Differences in cardiovascular risk factors associated with sex and gender identity, but not gender expression, in young, healthy cisgender adults.

Background: Sex differences exist in cardiovascular disease risk factors including elevated blood pressure and arterial stiffness, and decreased endothelial function in males compared to females. Feminine gender expression may be associated with elevated risk of acute coronary syndrome. However, no study has investigated the associations between sex, gender identity, and gender expression and cardiovascular disease risk factors in young adults. Methods: One hundred and thirty participants (22 ± 3 years) underwent assessments of hemodynamics, arterial stiffness [pulse wave velocity (PWV)], and brachial artery endothelial function (flow-mediated dilation; %FMD). Participants completed a questionnaire capturing sex category (50 male/80 female), gender identity category (49 men/79 women/2 non-binary), and aspects of gender expression assessed by the Bem Sex Role Inventory-30 (39 androgynous/33 feminine/29 masculine/29 undifferentiated). Sex/gender identity category groups were compared using unpaired t-tests and gender expression groups compared using one-way ANOVAs. Results: Resting systolic and mean arterial pressure (p < 0.01) were elevated in males vs. females. Central PWV was elevated in males [median (interquartile range): 6.4 (1.8) vs. 5.8 (2.2) m/s, p = 0.02]; however, leg and arm PWV were not different between sexes. %FMD was elevated in males vs. females, after accounting for a larger baseline artery diameter in males (8.8 ± 3.3% vs. 7.2 ± 3.1%, p = 0.02); since the majority of participants were cisgender, the same results were found examining gender identity (men vs. women). There were no differences across gender expression groups (p > 0.05). Conclusions: Sex/gender identity category, but not gender expression, influence cardiovascular risk factors (blood pressure, arterial stiffness, endothelial function) in cisgender adults; further research is needed in gender-diverse populations.

Effects of Lower Limb Heat Therapy, Exercise Training, or a Combined Intervention on Vascular Function: A Randomized Controlled Trial.

PURPOSE: To compare the effects of 8 weeks of no intervention (CON), lower limb heat therapy (HEAT), moderate-intensity exercise training (EX), or combined training and therapy (HEATEX) in young, healthy recreationally active adults. METHODS: Sixty participants (23 ± 3 years, 30 females) were randomly allocated into either CON (n = 15), HEAT (n = 15), EX (n = 14), or HEATEX (n = 16). The primary outcome was vascular function, assessed through brachial artery flow-mediated dilation tests (BA FMD). Secondary measures included arterial stiffness (pulse wave velocity, PWV); cardiorespiratory fitness (VO2peak); body composition; and quadriceps muscle strength. RESULTS: There were no differences in BA FMD between the groups before and after the interventions (all p > 0.05). Both interventions with a heating component were associated with within-group reductions in carotid-femoral PWV, and increases in absolute and relative VO2peak after 8 weeks (HEAT: ∆-0.27 [-0.53, -0.02] m/s, ∆0.18 [0.06, 0.29] L/min, ∆2.18 [0.60, 3.76] ml/kg/min, respectively; HEATEX: ∆-0.33 [-0.58, -0.09], ∆0.21 [0.11, 0.32] L/min, ∆2.59 [1.06, 4.12] ml/kg/min, respectively), but no between-group differences were observed (p = 0.25, p = 0.21, and p = 0.55, respectively). There was also a within-group decrease in body fat percentage with EX (∆-1.37 [-2.45, -0.29] %), but no changes in leg strength in any of the groups (p = 0.79). CONCLUSIONS: This randomized controlled trial is the first to examine the efficacy of lower limb heating against traditionally prescribed exercise training. In our young cohort, 8 weeks of training and/or therapy was insufficient to improve vascular function. More intense protocols and longer interventions involving lower limb heating may be required to elicit improvements in health outcomes.

Modulation of Vascular Health by Hormonal Contraceptives and Exercise in Young Women: Using the FITT Principles Methodological Framework.

ABSTRACT: Cardiovascular health is governed by responses of the heart and vasculature to stimuli, including exercise and synthetic hormones in hormonal contraception. In this review, we draw similarities between research examining the effects of exercise training and hormonal contraception on vascular health, aligned using FITT principles (frequency, intensity, type, and time) as a methodological framework, and outline future directions for research.

