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.

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.

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.

Eight weeks of inorganic nitrate/nitrite supplementation improves aerobic exercise capacity and the gas exchange threshold in patients with type 2 diabetes.

Patients with type 2 diabetes mellitus (T2DM) have reduced exercise capacity, indexed by lower maximal oxygen consumption (V̇o2max) and achievement of the gas exchange threshold (GET) at a lower % V̇o2max. The ubiquitous signaling molecule nitric oxide (NO) plays a multifaceted role during exercise and, as patients with T2DM have poor endogenous NO production, we investigated if inorganic nitrate/nitrite supplementation (an exogenous source of NO) improves exercise capacity in patients with T2DM. Thirty-six patients with T2DM (10F, 59 ± 9 yr, 32.0 ± 5.1 kg/m2, HbA1c = 7.4 ± 1.4%) consumed beetroot juice containing either inorganic nitrate/nitrite (4.03 mmol/0.29 mmol) or a placebo (0.8 mmol/0.00 mmol) for 8 wk. A maximal exercise test was completed before and after both interventions. V̇o2max was determined by averaging 15-s data, whereas the GET was identified using the V-slope method and breath-by-breath data. Inorganic nitrate/nitrite increased both absolute (1.96 ± 0.67 to 2.07 ± 0.75 L/min) and relative (20.7 ± 7.0 to 21.9 ± 7.4 mL/kg/min, P < 0.05 for both) V̇o2max, whereas no changes were observed following placebo (1.94 ± 0.40 to 1.90 ± 0.39 L/min, P = 0.33; 20.0 ± 4.2 to 19.7 ± 4.6 mL/kg/min, P = 0.39). Maximal workload was also increased following inorganic nitrate/nitrite supplementation (134 ± 47 to 140 ± 51 W, P < 0.05) but not placebo (138 ± 32 to 138 ± 32 W, P = 0.98). V̇o2 at the GET (1.11 ± 0.27 to 1.27 ± 0.38L/min) and the %V̇o2max in which GET occurred (56 ± 8 to 61 ± 7%, P < 0.05 for both) increased following inorganic nitrate/nitrite supplementation but not placebo (1.10 ± 0.23 to 1.08 ± 0.21 L/min, P = 0.60; 57 ± 9 to 57 ± 8%, P = 0.90) although the workload at GET did not achieve statistical significance (group-by-time P = 0.06). Combined inorganic nitrate/nitrite consumption improves exercise capacity, maximal workload, and promotes a rightward shift in the GET in patients with T2DM. This manuscript reports data from a registered Clinical Trial at ClinicalTrials.gov ID: NCT02804932.NEW & NOTEWORTHY We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.

Effects of Combined Inorganic Nitrate and Nitrite Supplementation on Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 Diabetes: A Pilot Randomized Controlled Trial.

Nitric oxide (NO) stimulates mitochondrial biogenesis in skeletal muscle. However, NO metabolism is disrupted in individuals with type 2 diabetes mellitus (T2DM) potentially contributing to their decreased cardiorespiratory fitness (i.e., VO2max) and skeletal muscle oxidative capacity. We used a randomized, double-blind, placebo-controlled, 8-week trial with beetroot juice containing nitrate (NO3−) and nitrite (NO2−) (250 mg and 20 mg/day) to test potential benefits on VO2max and skeletal muscle oxidative capacity in T2DM. T2DM (N = 36, Age = 59 ± 9 years; BMI = 31.9 ± 5.0 kg/m2) and age- and BMI-matched non-diabetic controls (N = 15, Age = 60 ± 9 years; BMI = 29.5 ± 4.6 kg/m2) were studied. Mitochondrial respiratory capacity was assessed in muscle biopsies from a subgroup of T2DM and controls (N = 19 and N = 10, respectively). At baseline, T2DM had higher plasma NO3− (100%; p < 0.001) and lower plasma NO2− levels (−46.8%; p < 0.0001) than controls. VO2max was lower in T2DM (−26.4%; p < 0.001), as was maximal carbohydrate- and fatty acid-supported oxygen consumption in permeabilized muscle fibers (−26.1% and −25.5%, respectively; p < 0.05). NO3−/NO2− supplementation increased VO2max (5.3%; p < 0.01). Further, circulating NO2−, but not NO3−, positively correlated with VO2max after supplementation (R2= 0.40; p < 0.05). Within the NO3−/NO2− group, 42% of subjects presented improvements in both carbohydrate- and fatty acid-supported oxygen consumption in skeletal muscle (vs. 0% in placebo; p < 0.05). VO2max improvements in these individuals tended to be larger than in the rest of the NO3−/NO2− group (1.21 ± 0.51 mL/(kg*min) vs. 0.31 ± 0.10 mL/(kg*min); p = 0.09). NO3−/NO2− supplementation increases VO2max in T2DM individuals and improvements in skeletal muscle oxidative capacity appear to occur in those with more pronounced increases in VO2max.

