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Objectives: The aim of the study is to determine if law enforcement officers develop subclinical atherosclerotic cardiovascular disease (ASCVD) earlier than nonofficers and, if so, the extent to which conventional risk factors explain this difference. Methods: Estimated pulse wave velocity (ePWV) was the marker of subclinical ASCVD. EPWV, ASCVD risk factors, metabolic syndrome (MetS), and 10-year risk for ASCVD were compared among 408 law enforcement officers and a civilian cohort. Results: EPWV, 10-year ASCVD risk, and MetS prevalence increased significantly with age. All but the officers age 55 and older had higher ePWV cohort than the civilian cohort ( P < 0.001). Ten-year ASCVD risk explained the most variability of ePWV ( R2 = 0.49, P < 0.001). Conclusions: Officers develop subclinical ASCVD earlier than nonofficers. Conventional ASCVD risk factors only explain about half of this increase. Occupational factors may play a role in contributing to this increased ASCVD risk., Competing Interests: Conflict of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes., Purpose: To assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow., Methods: Ten adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility., Results: Nine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges' g = 0.84-2.13). There were small-to-moderate increases in MCA velocity (g = 0.32-0.57) and conductance (g = 0.20-0.76) across time, with minimal changes in pulsatility (all g < 0.21)., Conclusions: Preliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET's efficacy for treating MDD via potential cerebrovascular mechanisms is warranted., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o 2peak ) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o 2peak increased 6% in AET and decreased 4% in CON ( P < 0.05). Proximal aortic compliance increased ( P = 0.04, partial η 2 = 0.14) and aortic characteristic impedance decreased ( P = 0.02, partial η 2  = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant ( P = 0.07, partial η 2  = 0.11) compared with CON. Working memory reaction time improved with AET but not CON ( P = 0.02, partial η 2  = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics. NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

Introduction: Regular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity., Methods: This prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0%-30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022., Results: Over an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0%-30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA., Conclusions: These results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia., (Copyright © 2024 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Mechanisms underlying sex differences in brain aging remain unclear but may relate to changes in cerebral pulsatile blood flow. Sex differences in the stiffening of the large arteries and expansion of pulse pressure with age may accelerate changes in pulsatile (i.e., discontinuous) blood flow in the brain that contribute to brain health. The purpose of this cross-sectional, secondary analysis was to examine sex differences in age-associated changes in large artery (aorta and carotid) stiffness, carotid pulse pressure, and cerebral pulsatility in 206 men and 217 women between 18 and 72 yr of age. Outcomes included aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] and carotid pulse pressure via tonometry, carotid β-stiffness via ultrasound, and middle cerebral artery (MCA) pulsatility index via transcranial Doppler. Regression analyses revealed a significant age-by-sex interaction, with women exhibiting a slower rate of change compared with men for cfPWV (β = -0.21, P = 0.04), and greater rate of change for carotid stiffness (β = 0.27, P = 0.02), carotid pulse pressure (β = 0.98, P < 0.001), and MCA pulsatility index (β = 0.49, P = 0.002) after adjustment for covariates. The significant age-by-sex interaction for MCA pulsatility was abolished after further adjustment for carotid pulse pressure. Women exhibit accelerated increases in cerebral pulsatility during midlife, likely driven by exaggerated increases in carotid stiffness and pulse pressure compared with men. These data suggest that there are disproportionate increases in cerebral pulsatility in women during midlife that could contribute to accelerated brain aging compared with men. NEW & NOTEWORTHY We identify sex-specific associations between increasing age and cerebral pulsatility and its vascular mechanisms. When compared with men, women in our cross-sectional analysis exhibited greater age-associated increases in carotid stiffness, carotid pulse pressure, and cerebral pulsatility particularly during midlife. These data suggest that the rapid expansion of pulse pressure during midlife contributes to an exaggerated increase in cerebral pulsatility among women and suggest a potential mechanism contributing to sex differences in brain aging.

Acute exercise has been shown to transiently improve specific aspects of cognitive function, however the mechanism governing these effects remain unclear. Blood pressure responses during exercise have been hypothesized to be a primary contributing factor, in part through its influence on cerebral blood flow. In this counterpoint, we highlight the inconsistent and weak associations between changes in blood pressure, cerebral blood flow and cognitive responses during and following acute exercise. Despite sound theoretical foundation, cognitive responses to exercise do not appear strongly related to blood pressure and more likely stem from a complex integration of multiple mechanisms.

Background: Carotid-femoral pulse wave velocity (cfPWV), the referent measure of aortic stiffness, is an established measure of vascular aging. In studies where cfPWV cannot be measured, alternative methods are needed to help promote research on vascular aging. This study examines the construct validity of a measure of PWV estimated from age and blood pressure (ePWV). The specific aims of the study are to: 1) explore the strength of association between ePWV, cfPWV, and other established measures of vascular aging; 2) examine the sensitivity and specificity of elevated ePWV (≥10m/s) in relation to elevated cfPWV (≥10m/s)., Methods: We measured cfPWV in two-hundred and fifty-two adults (mean age 57±12 years, 48% female) and calculated each participant's ePWV from their age and brachial blood pressure. Additional measures of vascular aging included: carotid intima-media thickness (cIMT); carotid stiffness measured as elastic modulus (cEp); and carotid augmentation index (cAIx)., Results: The correlations between cfPWV and measures of vascular aging were: cEp (r = 0.36), cIMT (r = 0.49), and cAIx (r = 0.04). The correlations between ePWV and measures of vascular aging were: cEp (r = 0.45), cIMT (r = 0.60), and cAIx (r = 0.24). The correlation between ePWV and cfPWV was (r = 0.67). The sensitivity and specificity of elevated ePWV (≥ 10 m/s) for concomitantly identifying high cfPWV (≥ 10 m/s) were 85.4% and 73.0% respectively., Conclusion: ePWV is associated with established measures of vascular aging, such as carotid thickness, carotid stiffness and carotid augmentation index. ePWV may be a useful tool to help promote research on vascular aging., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Heffernan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Social isolation and lack of social support are risk factors for cardiovascular and cerebrovascular disease (CVD). This study explored the relationship between measures of social support and subclinical measures of CVD risk. 58 healthy adults ages 18 to 85 years participated in this study. The Berkman-Syme Social Network Inventory (SNI) was used to assess social isolation, with higher scores signifying less isolation. Social support was defined using the 12-Item Interpersonal Support Evaluation List (ISEL-12) with a higher score signifying higher social support. Subclinical CVD measures included carotid-femoral pulse wave velocity (cfPWV), carotid beta-stiffness index, and middle cerebral artery (MCA) pulsatility index. Path analysis models for both the SNI and ISEL appraisal domain predicting cfPWV and cerebrovascular pulsatility fit the data well. Path analyses showed significant direct paths from the SNI (β = -.363, t = -2.91) and ISEL appraisal domain (β = -.264, t = -2.05) to cfPWV. From cfPWV, both models revealed significant direct paths to carotid stiffness (β = .488, t = 4.18) to carotid pulse pressure (β = .311, t = 2.45) to MCA pulsatility (β = .527, t = 4.64). Social isolation and appraisal of social support are related to unfavorably higher aortic stiffness, with subsequent detrimental effects on cerebrovascular hemodynamic pulsatility.