Menstrual and oral contraceptive pill cycles minimally influence vascular function and associated cellular regulation in premenopausal females.

BACKGROUND: Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. METHODS: Forty-nine premenopausal females (n=17 NAT, n=17 2nd generation OCP, n=15 3rd generation OCP) participated in two randomized order visits in the low (LH: early follicular/placebo) and high (HH: mid-luteal/active) hormone cycle phases. BA and femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test) and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha (ERα) protein content. RESULTS: BA FMD was elevated in the HH versus LH phase, regardless of group (HH:7.7±3.5%, LH:7.0±3.3%, p=0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH:7.6±2.6%, LH:7.1±2.6%, p=0.052, d=0.35). SFA FMD, BA and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. CONCLUSIONS: NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter.

Cardiorespiratory Fitness Benefits of High-Intensity Interval Training After Stroke: A Randomized Controlled Trial.

BACKGROUND: Limited evidence supports the effects of short-interval high-intensity interval training (HIIT) for improving cardiorespiratory fitness (V̇O2peak) after stroke. We aimed to compare the effects of 12 weeks of short-interval HIIT versus moderate-intensity continuous training (MICT) on V̇O2peak, cardiovascular risk factors, and mobility outcomes among individuals ≥6 months poststroke. METHODS: This study was a multi-site, 12-week randomized controlled trial (NCT03614585) with an 8-week follow-up. Participants were randomized into 3 d/wk of HIIT (10×1 minute 80%-100% heart rate reserve interspersed with 1 minute 30% heart rate reserve [19 minutes]) or MICT (20-30 minutes 40%-60% heart rate reserve). Secondary outcomes of the trial, including V̇O2peak, cardiovascular risk factors (carotid-femoral pulse wave velocity, blood pressure, and waist-hip ratio), and mobility (6-minute walk test, 10 m gait speed), were reported. Linear mixed model analyses with a group×study time point interaction evaluated between-group differences. RESULTS: Of the 305 potential participants, 82 consented (mean [SD] age 64.9 [9.3] years, 32 females [39%], 1.8 [1.2] years poststroke) and were randomized to HIIT (n=42, mean [SD] baseline V̇O2peak 17.3 [5.9] mL/kg·min) or MICT (n=40, mean [SD] baseline V̇O2peak 17.2 [6.0] mL/kg·min). Participants attended 82% of visits (n=2417/2952). No adverse events occurred during the study period. A significant group×study time point interaction was found (χ2=8.46; P=0.015) for V̇O2peak at 12 weeks (mean difference, 1.81 [95% CI, 0.58-3.04]; P=0.004) whereby the HIIT group had greater gains in V̇O2peak (∆3.52 mL/kg·min [95% CI, 2.47-4.57]; P<0.001) compared with the MICT group (∆1.71 mL/kg·min [95% CI, 0.55-2.86]; P=0.001). There was no between-group difference in V̇O2peak (mean difference, 1.08 [95% CI, -0.26 to 2.42]; P=0.11) at 8-week follow-up. No group×study time point interactions were found for cardiovascular risk factors or mobility outcomes. CONCLUSIONS: Short-interval HIIT may be an effective alternative to MICT for improving V̇O2peak at 12 weeks postintervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03614585.

Acute partial sleep restriction does not impact arterial function in young and healthy humans.