Dietary Inorganic Nitrate/Nitrite Supplementation Reduces Central and Peripheral Blood Pressure in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have increased cardiovascular risk due to elevated blood pressure (BP). As low levels of nitric oxide (NO) may contribute to increased BP, we determined if increasing NO bioavailability via eight weeks of supplementation with beetroot juice containing inorganic nitrate/nitrite (4.03 mmol nitrate, 0.29 mmol nitrite) improves peripheral and central BP relative to nitrate/nitrite-depleted beetroot juice. METHODS: Peripheral and central BP were assessed at heart-level in supine subjects using a brachial artery catheter and applanation tonometry, respectively. RESULTS: Nitrate/nitrite supplementation reduced peripheral systolic BP (148 ± 16 to 142 ± 18 mm Hg, P < 0.05) but not placebo (150 ± 19 to 149 ± 17 mm Hg, P = 0.93); however, diastolic BP was unaffected (supplement-by-time P = 0.08). Central systolic BP (131 ± 16 to 127 ± 17 mm Hg) and augmented pressure (13.3 ± 6.6 to 11.6 ± 6.9 mm Hg, both P < 0.05) were reduced after nitrate/nitrite, but not placebo (134 ± 17 to 135 ± 16 mm Hg, P = 0.62; 14.1 ± 6.6 to 15.2 ± 7.4 mm Hg, P = 0.20); central diastolic BP was unchanged by the interventions (supplement-by-time P = 0.16). Inorganic nitrate/nitrite also reduced AIx (24.3 ± 9.9% to 21.0 ± 9.6%) whereas no changes were observed following placebo (24.6 ± 9.3% to 25.6 ± 9.9%, P = 0.46). CONCLUSIONS: Inorganic nitrate/nitrite supplementation improves peripheral and central BP as well as AIx in T2DM. CLINICAL TRIALS REGISTRATION: Trial Number NCT02804932.

Continuous Positive Airway Pressure Adherence and Treatment Cost in Patients With Obstructive Sleep Apnea and Cardiovascular Disease.

Objective: To determine whether continuous positive airway pressure (CPAP) adherence reduces health care-related costs or use in patients with obstructive sleep apnea (OSA) and comorbid cardiovascular disease (CVD). Patients: A total of 23 million patients with CVD were identified in the Medicare fee-for-service database. Of the 65,198 who completed a sleep study between January 2016 and September 2018, 55,125 were diagnosed as having OSA and 1758 were identified in the 5% Medicare durable medical equipment (DME) database. Methods: Patients with DME claims were categorized as adherent (AD, treatment evidenced ≥91 days after CPAP initiation; n=614) or nonadherent (nAD, n=242) to CPAP therapy. In addition, 9881 individuals with CVD who were not diagnosed as having OSA after sleep testing and without CPAP initiation were included as control patients. Propensity score matching balanced the groups for age, sex, and comorbidities (eg, diabetes mellitus), resulting in 241 participants per cohort. Dependent variables included total episode-of-care, inpatient, outpatient, skilled nursing, home health, and DME costs across 12 months. Results: Total episode-of-care costs of AD participants ($6825) were lower than those of nAD ($11,312; P<.05) and control ($8102) participants. This difference (Δ) was attributable to fewer outpatient expenses (Δ$2290; P<.05) relative to the nAD group and fewer inpatient expenses (Δ$745) relative to the control group because skilled nursing costs were comparable between groups (P=.73). Conclusion: Adherence to CPAP treatment reduces annual health care-related expenses by 40% in Medicare patients with CVD and OSA.

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.

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.

Sleep Duration and Hypertension: Epidemiological Evidence and Underlying Mechanisms.

While the contribution of several physiological systems to arterial blood pressure regulation has been studied extensively, the role of normal and disrupted sleep as a modifiable determinant of blood pressure control, and in the pathophysiology of hypertension, has only recently emerged. Several sleep disorders, including sleep apnea and insomnia, are thought to contribute to the development of hypertension, although less attention is paid to the relationship between sleep duration and blood pressure independent of sleep disorders per se. Accordingly, this review focuses principally on the physiology of sleep and the consequences of abnormal sleep duration both experimentally and at the population level. Clinical implications for patients with insomnia who may or may not have abbreviated sleep duration are explored. As a corollary, we further review studies of the effects of sleep extension on blood pressure regulation. We also discuss epidemiological evidence suggesting that long sleep may also be associated with hypertension and describe the parabolic relationship between total sleep time and blood pressure. We conclude by highlighting gaps in the literature regarding the potential role of gut microbial health in the cross-communication of lifestyle patterns (exercise, diet, and sleep) with blood pressure regulation. Additionally, we discuss populations at increased risk of short sleep, and specifically the need to understand mechanisms and therapeutic opportunities in women, pregnancy, the elderly, and in African Americans.