Introduction: Age-related stiffening of the large elastic arteries (e.g., common carotid artery [CCA]) may impair wall dynamics (i.e., strain) and amplify transmission of pulsatile blood flow into the brain with large increases in pressure that occur during maximal resistance exercise (RE). The purpose of this study was to compare CCA arterial wall dynamics, central hemodynamics, and cerebral blood velocity responses during maximal RE between young and older adults., Methods: Thirty-one young (YA; 26 ± 5 yrs; 23.8 ± 3.3 kg/m 2 ) and 25 older adults (OA; 60 ± 6 yrs; 30.0 ± 5.5 kg/m 2 ) performed a unilateral maximal isokinetic knee flexion/extension exercise protocol (i.e., maximal RE). All measures were recorded at baseline and during the last 10 s of maximal RE. Common carotid artery strain, CCA strain time to peak, and CCA strain rate (i.e., variables of arterial wall dynamics) were analyzed using 2D speckle tracking software from circumferential ultrasound images. Transcranial Doppler was used to measure right middle cerebral artery (MCA) blood velocity. Non-invasive arterial blood pressure measurements were obtained using finger photoplethysmography., Results: Older adults had greater reductions in CCA strain time to peak from baseline to maximal RE (345 ± 39 to 242 ± 52 ms) than YA (308 ± 35 to 247 ± 42 ms; interaction effect, p < 0.01). MCA velocity was similar between YA and OA during maximal RE (p = 0.48), despite a greater arterial pressor response in OA (p < 0.01)., Conclusion: These data suggest cerebral blood velocity responds similarly during maximal RE among OA compared to YA, despite subtle age-related differences in the pressor and extracranial vascular response during maximal RE., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cerebral hemodynamics and pulsatility are important mechanisms of cerebrovascular and brain health. Cardiorespiratory fitness may improve cerebrovascular pulsatility in healthy females, but not in males. Whether cardiovascular disease (CVD) risk factors modify sex-specific associations of fitness with cerebral hemodynamics and vascular contributors to cerebral hemodynamics is unknown. We assessed V̇o 2peak and cerebrovascular hemodynamics in 157 adults without (42 ± 13 yr, BMI 24.5 ± 2.7 kg/m 2 ), and 66 adults with modifiable CVD risk factors (54 ± 8 yr, BMI 29.9 ± 4.0 kg/m 2 ). Intracranial [middle cerebral artery (MCA) pulsatility index (PI), mean velocity, conductance, and pulsatile damping] and extracranial hemodynamics [carotid artery wave transmission/reflection, PI, pulse wave velocity (PWV)-β, and carotid-femoral PWV] were assessed via transcranial Doppler/ultrasound and tonometry. Cardiorespiratory fitness was assessed via V̇o 2peak during an incremental exercise test. Multiple regression was used to assess contributions of V̇o 2peak to cerebrovascular outcomes after adjustment for relevant covariates. V̇o 2peak was inversely associated with MCA PI among females (β = -0.39, P = 0.01) but not males (β = -0.16, P = 0.25) without CVD risk factors. V̇o 2peak was positively associated with MCA PI among females (β = 0.44, P = 0.01) and not associated in males with CVD risk factors (β = -0.06, P = 0.079). V̇o 2peak was beneficially associated with vascular contributors to cerebral hemodynamics but had sex-specific associations with carotid stiffness and pulse pressure in females without CVD risk factors only. These results suggest that sex-specific associations between fitness and cerebral pulsatility among females without CVD risk factors may relate to the differential effects of fitness on carotid stiffness and pulse pressure. In addition, the presence of modifiable CVD risk factors may influence the protective relations of fitness on cerebrovascular hemodynamics. NEW & NOTEWORTHY We identify beneficial associations between cardiorespiratory fitness and lower carotid stiffness and pulse pressure as potential mechanisms underlying sex-specific associations of fitness and cerebral pulsatility in females without modifiable risk factors. Greater fitness is beneficially associated with conductance, pulsatile damping, and forward wave energy among adults without risk factors; however, associations are attenuated among adults with modifiable risk factors. These data suggest sex and risk factors may alter cerebrovascular sensitivity to cardiorespiratory fitness.

Age-related chronic diseases are among the most common causes of mortality and account for a majority of global disease burden. Preventative lifestyle behaviors, such as regular exercise, play a critical role in attenuating chronic disease burden. However, the exact mechanism behind exercise as a form of preventative medicine remains poorly defined. Interestingly, many of the physiological responses to exercise are comparable to aging. This paper explores an overarching hypothesis that exercise protects against aging/age-related chronic disease because the physiological stress of exercise mimics aging. Acute exercise transiently disrupts cardiovascular, musculoskeletal, and brain function and triggers a substantial inflammatory response in a manner that mimics aging/age-related chronic disease. Data indicate that select acute exercise responses may be similar in magnitude to changes seen with +10-50 years of aging. The initial insult of the age-mimicking effects of exercise induces beneficial adaptations that serve to attenuate disruption to successive "aging" stimuli (i.e., exercise). Ultimately, these exercise-induced adaptations reduce the subsequent physiological stress incurred from aging and protect against age-related chronic disease. To further examine this hypothesis, future work should more intricately describe the physiological signature of different types/intensities of acute exercise in order to better predict the subsequent adaptation and chronic disease prevention with exercise training in healthy and at-risk populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lefferts, Davis and Valentine.)

Background: The interactions between large artery function and neurovascular coupling (NVC) are emerging as important contributors to cognitive health. Women are disproportionally affected by Alzheimer's disease and related dementia later in life. Understanding large artery correlates of NVC in young women may help with preservation of cognitive health with advancing age., Purpose: To explore the association between large artery function, NVC and cognitive performance in young women., Methods: Vascular measurements were made in 61 women (21 ± 4 yrs) at rest and during a cognitive challenge (Stroop task). Transcranial Doppler was used to measure left middle cerebral artery (MCA) maximum velocity (V max ), mean velocity (V mean ), and pulsatility index (PI). NVC was determined as MCA blood velocity reactivity to the Stroop task. Large artery function was determined using carotid-femoral pulse wave velocity (cfPWV) as a proxy measure of aortic stiffness and carotid ultrasound-derived measures of compliance and reactivity (diameter change to the Stroop task). Cognitive function was assessed separately using a computerized neurocognitive battery that included appraisal of response speed, executive function, information processing efficiency, memory, attention/concentration, and impulsivity., Results: MCA V max reactivity was positively associated with executive function ( β = 0.26, 95% CI 0.01-0.10); MCA V mean reactivity was negatively associated with response speed ( β = -0.33, 95% CI -0.19 to -0.02) and positively with memory score ( β = 0.28, 95% CI 0.01-0.19). MCA PI reactivity was negatively associated with attention performance ( β = -0.29, 95% CI -14.9 to -1.0). Path analyses identified significant paths (p < 0.05) between carotid compliance and carotid diameter reactivity to select domains of cognitive function through MCA reactivity., Conclusions: NVC was associated with cognitive function in young women. Carotid artery function assessed as carotid compliance and carotid reactivity may contribute to optimal NVC in young women through increased blood flow delivery and reduced blood flow pulsatility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cilhoroz, DeBlois, Lefferts, Keller, Pagan Lassalle, Meyer, Stoner and Heffernan.)

