05). Nighttime BP was similar between groups (p > 0.05), but Somali American individuals exhibited a higher nocturnal HR compared to White participants (p = 0.013). Nocturnal dipping in diastolic BP and HR dipping was attenuated in Somali Americans compared to White adults (p = 0.038, 0.007). Somali participants also had higher ambulatory arterial stiffness (p = 0.045). CONCLUSION: Twenty four-hour hemodynamics, specifically ambulatory arterial stiffness, nocturnal BP, and nocturnal HR, differ in young Somali Americans compared to White adults. These findings provide new insight into potential cardiovascular health disparities and future cardiovascular risk within the burgeoning Somali American community.

Sex Differences in Neurovascular Control: Implications for Obstructive Sleep Apnea.

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.

Combined inorganic nitrate/nitrite supplementation blunts α-mediated vasoconstriction during exercise in patients with type 2 diabetes.

AIMS: Patients with type 2 diabetes mellitus (T2DM) have reduced vasodilatory responses during exercise partially attributable to low nitric oxide (NO) levels. Low NO contributes to greater α-adrenergic mediated vasoconstriction in contracting skeletal muscle. We hypothesized boosting NO bioavailability via 8wks of active beetroot juice (BRA, 4.03 mmol nitrate, 0.29 mmol nitrite, n = 19) improves hyperemia, via reduced α-mediated vasoconstriction, during handgrip exercise relative to nitrate/nitrite-depleted beetroot juice (BRP, n = 18) in patients with T2DM. METHODS: Forearm blood flow (FBF) and vascular conductance (FVC) were calculated at rest and during handgrip exercise (20%max, 20contractions·min-1). Phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were infused intra-arterially during independent trials to determine the influence of α-mediated vasoconstriction on exercise hyperemia. Vasoconstriction was quantified as the percent-reduction in FVC during α-agonist infusion, relative to pre-infusion, as well as the absolute change in %FVC during exercise relative to the respective rest trial (magnitude of sympatholysis). RESULTS: ΔFBF (156 ± 69 to 175 ± 73 ml min-1) and ΔFVC (130 ± 54 to 156 ± 63 ml min-1·100 mmHg-1, both P < 0.05) during exercise were augmented following BRA, but not BRP (P = 0.96 and 0.51). Phenylephrine-induced vasoconstriction during exercise was blunted following BRA (-17.1 ± 5.9 to -12.6 ± 3.1%, P < 0.01), but not BRP (P = 0.58) supplementation; the magnitude of sympatholysis was unchanged by either (beverage-by-time P = 0.15). BRA supplementation reduced dexmedetomidine-induced vasoconstriction during exercise (-23.3 ± 6.7 to -19.7 ± 5.2%) and improved the corresponding magnitude of sympatholysis (25.3 ± 11.4 to 34.4 ± 15.5%, both P < 0.05). CONCLUSIONS: BRA supplementation improves the hyperemic and vasodilatory responses to exercise in patients with T2DM which appears to be attributable to reduced α-adrenergic mediated vasoconstriction in contracting skeletal muscle.

Sodium nitrate supplementation improves blood pressure reactivity in patients with peripheral artery disease.

BACKGROUND & AIMS: Peripheral artery disease (PAD) is characterized by elevated blood pressure (BP), low nitric oxide availability (NO), and exaggerated pressor responses to sympatho-excitatory stressors. Inorganic nitrate reduces peripheral BP in healthy and chronically diseased populations. The objective of this study was to investigate the effects of eight-weeks of sodium nitrate (NaNO3) supplementation on indices of BP in PAD patients. METHODS: 21 patients with PAD were recruited to participate in this study, undergoing 8-weeks of NaNO3 (n = 13; 73 ± 9 years) or placebo (n = 8; 69 ± 10 years) supplementation. BP responsiveness to a cold pressor test (CPT) were examined prior to and following the supplementation period. The systolic BP response (change from rest) during the first (26 ± 10 vs. 19 ± 11 mmHg) and second minutes (32 ± 10 vs. 26 ± 12 mmHg) of CPT were reduced following NaNO3 (P < 0.05 for both) but not after placebo (first minute: 22 ± 10 vs. 24 ± 10 mmHg, P = 0.30; second minute 26 ± 10 vs 27 ± 10 mmHg, P = 0.72) supplementation. CONCLUSION: Our data suggest that eight-weeks of NaNO3 supplementation reduces BP responsiveness to sympatho-excitatory stimuli. CLINICAL TRIALS REGISTRATION NUMBER: NCT01983826.

