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The purpose of this study was to examine whether using both objectively (accelerometer) and subjectively (questionnaire) measured moderate- to vigorous-intensity physical activity (MVPA) and sedentary time (SED) improves the prediction of prediabetes and type 2 diabetes (pre/T2D) using data from the Framingham Heart Study ( n = 4200). Logistic regression was used to examine the odds ratio of pre/T2D in groups cross-classified by subjective and objective MVPA and SED. Less than half of participants fell into concordant categories of MVPA and SED using subjective and objective measures, with 7.0%–9.4% of participants in the extreme discordant categories of high-low or low-high subjective–objective MVPA or SED. Low objective MVPA, regardless of subjective MVPA status, was associated with a higher prevalence of pre/T2D ( P

A wide range of negative health outcomes have been associated with shift work (SW) particularly night and rotating SW. However, little is known about effects of SW exposure on reproductive health outcomes. The objective of our study is to prospectively investigate the association between SW exposure and the variations in age at natural menopause among adult Canadian workers.Secondary data analyses were performed using the Canadian Longitudinal Study on Aging database. Premenopausal women (N = 3,688) at baseline were followed prospectively for 3 years. Three derived variables were used to measure SW primary exposure: 1) ever exposed to SW, 2) SW exposure in current job, and 3) SW exposure in the longest job. Cox proportional hazard regression models were used to evaluate risk of variations in age at natural menopause after adjusting for potential confounders.One out of five women (20%) reported to be ever exposed to SW during their jobs. Overall, women who were ever exposed to SW were significantly associated with a delayed onset of menopause compared with daytime workers (hazard ratios [HR] = 0.77, 95% CI, 0.61-0.98). Particularly, when compared with daytime workers, rotating shift worker in the current and longest job were significantly related to delayed onset of menopause (HR = 0.64, 95% CI, 0.46-0.89 and HR = 0.65, 95% CI, 0.49-0.86), respectively.Our results suggest a relationship between rotating shift and delayed onset of menopause. We speculate that disruptive circadian stimuli may play a role in menopausal onset and this warrants further investigation.Video Summary:http://links.lww.com/MENO/A940 .

Women have been shown to experience blunted metaboreflex activation compared to men (Jarvis et al., 2011; Joshi & Edgell, 2019; Minahan et al., 2018; Samora et al., 2020), which may derive from altered autonomic balance. Since heart rate variability (HRV) estimates sympathetic and parasympathetic outflow, this study aims to determine if there are sex differences in HRV during metaboreflex activation. High frequency (HF) power and greater RR interval variability (SDRR) represent cardiac parasympathetic outflow, whereas the ratio between low frequency (LF) and HF power (LF/HF) represents cardiac sympathetic outflow. Thirty-two young, healthy men (n=16) and women (n=16) were recruited to perform 2mins of isometric handgrip at 40% of their maximal voluntary contraction followed by 3mins of post-exercise circulatory occlusion (PECO). ECG was continuously recorded, and HRV analysis was determined using 3mins of ECG at baseline or PECO. In response to PECO, heart rate (Women 71±12bpm vs. 73±13bpm; Men 68±12bpm vs. 72±13bpm; p=0.026) and mean arterial pressure (Women 84±8mmHg vs. 93±10mmHg; Men 85±9mmHg vs. 97±11mmHg; p0.07). At all timepoints and compared to men, women had 1) significantly lower LF power (Women 19±10nu vs. 24±16nu; Men 42±21nu vs. 49±17nu; p0.2), and 4) lower LF/HF (Women 0.26±0.17 vs. 0.41±0.42; Men 1.01±0.90 vs. 1.34±1.30; p=0.002). Unlike previous findings, no sex differences were observed in the pressor response to metaboreflex activation. HRV did not differ in response to PECO in both sexes; however, women had greater cardiac parasympathetic dominance than men. Funding provided by Natural Sciences and Engineering Research Council of Canada 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.

The EndoPAT device (Itamar Medical) is used to determine endothelial function by using peripheral arterial tonometry during reactive hyperemia. It has been shown to be related to the gold standard non-invasive technique of flow-mediated dilation ultrasound assessment. These methodologies have technical requirements and/or ongoing operational costs that could be prohibitive to under-resourced clinics or researchers. We hypothesized that using a re-usable and cost-effective procedure of determining the reactive hyperemic response using piezo-electric pulse transducers (ADInstruments) would give similar results to the EndoPAT. Reactive hyperemia was induced by occluding blood flow to the forearm for 5 minutes using a blood pressure cuff inflated to +50mmHg above systolic blood pressure. The vascular response to the release of the occlusion was assessed using EndoPAT on the index fingers and using piezo-electric transducers on the middle fingers, concurrently. Twenty-five healthy participants (15 female; 31±12years) participated in the study. Participants refrained from caffeine, alcohol, fatty foods, smoking and strenuous exercise for at least 12 hours prior to testing. The EndoPAT reactive hyperemia index (RHI) was determined using proprietary software. The area under the curve (AUC) of the finger pulse waves from the piezoelectric pulse transducers was also determined. The ratio of the AUC of the peak hyperemic response (10s average) compared to the baseline period (3.5min) in the occluded arm was compared to the equivalent ratio in the control arm to determine the pulse-wave reactive hyperemia index (PWRHI). Univariate linear regression and correlation analysis was conducted between RHI and PWRHI. When comparing the two methods, Spearman’s r was 0.67 (p=0.0002) with a coefficient of determination of 0.58. We have found that the two methods correlate well to each other and the PWRHI technique has the potential to make microvascular assessments more accessible to clinicians and researchers. Our PWRHI method still needs to be validated in larger populations with vascular dysfunction and over a wider age-range. Funding provided by the Natural Sciences and Engineering Research Council of Canada. 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.