Excessive Daytime Sleepiness and Cardiovascular Mortality in US Adults: A NHANES 2005-2008 Follow-Up Study.

PURPOSE: Excessive daytime sleepiness is highly prevalent and has been associated with increased risk of cardiovascular diseases, but evidence for its association with cardiovascular mortality is limited and inconsistent. We aimed to determine whether excessive daytime sleepiness is independently associated with cardiovascular mortality in general adult population. PATIENTS AND METHODS: A prospective study of 10,330 adult participants (aged ≥20 years) from National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2008 was followed up until December 31st, 2015. Excessive daytime sleepiness was defined as the self-reported feeling of being overly sleepy often or always during the day. Cox proportional hazard ratios (HRs) with 95% confidence interval (CI) were estimated to assess risk for cardiovascular mortality. RESULTS: A total of 10,330 participants with mean age of 47.3 years (95% CI, 46.0 to 48.1) were included in this analysis. Approximately, 18.5% of US adults reported excessive daytime sleepiness. Over a mean follow-up of 8.3 years, 262 cardiovascular deaths occurred. Participants with excessive daytime sleepiness had 2.85-times greater risk (95% CI, 1.33-6.09) of cardiovascular death than those without daytime sleepiness in multivariable analysis corrected for sociodemographic factors, comorbidities and cardiovascular risk factors including depression. Further adjustment for self-reported sleep disorders and sleep duration only slightly attenuated this association (HR, 2.55; 95% CI, 1.23-5.27). No interactions between excessive daytime sleepiness and age, sex or cardiovascular disease at study entry were observed (all Ps>0.05). CONCLUSION: Excessive daytime sleepiness is highly prevalent among US adults and is independently associated with an approximately two-and-a-half-fold increased risk of cardiovascular mortality in a large national sample. Screening for excessive daytime sleepiness may be a simple and cost-effective tool for identifying individuals at high risk of cardiovascular death.

Individual versus Group Calibration of Machine Learning Models for Physical Activity Assessment Using Body-Worn Accelerometers.

PURPOSE: We sought to determine if individually calibrated machine learning models yielded higher accuracy than a group calibration approach for physical activity intensity assessment. METHODS: Participants (n = 48) wore accelerometers on the right hip and nondominant wrist while performing activities of daily living in a semistructured laboratory and/or free-living setting. Criterion measures of activity intensity (sedentary, light, moderate, vigorous) were determined using direct observation. Data were reintegrated into 30-s epochs, and eight random forest models were created to determine physical activity intensity by using all possible conditions of training data (individual vs group), protocol (laboratory vs free-living), and placement (hip vs wrist). A 2 × 2 × 2 repeated-measures analysis of variance was used to compare epoch-level accuracy statistics (% accuracy, kappa [κ]) of the models when used to determine activity intensity in an independent sample of free-living participants. RESULTS: Main effects were significant for the type of training data (group: accuracy = 80%, κ = 0.59; individual: accuracy = 74% [P = 0.02], κ = 0.50 [P = 0.01]) and protocol (free-living: accuracy = 81%, κ = 0.63; laboratory: accuracy = 74% [P = 0.04], κ = 0.47 [P < 0.01]). Main effects were not significant for placement (hip: accuracy = 79%, κ = 0.58; wrist: accuracy = 75% [P = 0.18]; κ = 0.52 [P = 0.18]). Point estimates for mean absolute error were generally lowest for the group training, free-living protocol, and hip placement. CONCLUSIONS: Contrary to expectations, individually calibrated machine learning models yielded poorer accuracy than a traditional group approach. In addition, models should be developed in free-living settings when possible to optimize predictive accuracy.

Glycemic management is inversely related to skeletal muscle microvascular endothelial function in patients with type 2 diabetes.