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African-American, 42.10% Caucasian, body mass index (BMI) 20.1 ± 4.7 kg/m 2 ) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery β-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r = -0.27), and BMI (r = -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B = -1.3 [95%CI, -2.4, -0.2], β = -0.20, p < 0.05) after covariate adjustment for age, race, sex, pubertal stage, and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r = 0.45, p < 0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Introduction: There are well-established sex differences in central hemodynamic and cardiac adaptations to endurance exercise; however, controversial evidence suggests that excessive endurance exercise may be related to detrimental cardiovascular adaptations in marathoners., Purpose: To examine left ventricle (LV) structure, LV function, 24-h central hemodynamics and ventricular-vascular coupling in male and female marathoners and recreationally active adults., Methods: 52 marathoners (41 ± 5 years, n = 28 female, completed 6 ± 1 marathons/3 years) and 49 recreationally active controls (42 ± 5 years, n = 25 female) participated in the study. Three-Dimensional Echocardiography (3DE) was used to measure LV mass index and LV longitudinal (LS) circumferential (CS), area (AS), and radial strain (RS). An ambulatory blood pressure (BP) cuff was used to measure 24-h central hemodynamics (BP, pulse wave velocity, PWV, wave reflection index, RIx). Hemodynamic and 3DE measures were combined to derive the ratio of arterial elastance (Ea) to ventricular elastance (Elv) as a global measure of ventricular-vascular coupling., Results: There were no sex or group differences in LS, CS, AS, and RS (p > 0.05). Females marathoners had similar aortic BP (116 ± 9 vs. 113 ± 1 mmHg), and PWV (5.9 ± 0.5 vs. 5.9 ± 1.1 m/s) compared to female controls but lower aSBP (116 ± 9 vs. 131 ± 10 mmHg) and PWV (5.9 ± 0.5 vs. 6.2 ± 0.5 m/s) compared to male marathoners (p < 0.05). Female marathoners had lower Ea/Elv than female controls (0.67 ± 0.20 vs. 0.93 ± 0.36) and male marathoners (0.67 ± 0.20 vs. 0.85 ± 0.42, p < 0.05)., Conclusions: Women that have completed multiple marathons do not have reduced LV function or increased aortic stiffness and may have better ventricular-vascular coupling compared to male marathoners and their female untrained counterparts., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements., Objectives: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors., Methods: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression., Results: Compared with usual care, PST led to reductions in left amygdala activation (-0.75; 95% CI: -1.49, -0.01) and global scores of the negative affect circuit (-0.43; -0.81, -0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized β-coefficients were -0.67 in usual care and -0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and -2.02 in usual care and -0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized β-coefficients were -0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and -1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet., Conclusions: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Oxidative stress has been linked to reductions in vascular function during acute inflammation in young adults; however, the effect of acute inflammation on vascular function with aging is inconclusive. The aim of this study was to determine if oral antioxidant administration eliminates vascular dysfunction during acute inflammation in young and older adults. Brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV) were measured in nine young (3 male, 24 ± 4 yrs, 26.2 ± 4.9 kg/m 2 ) and 16 older (13 male, 64 ± 5 yrs, 25.8 ± 3.2 kg/m 2 ) adults before and 2-h after oral consumption of 2 g of vitamin C. The vitamin C protocol was completed at rest and 24 h after acute inflammation was induced via the typhoid vaccine. Venous blood samples were taken to measure markers of inflammation and vitamin C. Both interleukin-6 (Δ+0.7 ± 1.8 pg/ml) and C-reactive protein (Δ+1.9 ± 3.1 mg/L) were increased at 24 h following the vaccine (p < 0.01). There was no change in FMD or PWV following vitamin C administration at rest (p > 0.05). FMD was lower in all groups during acute inflammation (Δ-1.4 ± 1.9%, p < 0.01), with no changes in PWV (Δ-0.0 ± 0.9 m/s, p > 0.05). Vitamin C restored FMD back to initial values in young and older adults during acute inflammation (Δ+1.0 ± 1.8%, p < 0.01) with no change in inflammatory markers or PWV (p > 0.05). In conclusion, oral vitamin C restored endothelial function during acute inflammation in young and older adults, with no effect on aortic stiffness. The effect of vitamin C on endothelial function did not appear to be due to reductions in inflammatory markers. The exact mechanisms should be further investigated., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

New Findings: What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness., Abstract: Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7 years old; 11 female) and 15 sex-matched young adults (25 ± 4 years old) at rest and during the CP test (4 min, 6.4 ± 0.8°C) and LBNP (6 min, -20 mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P < 0.05). Pulsatile damping decreased in both groups (P < 0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P < 0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P < 0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness., (© 2021 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined., Methods: Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task., Results: Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes ( P < .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions ( P < .05). There were no condition × time interactions for cognitive performance., Conclusions: Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS., Competing Interests: Financial Disclosures: The authors declare no conflicts of interest., (© 2021 Consortium of Multiple Sclerosis Centers.)

Purpose: Aortic stiffness may affect shear patterns in the peripheral vasculature. This study examined if sprint exercise, which typically increases aortic stiffness is associated with increased peripheral retrograde blood flow and impaired microvascular function., Methods: Twenty participants (10 women; age: 27 ± 5 years) underwent arterial stiffness, shear rate, and microvascular function assessment at three time points: baseline; following time control; ~ 2 min post a 30-s cycle ergometer sprint against 7.0% body mass. Aortic stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV). Superficial femoral artery (SFA) diameter and blood velocity were assessed using Doppler-ultrasound and were used to calculate shear rates and resistance index (RI). SFA wave reflections were obtained via wave intensity analysis. Vastus medialis microvascular function was measured as tissue saturation index reactivity pre-post exercise via near-infrared spectroscopy., Results: cfPWV increased by + 0.8 ± 0.7 m·s -1 following exercise (p < 0.001). Retrograde shear was reduced following exercise compared with time control (- 4.9 ± 3.8 s -1 ; p < 0.001), while tissue saturation index was increased post-exercise from baseline (+ 2.3 ± 4.6%; p = 0.04). Reductions in SFA wave reflections (- 1.70 ± 1.96 aU) and RI (- 0.17 ± 0.13 aU) were also noted following exercise (p < 0.001)., Conclusion: These data suggest sprint exercise-mediated changes in peripheral shear patterns and microvascular function in the exercised vasculature occur independent from increases in aortic stiffness. Exercise-induced reductions in SFA retrograde shear may be related to decreased wave reflections and peripheral vascular resistance.

Cerebral pulsatility reflects a balance between the transmission and damping of pulsatility in the cerebrovasculature. Females experience greater cerebral pulsatility with aging, which may have implications for sex differences in stroke risk and cognitive decline. This study sought to explore vascular contributors to cerebral pulsatility and pulsatile damping in men and women. Adults ( n = 282, 53% female) underwent measurements of cerebral (middle cerebral artery) pulsatility, pulsatile damping (ratio of cerebral to carotid pulsatility), large artery stiffening (ratio of aortic to carotid pulse wave velocity), and carotid wave transmission/reflection dynamics using wave intensity analysis. Multiple regression revealed that older age, female sex, greater large artery stiffening, higher carotid pulse pressure, and greater forward wave energy was associated with increased cerebral pulsatility (adjusted R 2  = 0.44, P < 0.05). Contributors to decreased cerebral pulsatile damping included older age, female sex, and lower wave reflection index (adjusted R 2  = 0.51, P < 0.05). Our data link greater large artery stiffening, carotid pulse pressure, and forward wave energy to greater cerebral pulsatility, while greater carotid wave reflection may enhance cerebral pulsatile damping. Lower cerebral pulsatile damping among females may contribute to greater age-associated cerebral pulsatile burden compared with males. NEW & NOTEWORTHY Cerebral pulsatility contributes to brain health and depends on a balance between transmission and damping of pulsatile hemodynamics into the cerebrovasculature. Our data indicate that cerebral pulsatility increases with age, female sex, extracranial artery stiffening, forward wave energy, and pulse pressure, whereas pulsatile damping decreases with age and female sex and increases with greater carotid wave reflections. These novel data identify pulsatile damping as a potential contributor to sex differences in cerebral pulsatile burden.