STUDY OBJECTIVES: Adults with obesity and obstructive sleep apnea (OSA) are at risk for cardiometabolic disease, and this risk likely extends to children with both conditions. Noninvasive ventilation (NIV; including continuous and bilevel positive airway pressure) is often used to treat OSA in children with obesity. The aim of this study was to examine the impact of NIV treatment on heart rate variability (HRV), as a marker of cardiovascular risk, in children with obesity and newly diagnosed OSA. METHODS: A prospective multicenter cohort study was conducted in children with obesity prescribed NIV therapy for newly diagnosed moderate-severe OSA. Measurements of HRV were derived from polysomnography recordings at baseline and after 12 months of treatment. HRV parameters were examined by sleep stage, before and after arousal and oxygen desaturation events. HRV parameters were compared between time points using pair t tests as well as mixed model analysis. RESULTS: Twelve children had appropriate data for analysis at baseline and 12 months. Heart rate decreased by 4.5 beats/min after NIV treatment, with no change in HRV parameters. HRV parameters differed by sleep stage and showed an increase in arousal-related sympathetic-parasympathetic balance after 12 months of NIV treatment. HRV parameters did not differ before and after oxygen desaturation events. CONCLUSIONS: NIV for the treatment in children with obesity and OSA resulted in a small decrease in heart rate and an increase in arousal-related sympathetic-parasympathetic balance. These findings suggest small, potentially positive impacts of NIV on cardiovascular risk in children with concurrent obesity and OSA. CITATION: Kirk VG, Edgell H, Joshi H, et al. Cardiovascular changes in children with obstructive sleep apnea and obesity after treatment with noninvasive ventilation. J Clin Sleep Med. 2020;16(12):2063–2071.

Background: It is unclear whether the coronary microvascular responses to multiple, mechanistically distinct hyperaemic agents exert similar dilatory responses or share common clinical predictors. This study therefore sought to characterize the index of microvascular resistance (IMR) response to multiple hyperaemic agents in the human coronary circulation. Methods: Thermodilution-derived IMR was determined during intravenous adenosine, intracoronary acetylcholine, and intravenous dobutamine in patients with ischemic symptoms and nonobstructive coronary angiograms. A total of 128 patients were studied (44 with adenosine and acetylcholine, and 84 with all agents). Adenosine IMR >25, acetylcholine IMR >31, and dobutamine IMR >29 were used to define elevated responses. Results: IMR responses demonstrated weak-to-moderate association (adenosine vs acetylcholine IMR: ρ = 0.33; adenosine vs dobutamine IMR: ρ = 0.51; acetylcholine vs dobutamine IMR: ρ = 0.28; all P < 0.01). Logistic regression analyses revealed that: (1) elevated adenosine IMR was associated with increasing age and left ventricle hypertrophy (odds ratio [OR] = 1.27 and 1.58; both P < 0.05, respectively), (2) elevated acetylcholine IMR was associated with increasing plasma uric acid (OR = 1.09; P < 0.05), and (3) elevated dobutamine IMR was associated with hypertension and left atrial volume index (OR = 3.99 and 1.07; both P < 0.05, respectively). Subset analyses to evaluate clinical utility of the acetylcholine and dobutamine IMR, independent of abnormal adenosine IMR, revealed that elevated acetylcholine and/or dobutamine IMR were associated with higher risk exercise stress tests, left atrial volumes, and burden of exertional chest pain. Conclusions: Microvascular-specific IMR responses to different hyperaemic agents are only moderately associated, whereas the predictors for agent-specific IMR responses varied, suggesting that multiple pharmacologic agents interrogate different microvascular control mechanisms. Résumé: Contexte: On ne sait pas vraiment si les réponses microvasculaires coronariennes à de multiples agents hyperémiques aux modes d’action distincts ont des effets vasodilatateurs similaires ou partagent des facteurs prédictifs cliniques communs. Cette étude visait donc à caractériser la réponse selon l’indice de résistance microvasculaire (IMR) aux multiples agents hyperémiques dans la circulation coronarienne chez l’humain. Méhodologie: L’IMR obtenu par thermodilution a été déterminé pendant l’administration intraveineuse d’adénosine, intracoronarienne d’acétylcholine et intraveineuse de dobutamine chez des patients présentant des symptômes ischémiques et par angiogrammes coronariens non obstructifs. Un total de 128 patients (44 avec l’adénosine et l’acétylcholine, et 84 avec tous les agents) ont fait partie de l’étude. Des réponses élevées étaient définies par un IMR à l’adénosine > 25, un IMR à l’acétylcholine > 31 et un IMR à la dobutamine > 29. Résultats: Les réponses selon l’IMR ont révélé une association faible à modérée (IMR à l’adénosine vs IMR à l’acétylcholine : ρ = 0,33; IMR à l’adénosine vs IMR à la dobutamine : ρ = 0,51; IMR à l’acétylcholine vs IMR à la dobutamine : ρ = 0,28; tous : p < 0,01). Des analyses de régression logistique ont révélé que : 1) un IMR à l’adénosine élevé était associé à l’avancement en âge et à une hypertrophie ventriculaire gauche (rapport des cotes [RC] = 1,27 et 1,58; p < 0,05 respectivement pour les deux), 2) un IMR à l’acétylcholine élevé était associé à l’augmentation de la concentration plasmatique d’acide urique (RC = 1,09; p < 0,05) et 3) un IMR à la dobutamine élevé était associé à l’hypertension et à l’indice de volume auriculaire gauche (RC = 3,99 et 1,07; p < 0,05 respectivement pour les deux). Des analyses par sous-groupes visant à évaluer l’utilité clinique de l’IMR à l’acétylcholine et à la dobutamine, indépendamment d’un IMR à l’adénosine anormal, ont révélé que des IMR à l’acétylcholine et/ou à la dobutamine élevés étaient associés à une augmentation du risque lors des épreuves à l’effort, à un volume auriculaire gauche plus élevé et à une augmentation du fardeau associé à la douleur thoracique à l’effort. Conclusions: Les réponses microvasculaires selon l’IMR à différents agents hyperémiques sont seulement modérément associées, alors que les facteurs prédictifs des réponses selon l’IMR spécifique de l’agent varient, ce qui laisse croire que les multiples agents pharmacologiques font appel à différents mécanismes de contrôle microvasculaire.