Habitual short sleep durations are associated with several cardiovascular diseases. Experimental research generally supports these findings as metrics of arterial function are impaired after complete deprivation of sleep and after longer periods of partial sleep restriction. The acute influence of a single instance of partial sleep restriction (PSR), however, has not been defined. We evaluated arterial structure and function among 32 university-aged participants on two occasions: once after normal habitual sleep (NS), and again the morning after an acute partial sleep restriction (PSR) intervention involving only 3 h of sleep for a single night. Endothelial function was measured using ultrasonography at the brachial artery via flow-mediated dilatation (FMD), and a ramp peak oxygen uptake test was used to evaluate cardiorespiratory fitness. Blood samples were collected from a subset of participants to investigate the influence of circulatory factors on cellular mechanisms implicated in endothelial function. Sleep duration was lower after a night of PSR compared to NS (P < 0.001); however, there were no appreciable differences in any haemodynamic outcome between conditions. FMD was not different between NS and PSR (NS: 6.5 ± 2.9%; PSR: 6.3 ± 2.9%; P = 0.668), and cardiorespiratory fitness did not moderate the haemodynamic response to PSR (all P > 0.05). Ex vivo cell culture results aligned with in vivo data, showing that acute PSR does not alter intracellular processes involved in endothelial function. No differences in arterial structure or function were observed between NS and acute PSR in healthy and young participants, and cardiorespiratory fitness does not modulate the arterial response to acute sleep restriction.

Targeting skeletal muscle health with exercise in people with type 1 diabetes: A protocol for HOMET1D, a prospective observational trial with matched controls.

INTRODUCTION: Individuals with type 1 diabetes (T1D) experience a complex set of alterations to skeletal muscle metabolic, neuromuscular, and vascular health; collectively referred to as diabetic myopathy. While the full scope of diabetic myopathy is still being elucidated, evidence suggests that even when individuals with T1D are physically active, indices of myopathy still exist. As such, there is a question if adherence to current physical activity guidelines elicits improvements in skeletal muscle health indices similarly between individuals with and without T1D. The objectives of this trial are to: 1) compare baseline differences in skeletal muscle health between adults with and without T1D, 2) examine the association between participation in a home-based exercise program, detraining, and retraining, with changes in skeletal muscle health, and 3) examine the roles of age and sex on these associations. METHODS AND ANALYSIS: This will be a prospective interventional trial. Younger (18-30 years) and older (45-65 years) males and females with T1D and matched individuals without T1D will engage in a four-phase, 18-week study sequentially consisting of a one-week lead-in period, 12-week exercise training program, one-week detraining period, and four-week retraining period. The exercise program will consist of aerobic and resistance exercise based on current guidelines set by Diabetes Canada. Metabolic, neuromuscular, and vascular outcome measures will be assessed four times: at baseline, post-exercise program, post-detraining, and post-retraining. Differences in baseline metrics between those with and without T1D will be examined with independent sample t-tests, and with two-way analyses of variance for age- and sex-stratified analyses. Changes across the duration of the study will be examined using mixed-model analyses. DISSEMINATION: Findings from this research will be shared locally and internationally with research participants, clinicians, diabetes educators, and patient advocacy organizations via in-person presentations, social media, and scientific fora. TRIAL REGISTRATION NUMBER: NCT05740514.

Cardiorespiratory Fitness Benefits of Long-Term Maintenance-Phase Cardiac Rehabilitation in Males and Females: A Retrospective Cohort Study.

Purpose: This study investigated if associations exist between enrolment delay and VO2peak over five years of maintenance-phase cardiac rehabilitation (CR) in males and females. Method: Data were extracted from the records of participants who had enrolled for ≥ 1 year in CR and completed ≥ 2 cardiopulmonary exercise tests. Mixed model analyses examined VO2peak trajectories for up to five years of enrolment. Interactions between enrolment delay × enrolment duration, baseline age × enrolment duration, and baseline VO2peak × enrolment duration were explored for inclusion in the model. Results: The charts of 151 males (aged 63.9 ± 9.4 y) and 32 females (aged 65.3 ± 9.0 y) were included in the analyses. The enrolment delay following a cardiovascular event was 1.8 ± 3.0 years for males and 1.3 ± 1.7 years for females. No associations were found between enrolment delay × enrolment duration on VO2peak in males (ß[SEj, 0.07[0.05]; 95% CI -0.02, 0.16, p = 0.12) or in females (ß[SE], 0.07[0.13j; 95% CI -0.18, 0.33, p = 0.57), but predicted trajectories suggest clinically significantly improvements in VO2 peak (range, 1.3 to 1.6 mL/kg/min). Conclusions: Early enrolment in CR is recommended and encouraged, but the benefits of long-term CR are possible despite delays.