A consensus method for estimating physical activity levels in adults using accelerometry.

Identifying the best analytical approach for capturing moderate-to-vigorous physical activity (MVPA) using accelerometry is complex but inconsistent approaches employed in research and surveillance limits comparability. We illustrate the use of a consensus method that pools estimates from multiple approaches for characterising MVPA using accelerometry. Participants (n = 30) wore an accelerometer on their right hip during two laboratory visits. Ten individual classification methods estimated minutes of MVPA, including cut-point, two-regression, and machine learning approaches, using open-source count and raw inputs and several epoch lengths. Results were averaged to derive the consensus estimate. Mean MVPA ranged from 33.9-50.4 min across individual methods, but only one (38.9 min) was statistically equivalent to the criterion of direct observation (38.2 min). The consensus estimate (39.2 min) was equivalent to the criterion (even after removal of the one individual method that was equivalent to the criterion), had a smaller mean absolute error (4.2 min) compared to individual methods (4.9-12.3 min), and enabled the estimation of participant-level variance (mean standard deviation: 7.7 min). The consensus method allows for addition/removal of methods depending on data availability or field progression and may improve accuracy and comparability of device-based MVPA estimates while limiting variability due to convergence between estimates.

Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults.

Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may, therefore, improve age-associated changes in shear rate as well as exercise hyperemia. Ten older adults (age: 67 ± 3 yr) consumed 4.03 mmol nitrate and 0.29 mmol nitrite (active) or devoid of both (placebo) daily for 4 wk in a randomized, double-blinded, crossover fashion. Brachial artery diameter (D) and blood velocity (Vmean) were measured via Doppler ultrasound at rest for the characterization of shear profile as well as during two handgrip exercise trials (4 and 8 kg) for calculation of forearm blood flow (Vmean × cross-sectional area, FBF) and conductance [FBF/mean arterial pressure, forearm vascular conductance (FVC)]. Plasma [nitrate] and [nitrite] increased following active (P < 0.05 for both) but not placebo (P = 0.68 and 0.40, respectively) supplementation. Neither mean nor antegrade shear rate changed following either supplement (beverage-by-time P = 0.14 and 0.21, respectively). Retrograde (-13.4 ± 7.0 to -9.7 ± 6.8·s-1) and oscillatory (0.20 ± 0.08 to 0.15 ± 0.09 A.U., P < 0.05 for both) shear decreased following active, but not placebo (P = 0.81 and 0.70, respectively), supplementation. The FBF response (Δ from rest) to neither 4-kg nor 8-kg trials changed following either supplement (beverage-by-time P = 0.53 and 0.11, respectively). Similarly, no changes were observed in FVC responses to 4-kg or 8-kg trials (beverage-by-time P = 0.23 and 0.07, respectively). These data indicate that inorganic nitrate supplementation improves conduit artery shear profiles, but not exercise hyperemia, in older adults.NEW & NOTEWORTHY We report for the first time, to our knowledge, that 4 wk of inorganic nitrate supplementation attenuates retrograde and oscillatory shear in the brachial artery of older adults. However, this was not associated with greater hyperemic or vasodilatory responses to exercise. In sum, these data highlight favorable changes in shear patterns with aging, which may reduce the risk of atherosclerotic cardiovascular disease.

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

Effect of Age and Acute Exercise on Circulating Angioregulatory Factors.

The balance of angiogenic factors, including vascular endothelial growth factor (VEGF), and angiostatic factors, like thrombospondin-1 (TSP-1) and endostatin, controls striated muscle angiogenic responses to exercise training. The effect of age on circulating levels of these factors following a bout of exercise is unclear. The authors hypothesized that older adults would have lower circulating VEGF but higher TSP-1 and endostatin after exercise compared with young adults. Ten young and nine older participants cycled for 45 min at 60% estimated HRmax. Serum [VEGF], [TSP-1], and [endostatin] obtained before (PREX), immediately after (POSTX0), and 3 hr after (POSTX3) exercise were analyzed. [VEGF] increased in older adults only from PREX to POSTX0 (p < .05). [TSP-1] increased in both age groups (p < .05). There was no effect of age or exercise on [endostatin]. In conclusion, immediately after exercise, both groups had a similar increase in [TSP-1], but [VEGF] increased in older adults only.