Objective The age at natural menopause has subsequent health implications. Earlier age at natural menopause is a risk factor for cardiovascular disease, atherosclerosis, and stroke. Despite extensive study, no clear and conclusive association between anthropometric measures and age at natural menopause has emerged. This study aims to assess whether baseline and/or longitudinal changes in adiposity are associated with age at natural menopause. Methods In all, 2,030 premenopausal women from the Coronary Artery Risk Development in Young Adults study-a prospective study with 25 years follow-up-were included for analysis from 1985 to 1986 until menopause was attained. Anthropometry included body mass index and waist circumference. Discrete-time survival analysis was then used to determine the association between anthropometric measures at baseline, and also their changes with age at natural menopause, while adjusting for various time-varying and invariant covariates in separate models for body mass index and waist circumference. Results Multivariate Cox regression analysis showed that baseline body mass index (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.94-0.98) and baseline waist circumference (HR 0.98, 95% CI 0.97-0.99) significantly increased the risk of later age at natural menopause. Neither time-varying body mass index nor waist circumference indicating change across time associated with age at natural menopause. Premenopausal hypertension was strongly associated with an earlier age at natural menopause. Conclusion These findings show that age at natural menopause is partly determined by modifiable factors such as premenopausal hypertension and baseline adiposity. These results highlight the importance of both control and prevention of cardiovascular risk factors such as excess weight in early to mid-adulthood before menopause onset.

Women display an attenuated mechanoreflex during leg movement; however, sex differences in the response to arm movement are unknown. Men (n = 12) and women (n = 10) performed passive arm or leg movement where either the right elbow or right knee was passively flexed/extended for 3 min at 30 times/min. Mean arterial pressure (MAP), cardiac output index (Qi), and heart rate (HR) were continuously measured and 1-min averages along with peak values were obtained. Heart rate variability was measured at baseline and throughout 3 min of passive movement. Men had a greater average HR (P = 0.006) and Qi (P = 0.05) responses to passive limb movement compared to women. Men also had a greater (P = 0.02) and faster (P = 0.04) peak Qi response compared to women. During arm movement, men exhibited a greater change of average MAP compared to both women (P = 0.002) and leg movement (P = 0.05). Movement of either limb in both sexes decreased low-frequency power (LF; P = 0.04), decreased low-frequency to high-frequency ratio (LF/HF; P = 0.03), and increased high-frequency power (HF; P = 0.01) of heart rate variability. Women had lower pulse wave velocity (P = 0.02), higher root mean square of the successive differences (RMSSD; P = 0.04), lower LF power (P = 0.04), higher HF power (P = 0.03), and higher cardiovagal baroreceptor sensitivity (P = 0.003) compared to men at all time points. We have found sex- and limb-dependent responses where men exhibit higher blood pressure in response to passive arm movement compared to women and compared to leg movement.