Objectif: étudier les associations éventuelles entre le retard d'inscription et la consommation maximale d'oxygène (VO2 max) pendant une phase d'entretien de cinq ans de la réadaptation cardiaque (RC) chez des hommes et des femmes. Méthodologie: données extraites des dossiers des participants inscrits en RC pendant au moins un an et qui ont effectué au moins deux épreuves d'effort cardiorespiratoire. Par des analyses en modèle mixte, les chercheurs ont examiné les trajectoires de VO2 max pendant une période d'inscription maximale de cinq ans. Ils ont exploré les interactions entre le retard d'inscription × la durée d'inscription, entre l'âge au départ × la durée d'inscription et entre la VO2 max au départ × la durée d'inscription pour les inclure dans le modèle. Résultats: les dossiers de 151 hommes (de 63,9 ± 9,4 ans) et de 32 femmes (de 65,3 ± 9,0 ans) ont été inclus dans les analyses. Après un événement cardiovasculaire, les hommes présentaient un retard d'inscription de 1,8 ± 3,0 ans et les femmes, de 1,3 ± 1,7 an. Les chercheurs n'ont constaté aucune association entre le retard d'inscription × la durée d'inscription et la VO2 max chez les hommes (ß[ET], 0,7[0,05]; IC à 95 % −0,02, 0,16, p = 0,12) ni chez les femmes (ß[ET], 0,07[0,13]; IC à 95 % −0,18, 0,33, p = 0,57), mais les trajectoires anticipées laissent supposer des améliorations cliniquement significatives de la VO2 max (plage de 1,3 à 1,6 mL/kg/min). Conclusions: il est recommandé et encouragé de s'inscrire rapidement en RC, mais la RC à long terme peut comporter des avantages malgré les retards d'inscription.

The effects of water temperature on cerebral blood flow during aquatic exercise.

PURPOSE: Recent studies suggest that episodic increases in cerebral blood flow (CBF) may contribute to the improvement in brain health associated with exercise training. Optimising CBF during exercise may enhance this benefit. Water immersion in ~ 30-32 °C augments CBF at rest and during exercise; however, the impact of water temperature on the CBF response has not been investigated. We hypothesised that cycle ergometry in water would increase CBF compared to land-based exercise, and that warm water would attenuate the CBF benefits. METHODS: Eleven young heathy participants (nine males; 23.8 ± 3.1 yrs) completed 30 min of resistance-matched cycle exercise in three separate conditions; non-immersion (Land), 32 °C and 38 °C water immersion up to the level of the waist. Middle cerebral artery velocity (MCAv), blood pressure, and respiratory measures were assessed throughout the exercise bouts. RESULTS: Core temperature was significantly higher in the 38 °C immersion than 32 °C (+ 0.84 ± 0.24 vs + 0.04 ± 0.16, P < 0.001), whilst mean arterial pressure was lower during 38 °C exercise compared to Land (84 ± 8 vs 100 ± 14 mmHg, P < 0.001) and 32 °C (92 ± 9, P = 0.03). MCAv was higher in 32 °C immersion compared to the Land and 38 °C conditions throughout the exercise bout (68 ± 10 vs 64 ± 11 vs 62 ± 12 cm/s, P = 0.03 and P = 0.02, respectively). CONCLUSION: Our findings suggest that cycle exercise in warm water attenuates the beneficial impact of water immersion on CBF velocity due to redistribution of blood flow to subserve thermoregulatory demand. Our findings suggest that, whilst water-based exercise can have beneficial effects on cerebrovascular function, water temperature is a key determinant of this benefit.

Biological sex does not influence the peak cardiac output response to twelve weeks of sprint interval training.