Greater α1-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes.

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (n = 30) as well as nondiabetic controls (n = 15) with similar age (59 ± 9 vs. 60 ± 9 yr, P = 0.69) and body mass index (31.4 ± 5.2 vs. 29.5 ± 4.6 kg/m2, P = 0.48). Intra-arterial infusion of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were used to induce vasoconstriction: [(FVCwith drug - FVCpredrug)/FVCpredrug × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min-1·100 mmHg-1, P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α1- (-16.9 ± 5.9 vs. -11.3 ± 3.8%) and α2-mediated vasoconstriction (-23.5 ± 7.1 vs. -19.0 ± 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 ± 12.2 vs. 23.1 ± 8.1%, P < 0.05) whereas groups were similar during DEX trials (24.6 ± 12.3 vs. 27.6 ± 13.4%, P = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater α1-mediated vasoconstriction in contracting skeletal muscle.NEW & NOTEWORTHY Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α1-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.

Aerobic exercise offsets endothelial dysfunction induced by repetitive consumption of sugar-sweetened beverages in young healthy men.

Consumption of a single, sugar-sweetened beverage (SSB) impairs vascular endothelial function. Regular aerobic exercise improves endothelium-dependent vasodilation; however, it is unknown whether these beneficial effects persist with frequent SSB consumption. Therefore, the purpose of this study was twofold; we studied the effects of repetitive SSB consumption (75 g d-glucose, 3 times/day) for 1 wk (Glu, n = 13, 23 ± 4 yr, 23.5 ± 3.4 kg/m2) on endothelium-dependent vasodilation (FMD). Then, in a separate cohort, we investigated whether 45 min of moderate-intensity aerobic exercise on five separate days offset the hypothesized decrease in FMD during the Glu protocol (Glu+Ex, n = 11, 21 ± 3 yr, 23.8 ± 2.4 kg/m2). Baseline, fasting [glucose] (P = 0.15), [insulin] (P = 0.25), %FMD (P = 0.48), absolute FMD (P = 0.66), and shear rate area under the curve (SRAUC; P = 0.82) were similar between groups. Following the interventions, fasting [glucose] (Glu: 94 ± 6 to 92 ± 6 mg/dL, Glu+Ex: 89 ± 8 to 87 ± 6 mg/dL, P = 0.74) and [insulin] (Glu: 11.3 ± 6.2 to 11.8 ± 8.9 µU/mL, Glu+Ex: 8.7 ± 2.9 to 9.4 ± 3.2 µU/mL, P = 0.89) were unchanged. %FMD was reduced in Glu (6.1 ± 2.2 to 5.1 ± 1.3%) and increased in Glu+Ex (6.6 ± 2.2 to 7.8 ± 2.4%, P < 0.05 for both). SRAUC increased similarly in both Glu [17,715 ± 8,275 to 22,922 ± 4,808 arbitrary units (A.U.)] and Glu+Ex (18,216 ± 4,516 to 21,666 ± 5,392 A.U., main effect of time P < 0.05). When %FMD was adjusted for SRAUC, attenuation was observed in Glu (0.41 ± 0.18 to 0.23 ± 0.08%/s × 103, P < 0.05) but not Glu+Ex (0.38 ± 0.14 to 0.38 ± 0.13%/s × 103, P = 0.88). Despite unchanged fasting [glucose] and [insulin], repeated consumption of SSBs impaired conduit artery vascular endothelial function. Additionally, subjects who engaged in regular moderate-intensity aerobic exercise did not demonstrate the same SSB-induced endothelial dysfunction. Collectively, these data suggest aerobic exercise may offset the deleterious effects of repetitive SSB consumption.

Dietary nitrate does not acutely enhance skeletal muscle blood flow and vasodilation in the lower limbs of older adults during single-limb exercise.