Background The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD. Methods In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia. Results LnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P P P = 0.34). Conclusions CMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

Head-down bed rest (HDBR) has previously been shown to alter cerebrovascular and autonomic control. Previous work found that sustained HDBR (≥ 20 days) attenuates the hypercapnic ventilatory response (HCVR); however, little is known about shorter-term effects of HDBR nor the influence of HDBR on the hypoxic ventilatory response (HVR). We investigated the effect of 4-h HDBR on HCVR and HVR and hypothesized attenuated ventilatory responses due to greater carotid and brain blood flow. Cardiorespiratory responses of young men (n = 11) and women (n = 3) to 5% CO2 or 10% O2 before and after 4-h HDBR were examined. HDBR resulted in lower HR, lower cardiac output index, lower common carotid artery flow, higher SpO2, and higher pulse wave velocity. After HDBR, tidal volume and ventilation responses to 5% CO2 were enhanced (all P 0.05). Short-duration HDBR does not alter the HVR, yet enhances the HCVR, which we hypothesize is a consequence of cephalic CO2 accumulation from cerebral congestion.

Progesterone and its analogues are known to influence ventilation. Therefore, the purpose of this study was to investigate the role of endogenous and pharmaceutical female sex hormones in ventilatory control during the activation of the metaboreflex, mechanoreflex, and CO2 chemoreflex. Women aged 18–30 taking (n = 14) or not taking (n = 12) oral contraceptives (OC and NOC, respectively) were tested in the low hormone (LH) and high hormone (HH) conditions corresponding to the early follicular and mid‐luteal phases (NOC) or placebo and high‐dose pills (OC). Women underwent three randomized trials: (a) 3 min of passive leg movement (PLM), (b) 2 min of 40% maximal voluntary handgrip exercise followed by 2 min of post‐exercise circulatory occlusion (PECO), and (c) 5 min of breathing 5% CO2. We primarily measured hemodynamics and ventilation. During PLM, the OC group had a smaller pressor response (p = .012). During PECO, the OC group similarly exhibited a smaller pressor response (p = .043) and also exhibited a greater ventilatory response (p = .024). Lastly, in response to breathing 5% CO2, women in the HH phase had a greater ventilatory response (p = .022). We found that OC use attenuates the pressor response to both the metaboreflex and mechanoreflex while increasing the ventilatory response to metaboreflex activation. We also found evidence of an enhanced CO2 chemoreflex in the HH phase. We hypothesize that OC effects are from the chronic upregulation of pulmonary and vascular β‐adrenergic receptors. We further suggest that the increased cyclic progesterone in the HH phase enhances the chemoreflex., We have shown that natural and pharmaceutical female sex hormones can influence the metaboreflex, mechanoreflex, and CO2 chemoreflex. Oral contraceptives users have attenuated pressor responses to both metaboreflex and mechanoreflex activation concurrent with augmented ventilatory responses to metaboreflex activation. Women in the high hormone phase of the menstrual cycle have a greater ventilatory response to CO2 compared to the low hormone phase.

Postural orthostatic tachycardia syndrome (POTS) is accompanied by reduced brain blood flow, autonomic dysfunction, and orthostatic intolerance. We hypothesized that wearing a neck compression collar would attenuate orthostatic symptoms, increase brain blood flow, and influence autonomic reflexes. Ten participants with POTS (9 women, age: 36 ± 10) underwent two trials of supine rest, paced deep breathing (6 breaths/min), Valsalva maneuver (40 mmHg for 15 s), and 70° upright tilt. For one trial, participants wore a neck compression device (Q30 Innovations). Blood pressure, heart rate (HR), brain blood flow velocity, stroke volume, respiratory rate, and end-tidal gases were continuously measured. The Vanderbilt Orthostatic Symptom Score was compiled at the end of tilt. The use of the collar reduced the orthostatic symptom score of participants with POTS during upright tilt (26.9 ± 12.5 to 18.7 ± 13.1, P = 0.04). Collar compression in the supine condition reduced the low-frequency domain of HR variability (60 ± 18 to 51 ± 23 normalized units, P = 0.04) and increased the change in HR (15 ± 5 to 17 ± 6 bpm, P = 0.02) and E:I ratio (1.2 ± 0.1 to 1.3 ± 0.1, P = 0.01) during paced deep breathing. Throughout tilt, wearing the collar reduced respiratory rate (baseline: 13 ± 3 to 12 ± 4 breath/min; tilt: 18 ± 5 to 15 ± 5 breath/min; main effect of collar P = 0.048), end-tidal oxygen (baseline: 115 ± 5 to 112 ± 5 mmHg; tilt: 122 ± 10 to 118 ± 11 mmHg; main effect of collar P = 0.026). In participants with POTS, wearing the Q-collar reduced orthostatic symptoms, increased the HR response to deep breathing, and decreased resting ventilation. NEW & NOTEWORTHY We found that using a neck compression collar alleviated orthostatic symptoms in upright posture in participants with postural orthostatic tachycardia syndrome (POTS). This could be due to compression of the baroreceptors and subsequent changes in autonomic function. Indeed, we observed increased heart rate responsiveness to paced deep breathing and reductions of respiratory rate and end-tidal O2 (suggesting reduced ventilation). Further, wearing the collar reduced mean blood velocity in the brain during Valsalva perhaps due to higher brain blood volume.