Sprint interval training (SIT) increases peak oxygen uptake (V̇O2peak) but the mechanistic basis is unclear. We have reported that 12 wk of SIT increased V̇O2peak and peak cardiac output (Q̇peak) and the changes in these variables were correlated. An exploratory analysis suggested that Q̇peak increased in males but not females. The present study incorporated best practices to examine the potential influence of biological sex on the Q̇peak response to SIT. Male and female participants (n = 10 each; 21 ± 4 y) performed 33 ± 2 sessions of SIT over 12 wk. Each 10-min session involved 3 × 20-s 'all-out' sprints on an ergometer. V̇O2peak increased after SIT (3.16 ± 1.0 vs. 2.89 ± 1.0 L/min, η2p = 0.53, p < 0.001) with no sex × time interaction (p = 0.61). Q̇peak was unchanged after training (15.2 ± 3.3 vs. 15.1 ± 3.0 L/min, p = 0.85), in contrast to our previous study. The peak estimated arteriovenous oxygen difference increased after training (204 ± 30 vs. 187 ± 36 ml/L, p = 0.006). There was no effect of training or sex on measures of endothelial function. We conclude that 12 wk of SIT increases V̇O2peak but the mechanistic basis remains unclear. The capacity of inert gas rebreathing to assess changes in Q̇peak may be limited and invasive studies that use more direct measures are needed.

Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology.

Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.

The impacts of endogenous progesterone and exogenous progestin on vascular endothelial cell, and smooth muscle cell function: A narrative review.

Vascular endothelial and smooth muscle cell dysfunction proceed the development of numerous vascular diseases, such as atherosclerosis. Both estrogen and progesterone receptors are present on vascular endothelial and smooth muscle cells, and therefore it has been postulated that these compounds may affect vascular function. It has been well-established that estrogen is a vasoprotective compound, however, the effects of progesterone on vascular function are not well understood. This narrative review summarizes the current research investigating the impact of both endogenous progesterone, and exogenous synthetic progestin on vascular endothelial and smooth muscle cell function and identifies discrepancies on their effects in vitro and in vivo. We speculate that an inverted-U dose response curve may exist between nitric oxide bioavailability and progesterone concentration, and that the androgenic properties of a progestin may influence vascular function. Future research is needed to discern the effects of both endogenous progesterone and exogenous progestin on vascular endothelial and smooth muscle cell function with consideration for the impacts of progesterone/progestin dose, and progestin type.

The impact of natural menstrual cycle and oral contraceptive pill phase on substrate oxidation during rest and acute submaximal aerobic exercise.

Previous research has identified sex differences in substrate oxidation during submaximal aerobic exercise including a lower respiratory exchange ratio (RER) in females compared with males. These differences may be related to differences in sex hormones. Our purpose was to examine the impact of the natural menstrual cycle (NAT) and second- and third-generation oral contraceptive pill (OCP2 and OCP3) cycle phases on substrate oxidation during rest and submaximal aerobic exercise. Fifty female participants (18 NAT, 17 OCP2, and 15 OCP3) performed two experimental trials that coincided with the low (i.e., nonactive pill/early follicular) and the high hormone (i.e., active pill/midluteal) phase of their cycle. RER and carbohydrate and lipid oxidation rates were determined from gas exchange measurements performed during 10 min of supine rest, 5 min of seated rest, and two 8-min bouts of submaximal cycling exercise at ∼40% and ∼65% of peak oxygen uptake (V̇o2peak). For all groups, there were no differences in RER between the low and high hormone phases during supine rest (0.73 ± 0.05 vs. 0.74 ± 0.05), seated rest (0.72 ± 0.04 vs. 0.72 ± 0.04), exercise at 40% (0.77 ± 0.04 vs. 0.78 ± 0.04), and 65% V̇o2peak (0.85 ± 0.04 vs. 0.86 ± 0.03; P > 0.19 for all). Similarly, carbohydrate and lipid oxidation rates remained largely unchanged across phases during both rest and exercise, apart from higher carbohydrate oxidation in NAT vs. OCP2 at 40% V̇o2peak (P = 0.019) and 65% V̇o2peak (P = 0.001). NAT and OCPs do not appear to largely influence substrate oxidation at rest and during acute submaximal aerobic exercise.NEW & NOTEWORTHY This study was the first to examine the influence of NAT and two generations of OCPs on substrate oxidation during rest and acute submaximal aerobic exercise. We reported no differences across cycle phases or groups on RER, and minimal impact on carbohydrate or lipid oxidation apart from an increase in carbohydrate oxidation in NAT compared with OCP2 during exercise. Based on these findings, NAT/OCP phase controls may not be necessary in studies investigating substrate oxidation.