ANCHORS A-WHEY was a 12-week randomized controlled trial (RCT) designed to examine the effect of whey protein on large artery stiffness, cerebrovascular responses to cognitive activity and cognitive function in older adults., Methods: 99 older adults (mean ± SD; age 67 ± 6 years, BMI 27.2 ± 4.7kg/m 2 , 45% female) were randomly assigned to 50g/daily of whey protein isolate (WPI) or an iso-caloric carbohydrate (CHO) control for 12 weeks (NCT01956994). Aortic stiffness was determined as carotid-femoral pulse wave velocity (cfPWV). Aortic hemodynamic load was assessed as the product of aortic systolic blood pressure and heart rate (Ao SBP × HR). Cerebrovascular response to cognitive activity was assessed as change in middle-cerebral artery (MCA) blood velocity pulsatility index (PI) during a cognitive perturbation (Stroop task). Cognitive function was assessed using a computerized neurocognitive battery., Results: cfPWV increased slightly in CHO and significantly decreased in WPI ( p < 0.05). Ao SBP × HR was unaltered in CHO but decreased significantly in WPI ( p < 0.05). Although emotion recognition selectively improved with WPI ( p < 0.05), WPI had no effect on other domains of cognitive function or MCA PI response to cognitive activity ( p > 0.05 for all)., Conclusions: Compared to CHO, WPI supplementation results in favorable reductions in aortic stiffness and aortic hemodynamic load with limited effects on cognitive function and cerebrovascular function in community-dwelling older adults.

The burden of heart failure is disproportionately higher in African Americans, with a higher prevalence seen at an early age. Examination of racial differences in left ventricular mass (LVM) in childhood may offer insight into risk for cardiac target organ damage (cTOD) in adulthood. Central hemodynamic load, a harbinger of cTOD in adults, is higher in African Americans. The purpose of this study was to examine racial differences in central hemodynamic load and LVM in African American and non-Hispanic white (NHW) children. Two hundred sixty-nine children participated in this study (age, 10 ± 1 years; n = 149 female, n = 154 African American). Carotid pulse wave velocity (PWV), forward wave intensity (W1) and reflected wave intensity (negative area, NA) was assessed from simultaneously acquired distension and flow velocity waveforms using wave intensity analysis (WIA). Wave reflection magnitude was calculated as NA/W1. LVM was assessed using standard 2D echocardiography and indexed to height as LVM/[height (2.16) + 0.09]. A cutoff of 45 g/m (2.16) was used to define left ventricular hypertrophy (LVH). LVM was higher in African American vs. NHW children (39.2 ± 8.0 vs. 37.2 ± 6.7 g/m (2.16), adjusted for age, sex, carotid systolic pressure and socioeconomic status; p < 0.05). The proportion of LVH was higher in African American vs. NHW children (25 vs. 12 %, p < 0.05). African American and NHW children did not differ in carotid PWV (3.5 ± 4.9 vs. 3.3 ± 1.3 m/s; p > 0.05). NA/W1 was higher in African American vs. NHW children (8.5 ± 5.3 vs. 6.7 ± 2.9; p < 0.05). Adjusting for NA/W1 attenuated racial differences in LVM (38.8 ± 8.0 vs. 37.6 ± 7.0 g/m (2.16); p = 0.19). In conclusion, racial differences in central hemodynamic load and cTOD are present in childhood. African American children have greater wave intensity from reflected waves and higher LVMI compared to NHW children. WIA offers novel insight into early life origins of racial differences in central hemodynamic load and cTOD., (Copyright © 2020 Heffernan, Lefferts, Atallah-Yunes, Glasgow and Gump.)

Background: High altitude sojourn challenges blood flow regulation in the brain, which may contribute to cognitive dysfunction. Neurovascular coupling (NVC) describes the ability to increase blood flow to working regions of the brain. Effects of high altitude on NVC in frontal regions undergoing cognitive activation are unclear but may be relevant to executive function in high-altitude hypoxia. This study sought to examine the effect of incremental ascent to very high altitude on NVC by measuring anterior cerebral artery (ACA) and middle cerebral artery (MCA) hemodynamic responses to sustained cognitive activity. Materials and Methods: Eight adults (23 ± 7 years, four female) underwent bilateral measurement of ACA and MCA mean velocity and pulsatility index (PI) through transcranial Doppler during a 3-minute Stroop task at 1400, 3440, and 4240 m. Results: Resting MCA and ACA PI decreased with high-altitude hypoxia ( p  < 0.05). Cognitive activity at all altitudes resulted in similar increases in MCA and ACA mean velocity, and decreases in ACA and MCA PI ( p  < 0.05 for MCA, p  = 0.07 for ACA). No significant altitude-by-Stroop interactions were detected, indicating NVC was stable with increasing altitude. Conclusions: Ascent to very high altitude (4240 m) using an incremental profile that supports partial acclimatization does not appear to disturb (1) increases in cerebral blood velocity and (2) reductions in pulsatility that characterize optimal NVC in frontal regions of the brain during cognitive activity.

Sex differences exist in vascular responses to blood pressure perturbations, such as resistance exercise. Increases in aortic stiffness following acute resistance exercise appear different between sexes, with attenuated increases in females vs. males. Whether sex differences exist in carotid stiffness, following resistance exercise is unknown. This study sought to examine sex differences in carotid stiffness, aortic stiffness, and hemodynamics following acute resistance exercise. Thirty-five participants (18 male) completed 3 sets of 10 repetitions of maximal isokinetic knee extension/flexion. Aortic stiffness and hemodynamics were estimated using an automated oscillometric blood pressure monitor at baseline, 5- and 30-min post-exercise. Carotid stiffness was assessed by β-stiffness index, pressure-strain elastic modulus and arterial compliance using ultrasonography. Resistance exercise increased aortic stiffness, mean and systolic pressure at 5-min (p<0.01), and pressure-strain elastic modulus at 5-min in both sexes (p<0.05). Arterial compliance decreased at 5- and 30-min post exercise in both sexes (p<0.01). No interaction effects were detected in carotid stiffness, aortic stiffness, and hemodynamics, indicating similar vascular responses between sexes. Our findings indicate that the large arteries appear to stiffen similarly following resistance exercise in males and females when presented with similar blood pressure responses., Competing Interests: The authors declare no conflict of interest, (© Georg Thieme Verlag KG Stuttgart · New York.)

Acute inflammation is associated with increased risk of cardiovascular events and impaired vasodilatory capacity. Vasodilatory capacity can be measured in different segments of the arterial tree; however, it is unknown if the effects of acute inflammation are vascular segment-specific or if inflammation-induced dysfunction can be attenuated by factors that modulate cardiovascular risk, such as high cardiorespiratory fitness. The purpose of this study was to determine the effect of acute inflammation and fitness on conduit artery, resistance artery, and microvascular function in healthy, young adults. Vascular function was assessed at baseline and 24 h after a typhoid vaccination in 11 low-fit (5 male, 24 yr of age, 34.5 ± 2.9 ml·kg -1 ·min -1 peak O 2 uptake (V̇o 2peak )] and 12 high-fit (7 male, 27 yr of age, 56.4 ± 9.7 ml·kg -1 ·min -1 V̇o 2peak ) young adults. Vascular assessments included flow-mediated dilation (FMD) of the brachial artery, forearm reactive hyperemia (RH) via venous occlusion plethysmography, and near-infrared spectroscopy (NIRS) during a 5-min arterial occlusion. Acute inflammation was evident with increases in IL-6 and C-reactive protein ( P < 0.01), and mean arterial pressure did not change ( P = 0.33). FMD was lower in the high-fit group, yet it was reduced in both groups at 24 h, even after controlling for shear ( P < 0.05). No effect of acute inflammation was observed for RH or NIRS ( P > 0.05). Acute inflammation had nonuniform effects on vascular function throughout the arterial tree in young adults, and fitness did not alter the vascular response. This suggests that cardiorespiratory fitness may not protect the vasculature during acute inflammation in young adults in the absence of age- or disease-related decline in vascular function.