Reactive hyperemia peripheral arterial tonometry and flow-mediated dilation are common noninvasive measures of peripheral vascular function. However, their relationship with the coronary circulation, particularly in coronary microvascular dysfunction (CMD), is unclear. Therefore, the purpose of this study is to compare these noninvasive measurements with coronary microvascular function after endothelial-independent, endothelial-dependent, and sympathetically mediated pharmacologic hyperemia.Forty-seven patients with suspected CMD completed peripheral and coronary assessments. The reactive hyperemia index was collected using the EndoPAT2000 device, whereas a subset of patients (n = 28) completed brachial artery flow-mediated dilation using duplex ultrasound. Coronary microvascular function was quantified using the resistance and flow responses to intravenous adenosine (140 μg/kg/min), dobutamine (40 μg/kg/min), and intracoronary acetylcholine (100 μg). Abnormal coronary microvascular responses to adenosine and/or acetylcholine were used to define CMD.The reactive hyperemia index (No CMD: 0.85 ± 0.23 vs CMD: 0.61 ± 0.26, P0.05) and flow-mediated dilation (No CMD: 7.2 ± 2.3 vs CMD: 4.8 ± 3.1; P0.05) were attenuated in patients with CMD. Whereas the reactive hyperemia index was correlated with the resistance and flow responses to dobutamine (ρ = -0.44 and ρ = 0.39, respectively; P0.05), flow-mediated dilation was correlated with the resistance responses to both adenosine (ρ = -0.48; P0.05) and acetylcholine (ρ = -0.66; P0.05). Lastly, the reactive hyperemia index and flow-mediated dilation had sensitivities of 80% and 69% and specificities of 71% and 93%, respectively, for identifying patients with CMD.Peripheral vascular function is attenuated in CMD, and noninvasive measurements are associated with coronary responses to pharmaceutical stimulation.

Sex differences in the regulation of autonomic and cerebrovascular responses to orthostatic stress remain unclear. The objectives of this study were to concurrently investigate autonomic control and cerebrovascular resistance indices, including critical closing pressure (CrCP) and resistance area product (RAP), during upright tilt in men and women. In 13 women and 14 men (18–29 years), ECG, non-invasive blood pressure, middle cerebral artery blood velocity, and end-tidal CO2 (ETCO2) were continuously measured during supine rest and 70° tilt. Heart rate variability (HRV), cardiovagal baroreflex sensitivity (cBRS), and transfer function parameters of dynamic cerebral autoregulation were calculated. Compared to supine, upright tilt increased the low frequency-to-high frequency ratio of HRV in men only (P = 0.044), and decreased cBRS more in women (P = 0.001). Cerebrovascular resistance index (CVRi) increased during tilt only in men (sex-by-time interaction: P = 0.004). RAP was lower in women throughout tilt (main effect of sex: P = 0.022). CrCP decreased during tilt in both sexes (main effect of time: P

Asthma independently increases the risk of developing cardiovascular disease. As inhaled β-agonists have systemic cardiovascular effects, and elevations in arterial stiffness and sympathetic nerve activity are associated with increased cardiovascular morbidity/mortality, this study examines the effect of salbutamol use on pulse wave velocity (PWV) and muscle sympathetic nervous activity (MSNA). Healthy men and women (26.2±1.5years) were recruited for: Day 1: 4 inhalations of placebo followed by 4 inhalations of salbutamol (4×100μg); Day 2: placebo only; Day 3: carotid-femoral PWV measurements before/after placebo/salbutamol. Heart rate (HR), mean arterial pressure (MAP), and carotid-radial PWV were obtained on Day 1 and 2. MSNA was obtained on Day 1. Salbutamol increased HR and total MSNA (Baseline1: 2.8±2.8au; Placebo: 2.4±2.1au; Baseline2: 2.7±3.0au; Salbutamol: 3.3±2.9au; p=0.05), with no changes in MAP or PWV. There were no effects of placebo on HR, MSNA, or PWV. Acute salbutamol use increases sympathetic activity suggesting that salbutamol could contribute to cardiovascular morbidity/mortality in individuals using inhaled β-agonists.

ObjectiveNeck compression collars have been proposed to reduce injury to the brain caused by head impacts. Our objective was to test if compression of the carotid artery affected the baroreflex and influenced blood pressure control.MethodsCerebrovascular and autonomic responses of healthy young men and women (n = 8 each) to paced deep breathing, Valsalva, and 70o head-up tilt with or without use of a Q-collar were determined. Continuous measurements of heart rate, beat-to-beat blood pressure, transcranial Doppler, and end-tidal gases were obtained. Heart rate variability was measured during supine rest and head-up tilt. Carotid artery and jugular vein cross-sectional area were measured at end-inhalation and end-exhalation using cross-sectional ultrasound images at diastole.ResultsWearing the collar reduced carotid cross-sectional area (CSA; P = 0.022; η2 = 0.03) and increased jugular CSA (P = 0.001; η 2 = 0.30). In both men and women, wearing the collar increased systolic blood pressure during Valsalva (P0.05), and there were no effects of the collar on cerebrovascular function, hemodynamics, cardiovagal baroreceptor sensitivity, or heart rate variability (P>0.05) during upright tilt.ConclusionUse of the Q-collar compresses both the jugular vein and carotid artery influencing sympathetic nerve activity in both men and women while influencing brain blood flow in women.