Physical Activity Trajectories in Early Childhood: Investigating Personal, Environmental, and Participation Factors.

INTRODUCTION/PURPOSE: To determine personal, environmental, and participation factors that predict children's physical activity (PA) trajectories from preschool through to school years. METHODS: Two hundred seventy-nine children (4.5 ± 0.9 yr, 52% boys) were included in this study. Physical activity was collected via accelerometry at six different timepoints over 6.3 ± 0.6 yr. Time-stable variables were collected at baseline and included child's sex and ethnicity. Time-dependent variables were collected at six timepoints (age, years) and included household income (CAD), parental total PA, parental influence on PA, and parent-reported child's quality of life, child's sleep, and child's amount of weekend outdoor PA. Group-based trajectory modeling was applied to identify trajectories of moderate-to-vigorous PA (MVPA) and total PA (TPA). Multivariable regression analysis identified personal, environmental, and participation factors associated with trajectory membership. RESULTS: Three trajectories were identified for each of MVPA and TPA. Group 3 in MVPA and TPA expressed the most PA over time, with increased activity from timepoints 1 to 3, and then declining from timepoints 4 to 6. For the group 3 MVPA trajectory, male sex (ß estimate, 3.437; P = 0.001) and quality of life (ß estimate, 0.513; P < 0.001) were the only significant correlates for group membership. For the group 3 TPA trajectory, male sex (ß estimate, 1.970; P = 0.035), greater household income (ß estimate, 94.615; P < 0.001), and greater parental total PA (ß estimate, 0.574; P = 0.023) increased the probability of belonging to this trajectory group. CONCLUSIONS: These findings suggest a need for interventions and public health campaigns to increase opportunities for PA engagement in girls starting in the early years. Policies and programs to address financial inequities, positive parental modeling, and improving quality of life are also warranted.

Effects of exercise during water immersion on arterial function in humans.

Flow-mediated dilation (FMD) provides a valid bioassay of vascular function in humans. Although water immersion induces hemodynamic effects that modify brachial artery shear stress, it is unclear whether water-based exercise modifies FMD. We hypothesized that exercise in 32°C water would decrease brachial artery shear and FMD relative to land-based exercise, whereas exercise in 38°C would increase brachial shear and FMD. Ten healthy participants (8 males; 23.9 ± 3.3 yr) completed 30 min of resistance-matched cycle exercise in three separate conditions: on land and in 32°C and 38°C water. Brachial artery shear rate area under the curve (SRAUC) was measured throughout each condition, with FMD measured pre- and postexercise. Brachial SRAUC increased during exercise in all conditions and was highest across the 38°C condition compared with Land and 32°C conditions (38°C: 27,507 ± 8,350 vs. Land: 9,908 ± 4,738 vs. 32°C: 13,840 ± 5,861 1/s, P < 0.001). Retrograde diastolic shear was greater during 32°C than both Land and 38°C conditions (32°C:-3,869 ± 2,198 vs. Land:-1,602 ± 1,334 vs. 32°C:-1,036 ± 1,754, P < 0.01). FMD increased as a result of 38°C (6.2 ± 1.9 vs. 8.5 ± 2.7%, P = 0.03), with no change in the Land exercise (6.3 ± 2.4 vs. 7.7 ± 2.4%, P = 0.10) or 32°C condition (6.4 ± 3.2 vs. 6.7 ± 3.2%, P = 0.99). Our findings indicate that cycle exercise in hot water attenuates retrograde shear, increases antegrade shear, and FMD. Exercise in 32°C water induces central hemodynamic changes relative to land-based exercise, but these do not translate to increases in FMD in either condition, likely due to the impact of increased retrograde shear. Our findings indicate that modification of shear has direct acute impacts on endothelial function in humans.

Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review.