Introduction: Retrograde shear causes endothelial damage and is pro-atherogenic. The purpose of our study was to examine the impact of vascular remodeling from habitual exercise training on acute changes in retrograde shear and microvascular oxygenation (SMO 2 ) induced via 30 min of external compression., Methods: Participants included 11 exercise trained (ET) men (Division I track athletes; age 20 ± 3 years) and 18 recreationally active (RA) men (age 23 ± 5 years). Near-infrared spectroscopy (NIRS) was used to measure vastus medialis SMO 2 . Doppler-ultrasound was used to assess SFA intima-media thickness, diameter and flow velocity to derive retrograde shear. Vascular measures were made at baseline (BASELINE), during a sham condition (calf compression to 5 mmHg, SHAM) and during the experimental condition (calf compression to 60 mmHg, EXP)., Results: Compared to RA, ET had larger SFA diameters (0.66 ± 0.06 vs 0.58 ± 0.06 cm, p < 0.05) and lower SFA IMT (0.33 ± 0.03 vs 0.36 ± 0.07 mm, p < 0.05). Retrograde shear increased similarly in both groups during EXP (p < 0.05) but ET men had lower overall retrograde shear during the conditions (BASELINE 75.8 ± 26.8 vs EXP 88.2 ± 16.9 s -1 ) compared to RA men (BASELINE 84.4 ± 23.3 vs EXP 106.4 ± 19.6 s -1 p < 0.05). There was a similar increase in SMO 2 from BASELINE to SHAM (ET + 8.1 ± 4.8 vs RA + 6.4 ± 9.7%) and BASELINE to EXP (ET + 8.7 ± 6.4 vs RA + 7.1 ± 9.0%) in both groups., Conclusion: Beneficial vascular remodeling in ET men is associated with lower retrograde shear during external compression. Acute increases in retrograde shear with external compression do not detrimentally impact microvascular oxygenation.

Acute inflammation increases the risk of cardiac and cerebrovascular events, possibly related to alterations in the hemodynamic load. Wave reflection at the aorta and carotid provides insight into downstream vascular changes and hemodynamic load at the heart and brain. Acute inflammation has been suggested to reduce wave reflection via downstream vasodilation; however, this is not firmly established and has only been investigated at the aorta. We sought to explore the effect of acute inflammation on aortic and carotid hemodynamics in healthy, young adults. Pressure waveforms were collected via radial and carotid applanation tonometry in 23 adults (26 ± 4 years) before and 24 h after a typhoid vaccination. Waveforms were calibrated to brachial mean and diastolic pressure, and waveform separation analyses (WSA) were performed, yielding augmentation index, reflection index, time to reflection (Tr), forward (Pf) and reflected (Pb) wave magnitude, and pulse wave velocity. Arterial diameters and carotid stiffness were measured via ultrasonography. Acute inflammation reduced wave reflection at 24 h in both the aorta and carotid (P < 0.05) without changes in mean pressure. WSA did not reveal independent changes in Pf, Pb, or Tr (P > 0.05). Arterial stiffness did not change; however, brachial and carotid artery diameters increased. Acute inflammation reduces wave reflection in the aorta and carotid artery in young adults, potentially due to downstream/peripheral vasodilation. Reduced aortic wave reflection did not disturb the cardiac workload; however, reductions in carotid wave reflection may render the brain vulnerable to pulsatile hemodynamics. These findings may have implications for cardiac and cerebrovascular risk during acute inflammation., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

High altitude sojourn is broadly associated with impaired cognitive function, although there are inconsistencies within the literature. Incorporation of mathematical modeling to gain insight into latent aspects of decision-making may strengthen the ability to characterize changes in cognitive function during high altitude sojourn. This study sought to examine the effects of high altitude on cognitive function and underlying constructs of decision-making during an 11-d incremental ascent to 5160 m in 18 healthy adults (26 ± 12 yrs). Participants underwent cognitive testing at 116 m, 3440 m, 4240 m, and 5160 m. Cognitive function was assessed using standard metrics of accuracy and reaction time (RT) during working memory (2-back) and attention (Flanker) tasks. Behavioral data were additionally analyzed using drift-diffusion modeling to interrogate latent neural (strength of evidence, non-decision time) and behavioral (caution, bias) processes of decision-making. Flanker accuracy was unaltered during incremental ascent to high altitude, while 2-back accuracy decreased at 5160 m (p < 0.01). RT was faster at 4240 m for the Flanker, and faster at all altitudes compared to 116 m for the 2-back (p < 0.01). Incremental ascent to high altitude elicited modest reductions in caution and non-decision time, increases in bias and strength of evidence for non-match items during the 2-back (0.04 ≥ p > 0.01). These data indicate that while RT may appear to improve during incremental ascent to high altitude, increases in speed may be driven by participants 1) accumulating less evidence before initiating a response (i.e., less cautious) and 2) preferentially attending to (more biased), and extracting more evidence from, frequent/easier stimuli, rather than improved processing per se. Taken together, changes in cognitive function during incremental ascent to high altitude may reflect subtle changes in neural and behavioral components of decision-making intended to reduce cognitive load and conserve brain resources under challenging environmental conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hypertension accelerates brain aging, resulting in cognitive dysfunction with advancing age. Exercise is widely recommended for adults with hypertension to attenuate cognitive dysfunction. Whether acute exercise benefits cognitive function in this at-risk population is unknown. The purpose of this study was to compare the effects of acute aerobic exercise on cognitive function in 30 middle-aged hypertensive (HTN) and 30 age, sex, and body mass index (BMI)-matched non-HTN adults (56 ± 6 years, BMI 28.2 ± 2.9 kg/m 2 ; 32 men). Subjects underwent cognitive testing pre/post 30-min cycling (≈55% peak oxygen consumption). Cognition was assessed using standard metrics of accuracy and reaction time (RT) across memory recognition, 2-back, and Flanker tasks. Behavioral data was further analyzed using drift-diffusion modeling to examine underlying components of decision-making (strength of evidence, caution, bias) and RT (non-decision time). Exercise elicited similar changes in cognitive function in both HTN and non-HTN groups ( p > 0.05). Accuracy was unaltered for Flanker and 2-back tasks, while hits and false alarms increased for memory recognition post-exercise ( p < 0.05). Modeling results indicated changes in memory hits/false alarms were due to significant changes in stimulus bias post-exercise. RT decreased for Flanker and memory recognition tasks and was driven by reductions in post-exercise non-decision time ( p < 0.05). Our data indicate acute exercise resulted in similar, beneficial cognitive responses in both middle-age HTN and non-HTN adults, marked by unaltered task accuracy, and accelerated RT post-exercise. Additionally, drift-diffusion modeling revealed that beneficial acceleration of cognitive processing post-exercise (RT) is driven by changes in non-decision components (encoding/motor response) rather than the decision-making process itself.