PURPOSE: Blood flow (BF) and vasodilator responses to knee-extension exercise are attenuated in older adults across an exercise transient (onset, kinetics, and steady-state), and reduced nitric oxide bioavailability (NO) has been hypothesized to be a primary mechanism contributing to this attenuation. We tested the hypothesis acute dietary nitrate (NO3-) supplementation (~ 4.03 mmol NO3- and 0.29 mmol NO2-) would improve leg vasodilator responses across an exercise transient during lower limb exercise in older adults. METHODS: Older (n = 10) untrained adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRmax) prior to and 2-h after consuming a NO3- or placebo beverage in a double-blind, randomized fashion. Femoral artery BF was measured by Doppler ultrasound. Vascular conductance was calculated using BF and mean arterial pressure. RESULTS: Acute ingestion of dietary NO3- enhanced plasma [NO3-] and [NO2-] (P < 0.05). Neither dietary NO3- or placebo enhanced vasodilator responses at the onset of exercise or during steady state at 20% and 40% WRmax (P > 0.05). Leg vasodilator kinetics during rhythmic exercise remained unchanged following NO3- and placebo ingestion (P > 0.05). CONCLUSIONS: The key findings of this study are that despite increasing plasma [NO3-] and [NO2-], acute dietary NO3- intake had no effect on (1) rapid hyperaemic or vasodilator responses at the onset of exercise; (2) hyperaemic and vasodilator responses during steady-state submaximal exercise; or (3) kinetics of vasodilation preceding steady-state responses. Collectively, these findings suggest that low dose dietary NO3- supplementation does not improve hyperaemic and vasodilator responses across an exercise transient in older adults.

Development of cut-points for determining activity intensity from a wrist-worn ActiGraph accelerometer in free-living adults.

Despite recent popularity of wrist-worn accelerometers for assessing free-living physical behaviours, there is a lack of user-friendly methods to characterize physical activity from a wrist-worn ActiGraph accelerometer. Participants in this study completed a laboratory protocol and/or 3-8 hours of directly observed free-living (criterion measure of activity intensity) while wearing ActiGraph GT9X Link accelerometers on the right hip and non-dominant wrist. All laboratory data (n = 36) and 11 participants' free-living data were used to develop vector magnitude count cut-points (counts/min) for activity intensity for the wrist-worn accelerometer, and 12 participants' free-living data were used to cross-validate cut-point accuracy. The cut-points were: <2,860 counts/min (sedentary); 2,860-3,940 counts/min (light); and ≥3,941counts/min (moderate-to-vigorous (MVPA)). These cut-points had an accuracy of 70.8% for assessing free-living activity intensity, whereas Sasaki/Freedson cut-points for the hip accelerometer had an accuracy of 77.1%, and Hildebrand Euclidean Norm Minus One (ENMO) cut-points for the wrist accelerometer had an accuracy of 75.2%. While accuracy was higher for a hip-worn accelerometer and for ENMO wrist cut-points, the high wear compliance of wrist accelerometers shown in past work and the ease of use of count-based analysis methods may justify use of these developed cut-points until more accurate, equally usable methods can be developed.

Impaired modulation of postjunctional α1 - but not α2 -adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women.

KEY POINTS: Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α1 - and α2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α1 - (via intra-arterial infusion of phenylephrine) but not α2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. ABSTRACT: Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α1 -agonist) or dexmedetomidine (α2 -agonist) was administered during the last 3 min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic agonist infusions from baseline (resting trial) or from steady-state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α1 - and α2 -agonist stimulation was similar between YW and PMW. During exercise, α1 -mediated vasoconstriction was blunted in YW vs. PMW at relative (-6 ± 2% vs. -15 ± 3%) and absolute (-4 ± 2% vs. -14 ± 5%) workloads, such that blood flow and FVC were lower in PMW (P < 0.05 for all). Conversely, α2 -mediated vasoconstriction was similar between YW and PMW at relative (-22 ± 3% vs. -22 ± 4%; P > 0.05) and absolute (-19 ± 3% vs. -18 ± 4%; P > 0.05) workloads. Collectively, these findings demonstrate that despite similar α-adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α1 -adrenergic vasoconstriction in contracting skeletal muscle.

Hypercapnia-induced shear-mediated dilation in the internal carotid artery is blunted in healthy older adults.