After exposure to microgravity, or head‐down bed rest (HDBR), fluid loading is often used with the intent of increasing plasma volume and maintaining mean arterial pressure during orthostatic stress. Nine men (aged 18–32 years) underwent three randomized trials with lower body negative pressure (LBNP) before and after: (1) 4‐h of sitting with fluid loading (1 g sodium chloride/125 mL of water starting 2.5‐h before LBNP), (2) 28‐h of 6‐degree HDBR without fluid loading, and (3) 28‐h of 6‐degree HDBR with fluid loading. LBNP was progressive from 0 to −40 mmHg. After 28‐h HDBR, fluid loading did not protect against the loss of plasma volume (−280 ± 64 mL without fluid loading, −207 ± 86 with fluid loading, P = 0.472) nor did it protect against a drop of mean arterial pressure (P = 0.017) during LBNP (Post‐28 h HDBR response from 0 to −40 mmHg LBNP: 88 ± 4 to 85 ± 4 mmHg without fluid loading and 93 ± 4 to 88 ± 5 mmHg with fluid loading, P = 0.557 between trials). However, fluid loading did protect against the loss of stroke volume index and central venous pressure observed after 28‐h HDBR. Fluid loading also attenuated the increase of angiotensin II seen after 28‐h HDBR and throughout the LBNP protocol (Post‐28 h HDBR response from 0 to −40 mmHg LBNP: 16.6 ± 3.4 to 23.7 ± 5.0 pg/mL without fluid loading and 6.1 ± 0.8 to 12.2 ± 2.3 pg/mL with fluid loading, P

Introduction. One in three US adults is living with obesity or hypertension, and more than 75% of hypertensive individuals are using antihypertensive medications. Therefore, it is important to examine blood pressure (BP) differences in populations that are using these medications with differing obesity status. Aim. We examined whether BP attained when using various antihypertensive medications varies amongst different body mass index (BMI) categories and whether antihypertensive medication use is associated with differences in other metabolic risk factors, independent of BMI. Methods. Adults with hypertension from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 were used (n=15,285). Linear regression analyses were used to examine the main effects and interaction between antihypertensive use and BMI. Results. In general, users of antihypertensive medications had lower BP than those not taking BP medications (NoBPMed) (P<0.05), whereby in women, the differences in systolic BP between angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) users and NoBPMed were greater in those with obesity (ACE inhibitors: −14 ± 1 mmHg; ARB: −16 ± 1 mmHg) compared to normal weight individuals (ACE inhibitors: −9 ± 1 mmHg; ARB: −11 ± 1 mmHg) (P<0.05). Diastolic BP differences between women ARB users and NoBPMed were also greatest in obesity (−5 ± 1 mmHg) (P<0.05) whilst there were no differences in normal weight individuals (−1 ± 1 mmHg) (P>0.05). Furthermore, glucose levels and waist circumference in women were higher in those using ACE inhibitors compared to diuretics (P<0.05). Conclusion. ACE inhibitors and ARBs may be associated with more beneficial BP profiles in women with obesity, with no obesity-related BP differences for antihypertensive medication in men. However, there could be potential cardiometabolic effects for some antihypertensive medications that should be explored further.

Orthostatic intolerance is more common in women than men, and some studies have found that women in the early follicular (EF) phase of the menstrual cycle experience the greatest feelings of lightheadedness. Chemoreflex function while supine or upright was investigated to determine the potential contribution of ventilatory control to these phenomena. Men (n = 13) and women (n = 14) were tested while supine and 70° upright (head‐up tilt [HUT]) and given: (1) normoxia or (2) hypercapnia (5% CO2). Women were tested during the EF phase (days 2–5) and the midluteal phase (ML; days 18–24). During HUT, all groups reduced cerebrovascular resistance index (men: 1.45 ± 0.08 to 1.42 ± 0.07 mmHg/(cm·sec), EF: 1.38 ± 0.11 to 1.26 ± 0.10 mmHg/(cm·sec), ML: 1.25 ± 0.07 to 1.09 ± 0.07 mmHg/(cm·sec); P ≤ 0.019); however, only men increased ventilation (men: 11.99 ± 0.65 to 13.24 ± 0.83 L/min; P

Objective The aim of the study was to assess the prevalence and factors associated with hormone therapy (HT) use among Canadian women. Methods Baseline data from the Tracking cohort of the Canadian Longitudinal Study on Aging (CLSA) was used for this analysis. The main outcome was HT use among women aged 45-85 years, defined as current, past, and never users. Multinomial logistic regression models were used to examine the differences between current, past, and never HT users in terms of sociodemographic, health behavior, and health-related variables. Results Overall, 9.5% of the sample reported current use of HT, whereas 21.9% reported past use. The main factors associated with a lower likelihood of current HT use were older age (>80 y), nonwhite ethnic background, current employment, regular smoking, obesity, and breast cancer. By contrast, alcohol consumption, and the presence of allergies or mood disorders were positively associated with current HT use. Conclusions These findings provide a recent national picture of HT use in Canada that may be used to inform opportunities for improved physician-patient communication regarding menopause management.