Osteoarthritis (OA) is a highly prevalent condition characterized by degradation of the joints. OA and cardiovascular disease (CVD) are leading contributors to disease burden worldwide, with a high level of overlap between the risk factors and occurrence of both conditions. Chief among the risk factors that contribute to OA and CVD are sex and age, which are both independent and interacting traits. Specifically, the prevalence of both conditions is higher in older women, which may be mediated by the occurrence of menopause. Menopause represents a significant transition in a women's life, and the rapid decline in circulating sex hormones, estrogen and progesterone, leads to complex physiological changes. Declines in hormone levels may partially explain the increase in prevalence of OA and CVD in post-menopausal women. In theory, the use of hormone therapy (HT) may buffer adverse effects of menopause; however, it is unclear whether HT offers protective effects for the onset or progression of these diseases. Studies have shown mixed results when describing the influence of HT on disease risk among post-menopausal women, which warrants further exploration. The roles that increasing age, female sex, HT, and CVD play in OA risk demonstrate that OA is a multifaceted condition. This review provides a timely consolidation of current literature and suggests aims for future research directions to bridge gaps in the understanding of how OA, CVD, and HT interact in post-menopausal women.

Decreased Diastolic Blood Pressure and Average Grip Strength in Adults With Type 1 Diabetes Compared With Controls: An Analysis of Data From the Canadian Longitudinal Study on Aging.

OBJECTIVES: Our aim in this study was to determine whether aging individuals with type 1 diabetes (T1D) have differences in cardiovascular health, assessed by blood pressure, and skeletal muscle function, assessed by grip strength, compared with matched nondiabetic controls (CON). METHODS: This investigation was a retrospective cohort analysis using baseline and 3-year follow-up data from the Canadian Longitudinal Study on Aging. Bivariate and multivariate regression analyses were used to examine the association between sociodemographic, health, behavioural and T1D-specific variables on blood pressure and grip strength in T1D and CON groups. Generalized estimating equations were used to model the average population changes in blood pressure and grip strength from baseline to follow up. RESULTS: The sample included 126 individuals (63 T1D and 63 CON). Systolic blood pressure was not significantly different between groups at baseline or follow up (p>0.05). However, compared with CON, diastolic blood pressure was significantly lower at both time-points in the T1D group (p<0.001). Grip strength was consistently lower among persons with T1D (p=0.03). In the multivariate regression model, body mass index, age and sex were significantly associated with diastolic blood pressure and grip strength in both groups. In the T1D group, disease duration accounted for a large proportion of the variance in diastolic blood pressure and grip strength (17% and 9%, respectively). The rate of decline in diastolic blood pressure and grip strength did not differ between groups (p>0.05). CONCLUSIONS: Diastolic blood pressure and grip strength appear to be consistently lower and differentially regulated in individuals with T1D vs CON. Aging individuals with T1D may be at risk of premature morbidity and mortality.

Cardiovascular responses to high-intensity stair climbing in individuals with coronary artery disease.

Exercise-based cardiac rehabilitation leads to improvements in cardiovascular function in individuals with coronary artery disease. The cardiac effects of coronary artery disease (CAD) can be quantified using clinical echocardiographic measures, such as ejection fraction (EF). Measures of cardiovascular function typically only used in research settings can provide additional information and maybe more sensitive indices to assess changes after exercise-based cardiac rehabilitation. These additional measures include endothelial function (measured by flow-mediated dilation), left ventricular twist, myocardial performance index, and global longitudinal strain. To investigate the cardiovascular response to 12 week of either traditional moderate-intensity (TRAD) or stair climbing-based high-intensity interval (STAIR) exercise-based cardiac rehabilitation using both clinical and additional measures of cardiovascular function in individuals with CAD. Measurements were made at baseline (BL) and after supervised (4wk) and unsupervised (12 week) of training. This study was registered as a clinical trial at clinicaltrials.gov (NCT03235674). Participants were randomized into either TRAD (n = 9, 8M/1F) and STAIR (n = 9, 8M/1F). There was a training-associated increase in one component of left ventricular twist: Cardiac apical rotation (TRAD: BL: 5.6 ± 3.3º, 4 week: 8.0 ± 3.9º, 12 week: 6.2 ± 5.1º and STAIR: BL: 5.1 ± 3.6º, 4 week: 7.4 ± 3.9º, 12 week: 7.8 ± 2.8º, p (time) = 0.03, η2  = 0.20; main effect) and post-hoc analysis revealed a difference between BL and 4 week (p = 0.02). There were no changes in any other clinical or additional measures of cardiovascular function. The small increase in cardiac apical rotation observed after 4 weeks of training may indicate an early change in cardiac function. A larger overall training stimulus may be needed to elicit other cardiovascular function changes.