This study aimed to elucidate the effect of aging on shear-mediated dilation of the common and internal carotid arteries (CCA and ICA, respectively). Hypercapnia-induced shear-mediated dilation in the CCA and ICA were assessed in 10 young (5 women and 5 men, 23 ± 1 yr) and 10 older (6 women/4 men, 68 ± 1 yr) healthy adults. Shear-mediated dilation was induced by two levels of hypercapnia (target end-tidal Pco2, +5 and +10 mmHg from individual baseline values) and was calculated as the percent rise in peak diameter from baseline diameter. There were no differences in shear-mediated dilation between young and older adults in either artery under lower levels of hypercapnia (CCA: 2.8 ± 0.6 vs. 2.0 ± 0.3%, P = 0.35; ICA: 4.6 ± 0.8 vs 3.6 ± 0.4%, P = 0.37). However, shear-mediated dilation in response to higher levels of hypercapnia was attenuated in older compared with young adults in the ICA (4.5 ± 0.5 vs. 7.9 ± 1.2%, P < 0.01) but not in the CCA (3.7 ± 0.6 vs. 4.5 ± 0.8%, P = 0.35). Shear-mediated dilation was significantly correlated to the percent change in shear rate in the ICA (young: r = 0.55, P = 0.01; older: r = 0.49, P = 0.03) but not in the CCA in either young or older adults (young: r = -0.30, P = 0.90; older: r = 0.16, P = 0.50). These data indicate that aging attenuates shear-mediated dilation of the ICA in response to higher levels of hypercapnia, and shear rate is an important stimulus for hypercapnic vasodilation of the ICA in both young and older adults. The present results may provide insights into age-related changes in the regulation of cerebral circulation in healthy adults. NEW & NOTEWORTHY We explored the effect of aging on shear-mediated dilation in the common and internal carotid arteries (CCA and ICA, respectively) in healthy adults. Our findings suggest that 1) aging attenuates shear-mediated dilation of the ICA but not the CCA and 2) shear rate is an important stimulus for hypercapnic vasodilation of the ICA in young and older adults. These findings may provide insights into the age-related changes in cerebrovascular regulation of healthy adults.

Inorganic nitrate supplementation attenuates peripheral chemoreflex sensitivity but does not improve cardiovagal baroreflex sensitivity in older adults.

Aging is associated with increased peripheral chemoreceptor activity, reduced nitric oxide (NO) bioavailability, and attenuation of cardiovagal baroreflex sensitivity (BRS), collectively increasing the risk of cardiovascular disease. Evidence suggests that NO may attenuate peripheral chemoreflex sensitivity and increase BRS. Exogenous inorganic nitrate ([Formula: see text]) increases NO bioavailability via the [Formula: see text]-[Formula: see text]-NO pathway. Our hypothesis was that inorganic [Formula: see text] supplementation would attenuate peripheral chemoreflex sensitivity and enhance spontaneous cardiovagal BRS in older adults. We used a randomized, placebo-controlled crossover design in which 13 older (67 ± 3 yr old) adults ingested beetroot powder containing (BRA) or devoid of (BRP) [Formula: see text] and [Formula: see text] daily over 4 wk. Spontaneous cardiovagal BRS was assessed over 15 min of rest and was quantified using the sequence method. Chemoreflex sensitivity was assessed via ~5 min of hypoxia (10% fraction of inspired O2) and reported as the slope of the relationship between O2 saturation (%[Formula: see text]) and minute ventilation (in l/min) or heart rate (in beats/min). Ventilatory responsiveness to hypoxia was reduced after BRA (from -0.14 ± 0.04 to -0.05 ± 0.02 l·min-1·%[Formula: see text]-1, P = 0.01) versus BRP (from -0.10 ± 0.05 to -0.11 ± 0.05 l·min-1·%[Formula: see text]-1, P = 0.80), with no differences in heart rate responsiveness (BRA: from -0.47 ± 0.06 to -0.33 ± 0.04 beats·min-1·%[Formula: see text]-1, BRP: from -0.48 ± 0.07 to -0.42 ± 0.06 beats·min-1·%[Formula: see text]-1) between conditions (interaction effect, P = 0.41). Spontaneous cardiovagal BRS was unchanged after BRA and BRP (interaction effects, P = 0.69, 0.94, and 0.39 for all, up, and down sequences, respectively), despite a reduction in resting systolic and mean arterial blood pressure in the experimental (BRA) group ( P < 0.01 for both). These findings illustrate that inorganic [Formula: see text] supplementation attenuates peripheral chemoreflex sensitivity without concomitant change in spontaneous cardiovagal BRS in older adults. NEW & NOTEWORTHY Exogenous inorganic nitrate supplementation attenuates ventilatory, but not heart rate, responsiveness to abbreviated hypoxic exposure in older adults. Additionally, inorganic nitrate reduces systolic and mean arterial blood pressure without affecting spontaneous cardiovagal baroreflex sensitivity. These findings suggest that inorganic nitrate may attenuate sympathetically oriented pathologies associated with aging.