Hypertension, even when controlled, may accelerate arterial stiffening and impair the ability of the cerebrovasculature to increase blood flow to support neural activity, i.e., neurovascular coupling (NVC). Optimal NVC depends on continuous, nonpulsatile flow, which is partially determined by extra- and intracranial vessel function. We sought to compare extra- and intracranial hemodynamics during cognitive activity (Stroop task) in 30 middle-aged, well-controlled medicated hypertensive and 30 age-, sex-, and body mass index (BMI)-matched nonhypertensive adults (56 ± 6 years, 28.2 ± 2.9 kg/m 2 BMI; 32 men). Aortic and carotid (single point) pulse wave velocity (PWV) were assessed via tonometry and ultrasound, respectively. Carotid and middle cerebral artery (MCA) blood velocity pulsatility were measured via ultrasound and Doppler. Prefrontal cortex (PFC) oxygenation was measured via tissue saturation index (TSI) using near-infrared spectroscopy. Accuracy and reaction times were computed to assess cognitive performance. Stroop performance was similar between groups ( P > 0.01). Aortic and carotid PWV increased, carotid flow pulsatility decreased ( P < 0.01), and MCA flow pulsatility and PFC TSI were maintained during Stroop ( P > 0.01). Our findings indicate that middle-age adults with medically controlled hypertension and adults without hypertension demonstrate similar intra- and extracranial cerebrovascular reactivity during cognitive engagement. Despite increases in large artery stiffness, middle-aged adults with controlled hypertension and without hypertension exhibit reductions in extracranial flow pulsatility during cognitive engagement that may be part of a concerted cerebrovascular response to support downstream cerebral oxygenation and overall NVC. NEW & NOTEWORTHY Hypertension is associated with accelerated arterial stiffening, which may alter extra- and intracranial vascular reactivity during cognitive activity and impair neurovascular coupling. Middle-aged adults with medicated hypertension exhibit similar neurovascular coupling and extra-/intracranial vascular reactivity during sustained cognitive activity. Extracranial modulation of central hemodynamics may be an important component of optimal neurovascular coupling.

Introduction: While resistance exercise (RE) is known to be beneficial for overall health, one bout of RE acutely increases aortic stiffness and pulse pressure (PP). Increases in aortic stiffness and PP in a setting of aging has been shown to detrimentally impact cognitive function. This study examined whether increased aortic stiffness and PP from an acute bout of RE is associated with cognitive function., Methods: Thirty-five participants (21 ± 2 years) underwent cognitive testing before and after either an acute bout of RE or a non-exercise time-control condition. Cognitive function was assessed as reaction time and accuracy during memory recognition, attention (Flanker) and working memory (N-back) tasks. Aortic stiffness and PP were measured via pulse wave velocity (PWV) and pulse wave analysis, respectively, using a brachial oscillometric device., Results: There were significant increases in aortic PWV and aortic PP following RE (p < 0.05) with no change in PWV or PP following the non-exercise control condition (p > 0.05). There was no change in accuracy metrics (% hits) across conditions for any cognitive task (p > 0.05). There was a condition-by-time interaction for reaction time for the memory task (p < 0.05) driven by a significant decrease in reaction times following RE (p < 0.05) with no change in reaction time following the non-exercise control (p > 0.05)., Conclusion: Functional increases in aortic stiffness and pulse pressure following acute RE occur in the absence of detrimental changes in cognitive function in young, healthy adults.

Objectives: Stiffer central arteries, as seen in hypertension (HTN), foster transmission of pulsatile hemodynamics into fragile cerebral vessels. Aerobic exercise is recommended for adults with HTN, but its effects on arterial stiffness and pulsatility in this group are unclear. This study sought to investigate the effect of acute aerobic exercise on arterial stiffness and cerebrovascular pulsatility in 30 adults with treated HTN and 30 age, sex, and BMI-matched adults without HTN (56 ± 6 years, BMI 28.2 ± 2.9 kg/m; 28 women)., Methods: Patients underwent hemodynamic measures before/after 30-min cycling (≈55% peak oxygen consumption). Aortic stiffness was measured using carotid-femoral pulse wave velocity, and carotid artery stiffness was assessed with β-stiffness via ultrasound. Aortic/carotid pulse pressure (aortic via radial generalized transfer function) was measured by tonometry and calibrated to brachial mean pressure and diastolic pressure. Carotid/middle cerebral artery (MCA) blood velocity pulsatility indices were measured using Doppler. Carotid wave intensity analysis was used to derive forward wave intensity (W1)., Results: Exercise impacted hemodynamics similarly in HTN compared to no-HTN. Carotid-femoral pulse wave velocity, MCA pulsatility index, carotid pulsatility index, and W1 increased similarly after exercise in both groups (P < 0.05). Carotid pulse pressure and β-stiffness were unaltered after exercise. Postexercise changes in W1 were positively associated with carotid pulsatility index, which was further associated with MCA pulsatility index., Conclusions: These data suggest adults with treated HTN experience similar increases in aortic stiffness and cerebrovascular hemodynamic pulsatility during early recovery from acute aerobic exercise as their counterparts without HTN.

This study examined central artery stiffness and hemodynamic pulsatility during cognitive engagement in younger and older adults., Methods: Vascular-hemodynamic measures were completed in 19 younger (age 35±1yrs) and 20 older (age 69±2yrs) adults at rest and during a Stroop task. Aortic stiffness (carotid-femoral pulse wave velocity, PWV) and carotid pulse pressure (PP) were assessed using applanation tonometry. Carotid stiffness was assessed as a single-point PWV using Doppler Ultrasound. Middle cerebral artery (MCA) mean flow and flow pulsatility index (PI) were assessed using transcranial Doppler. Cognitive function was assessed as accuracy and reaction time from the Stroop task., Results: Older adults had lower accuracy scores and longer reaction times on the Stroop task compared to younger adults (p<0.05). Both age groups had similar increases in MCA mean flow during Stroop (p<0.05). There were significant increases in aortic PWV, carotid PWV, carotid PP and MCA PI during Stroop in older but not younger adults (p<0.05). Carotid PP and MCA PI assessed during Stroop were statistical mediators of the association between age group and Stroop performance metrics (accuracy and reaction time, p<0.05), while aortic and carotid PWV were indirect statistical mediators of MCA PI through carotid PP (p<0.05)., Conclusions: Older adults experience increases in large artery stiffness during cognitive engagement possibly preventing effective buffering of pulsatile hemodynamic energy entry into the cerebrovasculature. This is important as pulsatile flow during cognitive engagement, and not mean flow per se, was related to overall cognitive performance., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Acute resistance exercise has been shown to reduce brachial endothelial function. Whether there are concomitant reductions in carotid endothelial function remains unexplored., Methods: Cold pressor test-mediated vasodilation of the carotid artery was used to assess carotid endothelial function in 15 young and healthy participants (age 26 ± 1 years, body mass index 24 ± 1 kg/m 2 ) after acute resistance exercise or an inactive time control condition., Results: Acute resistance exercise had no effect on the cold pressor test-mediated vasodilation compared to time control (5.8 ± 0.8 vs 6.2 ± 0.9% dilation, p > 0.05)., Interpretation: Carotid endothelial function may not be compromised following acute resistance exercise in young healthy adults.