Hormone replacement therapy (HRT) has been established as the first-line treatment for women experiencing menopausal symptoms. The use of complementary and alternative medicine (CAM), however, is becoming increasingly popular among women at midlife for management of such symptoms. Despite the equivocal evidence of CAM's efficacy in the reduction and alleviation of menopausal symptoms in placebo-controlled, randomized trials, 50% of women at midlife use CAM. To date, several large, population-based studies have focused upon CAM use amongst menopausal women and the factors associated with the adoption of such therapies. By identifying women in the menopausal transition who tend to use CAM, this narrative review highlights evidence that aids women at this stage of life make better and individualized treatment choices to relieve these symptoms. The available evidence suggests that the prevalence of CAM use among menopausal women is high world-wide, but there is a paucity of high-quality studies that adequately assess the factors associated with its use. Further studies are needed to confirm the characteristics of women who employ CAM to manage their night sweats and hot flushes. Results of this study might enable the development of policies catering to the needs of those women and provide a resource to support their decision-making regarding treatment options.

Deep breathing assesses autonomic function; however, many researchers/clinicians do not account for hyperventilation, brain blood flow or blood pressure. Men and women (with/without oral contraceptives) participated. women participated during low and high hormone phases of the menstrual cycle. Blood pressure, end-tidal carbon dioxide, middle cerebral artery velocity and cerebrovascular resistance were assessed. Deep breathing decreased end-tidal carbon dioxide and middle cerebral artery velocity while increasing cerebrovascular resistance in all participants; blood pressure decreased in men. There were no influences of menstrual cycle or oral contraceptives. Men have different autonomic responses to deep breathing compared to women.

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men ( n = 13, 25.8 ± 1.8 yr old) and women in the LH ( days 2–5; placebo) and HH ( days 18–24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO2, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men ( P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity ( P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures ( P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing ( P = 0.010). Only men experienced higher resistance index ( P < 0.001) and pulsatility index ( P < 0.001) with standing. The OC group had lower end-tidal CO2 ( P = 0.002) than the NOC group ( P = 0.030) and men ( P ≤ 0.067). SVi ( P = 0.004) and cardiac output index ( P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity ( P = 0.058) and higher SVi ( P = 0.059) and pulsatility index ( P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase ( P = 0.049) and lower in the HH than LH phase ( P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology. NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.

Recent work has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine whether the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (height: 177.0 ± 2.1 cm, weight: 85.8 ± 5.5 kg, age: 24.6 ± 1.1 yr) performed three trials of 40% maximal voluntary contraction handgrip for 2 min, followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SPo2 = 85%), or hyperoxia (FiO2 = 1.0) during the PECO to modulate the chemoreflex. After these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (V̇e), heart rate (HR), blood pressure, and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA ( P = 0.038) and HR ( P = 0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR ( P < 0.001) and V̇e ( P < 0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise.

The standard measurement of pulse wave velocity (PWV) is restricted by the need for simultaneous tonometry measurements requiring two technicians and expensive equipment, limiting this technique to well-resourced settings. In this preliminary study, we compared a simplified method of pulse wave detection from the finger and toe to pulse wave detection from the carotid and radial arteries using applanation tonometry in children and young adults. We hypothesized that the simplified method of PWV measurement would strongly correlate with the standard measurement in different age groups and oxygen conditions. Participants included (a) boys and girls aged 8-12 years and (b) men and women aged 18-40 years. Participants rested supine while carotid and radial artery pulse waves were measured using applanation tonometry and finger and toe pulse waves were simultaneously collected using a Finometer Midi and a piezo-electric pulse transducer, respectively. These measurements were repeated under hypoxic conditions. Finger-toe PWV measurements were strongly correlated to carotid-radial PWV in adults (R=0.58; P=0.011), but not in children (R=0.056; P=0.610). Finger-toe PWV was sensitive enough to show increases in PWV with age (P

Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart failure (HF), and sensitivity is linked to greater mortality. This study aimed to determine the role of the peripheral chemoreceptor in cardiovascular control at rest and during exercise in HF patients and controls. Clinically stable HF patients ( n = 11; ejection fraction: 39 ± 5%) and risk-matched controls ( n = 10; ejection fraction: 65 ± 2%) performed randomized trials with or without dopamine infusion (2 μg·min−1·kg−1) at rest and during 40% maximal voluntary contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100% oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral chemoreceptor. At rest in HF patients, dopamine decreased ventilation ( P = 0.02), decreased total peripheral resistance index ( P = 0.003), and increased cardiac and stroke indexes ( P ≤ 0.01), yet there was no effect of dopamine on these variables in controls ( P ≥ 0.7). Hyperoxia lowered ventilation in HF ( P = 0.01), but not in controls ( P = 0.9), indicating suppression of the peripheral chemoreceptors in HF. However, no decrease of total peripheral resistance index was observed in HF. As expected, HG increased heart rate, ventilation, and brachial conductance of the nonexercising arm in controls and HF patients. During dopamine infusion, there were no changes in mean arterial pressure, heart rate, or ventilation responses to HG in either group ( P ≥ 0.26); however, brachial conductance increased with dopamine in the control group ( P = 0.004), but decreased in HF ( P = 0.02). Our findings indicate that the peripheral chemoreceptor contributes to cardiovascular control at rest in HF patients and during exercise in risk-matched controls.