Reduced blood pressure responsiveness to skeletal muscle metaboreflex activation in older adults following inorganic nitrate supplementation.

The vasoactive molecule nitric oxide (NO) contributes to regulation of blood pressure (BP) at rest and during exercise. Age-related exaggerated increased BP responses during exercise have been proposed to be due in part to a decreased NO bioavailability and possibly an enhanced skeletal muscle metaboreflex. In the present study we sought to determine if age-related differences in BP responses to skeletal muscle metaboreflex activation exist. Additionally, since NO bioavailability can be improved with exogenous nitrate (NO3-) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO3- supplementation would reduce BP responses to muscle metaboreflex activation in healthy older adults. 13 older adults (67 ±â€¯1 years) participated in a randomized, double-blind, placebo controlled crossover study consisting of four weeks of NO3- supplementation [beetroot powder; 250 mg (∼4.03 mmol) of NO3- and 20 mg (∼0.29 mmol) of NO2-] and four weeks of placebo (beetroot powder devoid of NO3-/NO2-). Skeletal muscle metaboreflex testing consisted of isometric handgrip exercise (IHG) at 30% of maximal voluntary contraction immediately followed by post exercise forearm ischemia (PEI), which was achieved by inflation of a rapid pressure cuff (240 mmHg) around the upper arm. BP responses were analyzed as the change (Δ) from baseline to the end of IHG and PEI. An additional 10 young adults (25 ±â€¯1 years) were recruited to serve as a reference cohort and address if BP responses to skeletal muscle metaboreflex activation were greater with aging. BP responses to IHG were similar between the young and older adults. However, older adults demonstrated a greater increase in systolic BP during PEI (P < 0.05). Plasma NO3- and NO2-were increased following NO3- supplementation in older adults (P < 0.01). ΔSystolic BP (19 ±â€¯2 vs. 13±3 mmHg, P < 0.05), ΔDiastolic BP (7 ±â€¯1 vs. 5±1 mmHg, P < 0.05) and ΔMean arterial pressure (11 ±â€¯1 vs. 8±2 mmHg, P < 0.05) were reduced during PEI following four weeks of NO3-supplementation, whereas placebo had no effect on ΔSystolic BP (16 ±â€¯2 vs. 17±2 mmHg), ΔDiastolic BP (5 ±â€¯1 vs. 7±1 mmHg), and ΔMean arterial pressure (8 ±â€¯1 vs. 10±1 mmHg) during PEI (all P > 0.05). These data suggest that inorganic NO3- supplementation attenuates skeletal muscle metaboreflex mediated increases in BP during exercise in older adults.

Inorganic nitrate supplementation enhances functional capacity and lower-limb microvascular reactivity in patients with peripheral artery disease.

Peripheral artery disease (PAD) is characterized by functional and vascular impairments as well as elevated levels of inflammation which are associated with reduced nitric oxide (NO) bioavailability. Inorganic nitrate supplementation boosts NO bioavailability potentially improving functional and vasodilatory capacities and may reduce inflammation. Twenty-one patients with PAD were randomly assigned to sodium nitrate (NaNO3) or placebo supplementation groups for eight-weeks. Outcome measures included a 6-min walk test (6 MWT), blood flow and vasodilator function in the forearm and calf, as well as plasma inflammatory and adhesion biomarker concentrations. NaNO3 elevated plasma nitrate (32.3 ±â€¯20.0 to 379.8 ±â€¯204.6 µM) and nitrite (192.2 ±â€¯51.8 to 353.1 ±â€¯134.2 nM), improved 6 MWT performance (387 ±â€¯90 to 425 ±â€¯82 m), peak calf blood flow (BFPeak; 11.6 ±â€¯4.9 to 14.1 ±â€¯5.1 mL/dL tissue/min), and peak calf vascular conductance (VCPeak; 11.1 ±â€¯4.3 to 14.2 ±â€¯4.9 mL/dL tissue/min/mmHg) (p < 0.05 for all). Improvements in calf BFPeak (r = 0.70, p < 0.05) and VCPeak (r = 0.61, p < 0.05) correlated with changes in 6 MWT distance. Placebo supplementation did not change plasma nitrate or nitrite, 6 MWT, calf BFPeak, or calf VCPeak. Forearm vascular function nor inflammatory and adhesion biomarker concentrations changed in either group. Eight-weeks of NaNO3 supplementation improves vasodilatory capacity in the lower-limbs of patients with PAD, which correlated with improvement in functional capacity.