Microvascular endothelial dysfunction precipitates cardiovascular disease mortality in patients with type 2 diabetes mellitus (T2DM). However, the relationship between glycemic management and microvascular endothelial function of these patients remains ill defined. We investigated the association between skeletal muscle microvascular endothelial function with glycemic management (HbA1c) and responses to an oral glucose challenge (OGTT) in 30 patients with T2DM (59 ± 9 years, 31.2 ± 5.1 kg/m2 , HbA1c = 7.3 ± 1.3%). On study day 1, microvascular endothelial function was quantified as the increase (Δ from rest) in forearm vascular conductance (FVC, ml/min/100 mmHg) during intra-arterial acetylcholine infusion at 4.0 and 8.0 µg/dl forearm volume/min (ACh4 and ACh8, respectively). [Glucose] and [insulin] were measured in a fasted state as well as following a 75 g OGTT on a second day with an additional fasting blood sample collected to measure HbA1c. FVC increased (Δ) 221 ± 118 and 251 ± 144 ml/min/100 mm Hg during ACh4 and ACh8 trials, respectively (p < 0.05 between doses). [Glucose] and [insulin] increased at the 1-h time point, relative to fasting levels, and remained elevated 2 h post-consumption (p < 0.05 for both variables and time points). [Glucose] nor [insulin], fasting or during the OGTT, were associated with ΔFVC during ACh4 or ACh8, respectively (p = 0.11-0.86), although HbA1c was inversely related (r = -0.47 and -0.46, respectively, p < 0.01 for both). Patients whose HbA1c met the ADA's therapeutic target of ≤7.0% had greater ΔFVC to ACh4 (272 ± 147 vs. 182 ± 74 ml/100 mm Hg/min) and ACh8 (324 ± 171 vs. 196 ± 90 ml/100 mm Hg/min, p < 0.05 for both trials) compared to those with >7.0%, respectively. Our data show glycemic management is related to acetylcholine-mediated vasodilation (e.g., microvascular endothelial function) in skeletal muscle of patients with T2DM.

Obstructive Sleep Apnea as a Cardiovascular Risk Factor-Beyond CPAP.

Patients with obstructive sleep apnea (OSA) experience repetitive partial or complete airway collapse during sleep resulting in nocturnal hypoxia-normoxia cycling, and are at increased cardiovascular risk. The number of apneas and hypopneas indexed per hour of sleep (apnea-hypopnea index) along with the associated intermittent hypoxia predict the increased cardiovascular risk; thus, their attenuation or prevention are objectives of OSA therapy. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA and, when effective, mitigates the apnea-hypopnea index and hypoxemia. As such, it is reasonable to expect CPAP would decrease cardiovascular risk. However, 3 recent randomized clinical trials of CPAP vs usual care did not show any significant effects of CPAP in attenuating incident cardiovascular events in patients with OSA. In this review, we discuss these studies in addition to potential complementary therapeutic options to CPAP (eg, neurostimulation) and conclude with suggested therapeutic targets for future interventional studies (eg, the autonomic nervous system). Although these areas of research are exciting, they have yet to be tested to any similar degree of rigour as CPAP.

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.

Waist-To-Hip Ratio Predicts Abnormal Overnight Oximetry in Men Independent of Body Mass Index.

Background: Ambulatory overnight oximetry (OXI) has emerged as a cost-effective initial test for sleep disordered breathing. Obesity is closely associated with obstructive sleep apnea (OSA); however, whether body mass index (BMI) or waist-to-hip ratio (WHR) predicts abnormal overnight OXI remains unknown. Methods: We performed a retrospective cross-sectional study of 393 men seen in the Executive Health Program at Mayo Clinic in Rochester, Minnesota who underwent ambulatory overnight OXI ordered by preventive medicine physicians between January 1, 2004 through December 31, 2010. We compared participant/spouse-reported symptoms (sleepiness, snoring), physician indications for OXI (obesity, fatigue), Epworth Sleepiness Scale scores, anthropomorphic measurements (WHR, BMI), and comorbid medical conditions (hypertension, diabetes) with OXI results. Results: 295 of the 393 men who completed OXI had abnormal results. During multivariate analysis, the strongest independent predictor of abnormal OXI for men was WHR (≥1.0, OR = 5.59) followed by BMI (≥30.0 kg/m2, OR = 2.75), age (≥55 yrs, OR = 2.06), and the presence of snoring (OR = 1.91, P < 0.05 for all). A strong association was observed between WHR and abnormal OXI in obese (BMI ≥ 30.0 kg/m2, OR = 6.28) and non-obese (BMI < 29.9 kg/m2, OR = 6.42, P < 0.01 for both) men. Furthermore, 88 men with abnormal OXI underwent polysomnography with 91% being subsequently diagnosed with OSA. Conclusions: In ambulatory, predominantly middle-aged men undergoing preventive services evaluation many physician indications for OXI were not predictors of abnormal results; however, WHR strongly predicted abnormal OXI in obese and non-obese men. As such, we suggest middle-aged men who snore and have a WHR ≥1.0 should be directly referred to a sleep clinic for polysomnography.