We tested the hypotheses that estrogen replacement in ovariectomized (OVX) rats attenuates cardiovascular responses to psychological stress and that nitric oxide (NO) in the brain mediates these effects. Female rats were OVX; one group received 17β-estradiol (OVX-E) for 11-12 days and the other received vehicle (OVX-V). Seven days after OVX, OVX-E and OVX-V rats were chronically instrumented for arterial pressure measurements and intracerebroventricular injections. Later (4-5 days), OVX-E and OVX-V rats received intracerebroventricular injections of NG-nitro-l-arginine (88 μg/kg), an inhibitor of constitutive NO production, or vehicle. Mean arterial pressure (MAP) and heart rate responses were then measured in conscious rats exposed to two cycles of 1-h restraint/1-h rest. We show that MAP responses in restrained OVX-E rats were attenuated both during restraint and during rest. Although inhibition of NO production in the brain had no effect on MAP responses to restraint in OVX-V rats, it augmented responses in restrained OVX-E rats, especially during periods of rest, so that MAPs in restrained OVX-E and OVX-V rats were indistinguishable. Finally, NO levels in hypothalami and brain stems were elevated in restrained OVX-E, but not OVX-V, rats compared with their respective unrestrained controls. These results show that estrogen replacement in OVX rats reduces arterial pressure responses to psychological stress and that these effects are mediated, at least in part, by NO.

COPD is associated with elevated cardiovascular risk and a potentiated ventilatory response to exercise. Enhanced carotid chemoreceptor (CC) activity/sensitivity is present in other clinical conditions, has been shown to contribute to sympathetic vasoconstrictor outflow, and is predictive of mortality. CC activity/sensitivity, and the resulting functional significance, has not been well examined in COPD. We hypothesized that CC activity/sensitivity would be elevated in COPD, and related to increased pulse wave velocity (a marker of CV risk) and the ventilatory response to exercise. Methods: 30 COPD patients and 10 healthy age-matched controls were examined. Participants performed baseline cardiopulmonary exercise and pulmonary function testing. CC activity was later evaluated by the drop in ventilation with breathing 100% O2, and CC sensitivity was then assessed by the ventilatory response to hypoxia (ΔVE/ΔSpO2). Peripheral arterial stiffness was subsequently evaluated by measurement of pulse wave velocity (PWV) using applanation tonometry while the subjects were breathing room air, and then following chemoreceptor inhibition by breathing 100% O2 for 2 minutes. Results: CC activity, CC sensitivity, PWV and the ventilatory response to exercise were all increased in COPD relative to controls. CC sensitivity was related to PWV; however, neither CC activity nor CC sensitivity was related to the ventilatory response to exercise in COPD. CC inhibition by breathing 100% O2 normalized PWV in COPD, while no effect was observed in controls. Conclusion: CC activity and sensitivity are elevated in COPD, and appear related to cardiovascular risk; however, CC activity/sensitivity does not contribute to the potentiated ventilatory response to exercise.

Cardiovascular deconditioning after a 4-h head-down bed rest (HDBR) might be a consequence of the time of day relative to pre-HDBR testing, or simply 4 h of confinement and inactivity rather than the posture change. Ten men and 11 women were studied during lower body negative pressure (LBNP) before and after 4-h HDBR and 4-h seated posture (SEAT) as a control for time of day and physical inactivity effects to test the hypotheses that cardiovascular deconditioning was a consequence of the HDBR posture, and that women would have a greater deconditioning response. Following HDBR, men and women had lower blood volume, higher heart rate with a greater increase during LBNP, a greater decrease of stroke volume during LBNP, lower central venous pressure, smaller inferior vena cava diameter, higher portal vein resistance index with a greater increase during LBNP, but lower forearm vascular resistance, lower norepinephrine, and lower renin. Women had lower vasopressin and men had higher vasopressin after HDBR, and women had lower pelvic impedance and men higher pelvic impedance. Following SEAT, brachial vascular resistance was reduced, thoracic impedance was elevated, the reduction of central venous pressure during LBNP was changed, women had higher angiotensin II whereas men had lower levels, and pelvic impedance increased in women and decreased in men. Cardiovascular deconditioning was greater after 4-h HDBR than after SEAT. Women and men had similar responses for most cardiovascular variables in the present study that tested the responses to LBNP after short-duration HDBR compared with a control condition.