Background and Aims: Carotid extra-media thickness (EMT) encompasses arterial adventitia and perivascular adipose tissue (PAT). Adventitial remodeling and PAT may contribute independently to functional (stiffness) and structural (remodeling) changes in artery wall properties. Visceral adiposity may contribute to PAT, thereby affecting artery stiffness. We investigated the relationships between carotid artery stiffness, EMT, and visceral adiposity in young, healthy individuals., Methods: 135 healthy males (20 ± 2 yr, body mass index [BMI] 24.8 ± 3.3 kg/m 2 ) underwent anthropometric and vascular measures on two separate days. Visceral adiposity was assessed using waist circumference and sagittal abdominal diameter (SAD). Brachial and carotid systolic, diastolic, and pulsatile (PP) blood pressures were assessed using an oscillometric cuff and applanation tonometry, respectively. Carotid intima-media thickness (IMT) and EMT were assessed using Doppler ultrasound. Carotid artery stiffness was calculated as β-stiffness and calibrated to carotid pressures., Results: Separate stepwise multiple regression models demonstrated that carotid PP (β = 0.205) and EMT (β = 0.267) accounted for 12.6% of variance in β-stiffness, while carotid PP (β = 0.195) and SAD (β = 0.226) accounted for 10.5% of variance in EMT (p < 0.05). Mediation analyses revealed carotid PP partially mediated the relationship between a) EMT and β-stiffness, and b) SAD and EMT (p < 0.05)., Conclusions: Carotid PP and EMT, but not IMT, are related to carotid β-stiffness. Carotid PP and visceral adiposity (SAD) are related to EMT. Carotid PP partially mediates the association between a) EMT and carotid β-stiffness, and b) SAD and EMT. Our findings suggest visceral adiposity may detrimentally affect subclinical markers of cardiovascular disease risk (carotid PP, EMT) and contribute to artery stiffness., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Left ventricular (LV) structure and function are predictors of cardiovascular (CV) morbidity and mortality and are related to resting peripheral haemodynamic load in older adults. The central haemodynamic response to exercise may reveal associations with LV structure and function not detected by traditional peripheral (brachial) measures in a younger population., Purpose: To examine correlations between acute exercise-induced changes in central artery stiffness and wave reflections and measures of resting LV structure and function., Methods: Sixteen healthy men (age 26 ± 6 year; BMI 25·3 ± 2·7 kg m -2 ) had measures of central haemodynamic load measured before/after a 30-s Wingate anaerobic test (WAT). Common carotid artery stiffness and reflected wave intensity were assessed via wave intensity analysis as a regional pulse wave velocity (PWV) and negative area (NA), respectively. Resting LV structure (LV mass) and function [midwall fractional shortening (mFS)] were assessed using M-mode echocardiography in the parasternal short-axis view., Results: There was a significant association between mFS and WAT-mediated change in carotid systolic BP (r = -0·57, P = 0·011), logNA (r = -0·58, P = 0·009) and PWV (r = -0·44, P = 0·045). There were no significant associations between resting mFS and changes in brachial systolic BP (r = -0·26, P>0·05). There were no associations between resting LV mass and changes in any haemodynamic variable (P>0·05)., Conclusion: Exercise-induced increases in central haemodynamic load reveal associations with lower resting LV function in young healthy men undetected by traditional peripheral haemodynamics., (© 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Objective: To investigate racial differences in central blood pressure and vascular structure/function as subclinical markers of atherosclerotic cardiovascular disease in children., Study Design: This cross-sectional study recruited 54 African American children (18 female, 36 male; age 10.5 ± 0.9 years) and 54 white children (27 female, 26 male; age 10.8 ± 0.9 years) from the Syracuse City community as part of the Environmental Exposures and Child Health Outcomes study. Participants underwent blood lipid and vascular testing on 2 separate days. Carotid artery intima-media thickness and aortic stiffness were measured by ultrasonography and carotid-femoral pulse wave velocity, respectively. Blood pressure was assessed at the brachial artery and estimated in the carotid artery using applanation tonometry., Results: African American children had significantly higher pulse wave velocity (4.8 ± 0.8 m/s) compared with white children (4.2 ± 0.7 m/s; P < .05), which remained significant after adjustment for confounding variables including socioeconomic status. African American children had significantly higher intima-media thickness (African American 0.41 ± 0.06, white 0.39 ± 0.05 mm), and carotid systolic blood pressure (African American 106 ± 11, white 102 ± 8 mm Hg; P < .05) compared with white children, although these racial differences were no longer present after covariate adjustments for height., Conclusions: Racial differences in aortic stiffness are present in childhood. Our findings suggest that racial differences in subclinical cardiovascular disease occur earlier than previously recognized., (Copyright © 2016 Elsevier Inc. All rights reserved.)

New Findings: What is the central question of this study? Although heat stress is known to increase cardiovascular strain, no study, to date, had explored the potential impact of exercise-induced heat stress on vascular function. What is the main finding and its importance? We found that acute exercise tended to reduce flow-mediated dilatation (FMD), owing in part to reduced reactive hyperaemia/shear stimulus; thus, when FMD is normalized to shear no postexercise deficit exists. Exercise-induced heat stress increased reactive hyperaemia, shear rate, coupled with a sustained FMD postexercise, suggests that exercise-induced heat stress increases the amount of shear stimulus to elicit a similar response, indicating reduced vascular responsiveness, or reserve, which might increase cardiovascular susceptibility. Heat stress increases cardiovascular strain and is of particular concern in occupations, such as firefighting, in which individuals are required to perform strenuous work while wearing personal protective equipment. Sudden cardiac events are associated with strenuous activity and are the leading cause of duty-related death among firefighters, accounting for ∼50% of duty-related fatalities per year. Understanding the acute effects of exercise-induced heat stress (EIHS) on vascular endothelial function may provide insight into the mechanisms precipitating acute coronary events in firefighters. The purpose of this study, therefore, was to determine the effects of EIHS on vascular endothelial function. Using a balanced crossover design, 12 healthy men performed 100 min of moderate-intensity, intermittent exercise with and without EIHS (personal protective equipment or cooling vest, respectively). Measurements of flow-mediated dilatation (FMD), reactive hyperaemia and shear rate area under the curve (SR AUC ) were performed pre- and postexercise. During EIHS, core temperature was significantly higher (38 ± 0.1 versus 37 ± 0.1°C). Postexercise FMD tended to be suppressed in both conditions, but was not different from pre-exercise. Reactive hyperaemia was reduced after no-EIHS but increased after EIHS. Thus, normalizing FMD to the shear stimulus (FMD/SR AUC ) revealed a significant reduction in FMD after EIHS only (pre-exercise 0.15 ± 0.04 and 0.13 ± 0.02 s -1 versus postexercise, 0.13 ± 0.02 and 0.06 ± 0.02 s -1 , no-EIHS and EIHS, respectively). We conclude that moderate heat stress superimposed on moderate-intensity exercise resulted in reduced vascular endothelial function. This heat stress-induced alteration in the shear-dilatory relationship may relate to the increased risk of acute coronary events associated with activities that combine physical exertion and heat stress (i.e. firefighting)., (© 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.)