Participation in a Tele-Stroke Program Improves Timeliness of Intravenous Thrombolysis Delivery.

BACKGROUND: We sought to assess the effects of participation in a tele-stroke program on timeliness of intravenous tissue plasminogen activator (IVtPA) administration. METHODS: Among 259 consecutive acute ischemic stroke patients treated with IVtPA through the Rush tele-stroke program, we compared two cohorts: Period 1 (July 2011 to June 2013) and Period 2 (July 2013 to July 2014). We collected data on demographics, National Institutes of Health Stroke Scale (NIHSS), and times of last known normal (LKN), initiation of tele-stroke consult, and IVtPA administration. RESULTS: The mean age was 69.6 years, 56% were female, the mean NIHSS was 11.8, and 41.7% patients were transferred to the hub site. The mean time from initiation of tele-stroke consult to IVtPA administration was 42.2 min. Time from initiation of tele-stroke consult to IVtPA administration improved from Period 1 to Period 2 (49.9 min vs. 35 min, p < 0.0001). This improvement was due to faster mean time from initiation of tele-stroke consult to IVtPA advised (17.4 min vs. 12.5 min, p < 0.0001) and faster mean time from IVtPA advised to administration (33.1 min vs. 22.5 min, p < 0.0001). The mean time from LKN to IVtPA given was also significantly improved (148.6 min vs. 160.9 min, p 0.045). CONCLUSIONS: Participation in a tele-stroke program associated with improvement in the timeliness of IVtPA delivery.

Impact of PAP on the gut microbiome in OSA: A pilot study.

OBJECTIVE/BACKGROUND: Microbes within the gastrointestinal tract have emerged as modulators of the host's health. Obstructive sleep apnea (OSA) is characterized by intermittent partial, or complete, airway closure during sleep and is associated with increased risk of non-communicable diseases as well as dysbiosis of the gut microbiome. Thus, we investigated if improving nocturnal airway patency via positive airway pressure (PAP) therapy improves gut microbial diversity in recently diagnosed patients with moderate-to-severe OSA (apnea-hypopnea index ≥15.0 events/hr). PATIENTS/METHODS: Eight subjects (3 F, 56±9yrs, 33.5 ± 7.7 kg/m2, 45.0 ± 38.4 events/hr) provided stool samples before, and two months after, PAP therapy (mean adherence of 95 ± 6%, residual apnea-hypopnea index of 4.7 ± 4.6 events/hr). RESULTS: While the Shannon diversity index tended to increase following PAP (3.96 ± 0.52 to 4.18 ± 0.56, p = 0.08), there were no changes in the Observed (1,088 ± 237 to 1,136 ± 289, p = 0.28) nor Inverse-Simpson (22.4 ± 12.99 to 26.6 ± 18.23, p = 0.28) alpha diversity indices. There were also no changes in beta diversity assessed using the Bray-Curtis (p = 0.98), Jaccard (p = 0.99), WUniFrac (p = 0.98), GUniFrac (p = 0.98), or UniFrac (p = 0.98) methods. No changes in differential abundance taxa were found using a false discovery rate threshold of <0.20. CONCLUSIONS: Our data are the first to report that PAP therapy may not offset, or reverse, gut dysbiosis in patients with OSA. Accordingly, interventions which improve gut microbial health should be explored as potential adjunctive treatment options in patients with OSA to reduce their risk of developing non-communicable diseases.