Background: High blood pressure (BP) may be associated with impaired cognitive function. BP is comprised of a steady (mean arterial pressure; MAP) and pulsatile (pulse pressure; PP) component. The purpose of this study was to examine the relationship between steady and pulsatile BP and cognition among adults ≥60years old., Methods: 2058 adults age 60-85years from the 1999-2002 NHANES were used in this analysis. MAP and PP were calculated from brachial BP as 1/3 systolic +2/3 diastolic BP, and systolic - diastolic BP, respectively. Cognition was assessed using the digit-symbol substitution test (DSST)., Results: Unadjusted multiple regression revealed although PP independently predicted DSST score (β=-0.21, p<0.05), MAP was only predictive when entered simultaneously with PP (β=0.06, p<0.05). Further adjustments for sociodemographics and medical history significantly improved prediction of DSST score (∆R 2 =0.37, p<0.05), and removed the association between MAP and DSST score, although PP remained a significant predictor (β=-0.07, p<0.05)., Conclusions: PP, but not MAP, was significantly and inversely related to cognitive function among a representative sample of adults aged ≥60years after controlling for sociodemographic information and medical history., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Exercise in hypoxia places added demands on the brain and cerebrovasculature that can impact cognitive function. The purpose of this study was to investigate the effect of acute hypoxia on cerebrovascular hemodynamics, markers of neuro-steroidal modulation and brain-blood barrier (BBB) integrity, and cognition during exercise. Thirty healthy participants (21±4yrs., BMI 24.0±2.6kg∙m(-2); 15 men) were randomized to both a≈2.5h normoxic (FiO2 20.0%) and hypoxic (FiO2 12.5%) condition on two separate days. After 1.25h, participants underwent 10min of exercise-alone (cycling at 55% HRmax) and 15min of exercise+cognitive testing. Prefrontal cortex (PFC) tissue oxygenation and middle cerebral artery (MCA) mean blood velocity (MnV) were measured using near-infrared spectroscopy and transcranial Doppler respectively at rest, during exercise-alone, and during exercise+cognitive testing. Salivary levels of dehydroepiandosterone [DHEA], DHEA-sulfate [DHEAS]) and neuron specific enolase (NSE) were measured pre and post exercise. Cognition was assessed using standard metrics of accuracy and reaction time (RT), and advanced metrics from drift-diffusion modeling across memory recognition, N-Back and Flanker tasks. MCA MnV increased from rest to exercise (p<0.01) and was unchanged with addition of cognitive testing during exercise in both normoxia and hypoxia. PFC oxygenation increased during exercise (p<0.05) and was further increased with addition of cognitive challenge in normoxia but decreased during exercise in hypoxia (p<0.05) with further reductions occurring with addition of cognitive tasks (p<0.05). DHEA and NSE increased and decreased post-exercise, respectively, in both normoxia and hypoxia (p<0.01). Accuracy on cognitive tasks was similar in normoxia compared to hypoxia, while RT was slower in hypoxia vs normoxia across memory recognition (p<0.01) and Flanker tasks (p=0.04). Drift-diffusion modeling suggested changes in memory RT were due to increases in caution (p<0.01). Overall cognitive performance is maintained during exercise in hypoxia concomitant with slower RT in select cognitive tasks and reduced oxygenation in the PFC. These changes were accompanied by slight increases in neuro-steroidal modulation but appear independent of changes in NSE, a biomarker of BBB integrity. Maintained accuracy and select increases in RT during hypoxic exercise may be related behavioral changes in caution., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The matching of oxygen supply to neural demand (i.e., neurovascular coupling (NVC)) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO), which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6% ± 0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using transcranial Doppler. Additional computerized cognitive testing was conducted separately to assess memory, executive function, attention, sensorimotor, and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6 ± 1.0 arbitrary units (AU)) compared with PLA (+0.2 ± 0.3 AU; p < 0.05). Memory performance (-6 ± 13 correct) significantly decreased (p < 0.05) in hypoxia while all other cognitive domains were unchanged in hypoxia for both PLA and NIT conditions (p > 0.05). MCA flow increased during Stroop similarly in normoxia (PLA +5 ± 6 cm·s(-1), NIT +7 ± 7 cm·s(-1)) and hypoxia (PLA +5 ± 9 cm·s(-1), NIT +6 ± 7 cm·s(-1)) (p < 0.05) and this increase was not altered by PLA or NIT (p > 0.05). In conclusion, acute hypoxia resulted in significant reductions in memory concomitant with preservation of executive function, attention, and sensorimotor function. Hypoxia had no effect on NVC. Acute NIT supplementation had no effect on NVC or cognitive performance in hypoxia.

Unlabelled: Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown., Purpose: Investigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia., Methods: 20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m(-2)) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio., Results: Aortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05)., Conclusions: Acute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: In premenopausal women, amenorrhea contributes to endothelial dysfunction. It is unknown whether this vascular functional change is associated with vascular structural change., Methods: This study examined regional and systemic vascular structure and function to gain insight into subclinical atherosclerotic risk in 10 amenorrheic athletes, 18 eumenorrheic athletes, and 15 recreationally active controls. Brachial flow-mediated dilation (FMD) and low flow mediated constriction (L-FMC) were used to measure global endothelial function. Carotid-femoral pulse wave velocity (PWV) was used to measure aortic stiffness. Doppler-ultrasound of the superficial femoral artery (SFA) was used to assess intima-media thickness (IMT) and vessel diameter as indicators of vascular remodeling., Results: Amenorrheic athletes had significantly lower brachial FMD adjusted for shear stimulus (6.9 ± 1.3%) compared with eumenorrheic athletes (11.0 ± 1.0%) and controls (11.0 ± 1.1%, p = 0.05). Brachial L-FMC (-1.8 ± 4.3%) and aortic PWV (5.0 ± 1.0 m/s) of amenorrheic athletes were similar to those of eumenorrheic athletes (L-FMC, -1.6 ± 4.6%; PWV, 4.6 ± 0.5 m/s) and controls (L-FMC, -1.5 ± 2.8%, p = 0.98; PWV, 5.4 ± 0.7 m/s, p = 0.15). SFA diameters were similar in amenorrheic athletes (5.7 ± 0.7 mm) and eumenorrheic athletes (5.7 ± 0.7 mm), but amenorrheic athletes had larger SFA diameters compared with controls (5.1 ± 0.6 mm, p = 0.04). In amenorrheic athletes, SFA IMT (0.31 ± 0.03 mm) was similar to that of eumenorrheic athletes (0.35 ± 0.07 mm) but significantly thinner compared to that of controls (0.38 ± 0.06, p = 0.01)., Conclusion: Vascular dysfunction in female amenorrheic athletes is not systemic. Parenthetically, amenorrhea may not prevent favorable peripheral vascular structural adaptations to habitual exercise training., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Exertional hypertension associated with acute high-intensity resistance exercise (RE) increases both intravascular and intracranial pressure (ICP), maintaining cerebrovascular transmural pressure. Carotid intravascular pressure pulsatility remains elevated after RE. Whether ICP also remains elevated after acute RE in an attempt to maintain the vessel wall transmural pressure is unknown. Optic nerve sheath diameter (ONSD), a valid proxy of ICP, was measured in 20 participants (6 female; 24 ± 4 yr, 24.2 ± 3.9 kg m(-)(2)) at rest (baseline), following a time-control condition, and following RE (5 sets, 5 repetition maximum bench press, 5 sets 10 repetition maximum biceps curls) using ultrasound. Additionally, intracranial hemodynamic pulsatility index (PI) was assessed in the ophthalmic artery (OA) by using Doppler. Aortic pulse wave velocity (PWV) was obtained from synthesized aortic pressure waveforms obtained via a brachial oscillometric cuff and carotid pulse pressure was measured by using applanation tonometry. Aortic PWV (5.2 ± 0.5-6.0 ± 0.7 m s(-1), P < 0.05) and carotid pulse pressure (45 ± 17-59 ± 19 mm Hg, P < 0.05) were significantly elevated post RE compared with baseline. There were no significant changes in ONSD (5.09 ± 0.7-5.09 ± 0.7 mm, P > 0.05) or OA flow PI (1.35 ± 0.2-1.38 ± 0.3, P > 0.05) following acute RE. In conclusion, during recovery from acute high-intensity RE, there are increases in aortic stiffness and extracranial pressure pulsatility in the absence of changes in ICP and flow pulsatility. These findings may have implications for alterations in cerebral transmural pressure and cerebral aneurysmal wall stress following RE.

This study examined the effects of moderate exercise-induced heat stress (EIHS) on vascular function, central hemodynamic load and indices of coronary perfusion. Vascular-hemodynamic measures were collected in 12 healthy men (aged 22±3 years) pre and post 100 minutes of moderate, intermittent exercise in two randomized conditions: heat stress (HS; wearing firefighter personal protective equipment (PPE)), and no heat stress (NHS; wearing a cooling shirt and equivalent PPE weight). Aortic blood pressure, reflected wave pressure (Pb), systolic (SPTI) and diastolic pressure time-integral (DPTI), and aortic stiffness were assessed before and after each condition. SPTI was significantly greater, and DPTI and Pb were significantly lower for HS-post compared to NHS-post (p<0.05). Pulse wave velocity was not different between conditions. In conclusion, EIHS does not affect aortic stiffness, but increases indices of myocardial work and reduces indices of coronary perfusion which may be related to chronotropic responses to EIHS. The mismatch between oxygen demand and oxygen supply may increase cardiac vulnerability to ischemia during strenuous work in the heat., (© The Author(s) 2015.)