What are the effects of acute exercise and exercise training on cerebrovascular hemodynamics following stroke? A systematic review and meta-analysis.

Limited data exist regarding the effects of acute exercise and exercise training on cerebrovascular hemodynamic variables after stroke. This systematic review and meta-analysis 1) examined the effects of acute exercise and exercise training on cerebrovascular hemodynamic variables reported in the stroke exercise literature and 2) synthesized the peak middle cerebral artery blood velocity (MCAv) achieved during an acute bout of moderate-intensity exercise in individuals after stroke. Six databases (Medline, Embase, Web of Science, CINAHL, PsycINFO, AMED) were searched from inception to December 1st, 2021 for studies that examined the effect of acute exercise or exercise training on cerebrovascular hemodynamics in adults after stroke. Two reviewers conducted title and abstract screening, full-text evaluation, data extraction, and quality appraisal. Random-effects models were used in meta-analysis. Nine studies, including four acute exercise (n = 61) and five exercise training studies (n = 193), were included. Meta-analyses were not statistically feasible for several cerebrovascular hemodynamic variables. Descriptive analysis reveals that exercise training may increase cerebral blood flow and cerebrovascular reactivity to carbon dioxide among individuals after stroke. Meta-analysis of three acute exercise studies revealed no significant changes in MCAv during acute moderate-intensity exercise [n = 48 participants, mean difference = 5.2 cm/s, 95% confidence interval (CI) [-0.6, 11.0], P = 0.08] compared with resting MCAv values. This review suggests that individuals after stroke may have attenuated cerebrovascular hemodynamics as measured by the MCAv during acute moderate-intensity exercise. Aerobic exercise training is beneficial for improving cardiovascular health and function after stroke; higher-quality research utilizing agreed-upon hemodynamic variables is needed to synthesize the effects of exercise training on poststroke cerebrovascular hemodynamics.

Examination of Sex-Specific Participant Inclusion in Exercise Physiology Endothelial Function Research: A Systematic Review.

Background: To combat historical underrepresentation of female participants in research, guidelines have been established to motivate equal participation by both sexes. However, the pervasiveness of female exclusion has not been examined in vascular exercise physiology research. The purpose of this study was to systematically quantify the sex-specific prevalence of human participants and identify the rationales for sex-specific inclusion/exclusion in research examining the impact of exercise on vascular endothelial function. Methods: A systematic search was conducted examining exercise/physical activity and vascular endothelial function, assessed via flow mediated dilation. Studies were categorized by sex: male-only, female-only, or mixed sex, including examination of the sample size of males and females. Analysis was performed examining sex-inclusion criteria in study design and reporting and rationale for inclusion/exclusion of participants on the basis of sex. Changes in proportion of female participants included in studies were examined over time in 5 year cohorts. Results: A total of 514 studies were identified, spanning 26 years (1996-2021). Of the total participants, 64% were male and 36% were female, and a male bias was identified (32% male-only vs. 12% female-only studies). Proportions of female participants in studies remained relatively constant in the last 20 years. Male-only studies were less likely to report sex in the title compared to female-only studies (27 vs. 78%, p < 0.001), report sex in the abstract (72 vs. 98%, p < 0.001) and justify exclusion on the basis of sex (15 vs. 55%, p < 0.001). Further, male-only studies were more likely to be conducted in healthy populations compared to female-only studies (p = 0.002). Qualitative analysis of justifications identified four themes: sex-specific rationale or gap in the literature, exclusion of females based on the hormonal cycle or sex-differences, maintaining congruence with the male norm, and challenges with recruitment, retention and resources. Conclusions: This systematic review provides the first analysis of sex-based inclusion/exclusion and rationale for sex-based decisions in human vascular exercise physiology research. These findings contribute to identifying the impact of research guidelines regarding inclusion of males and females and the perceived barriers to designing studies with equal sex participation, in an effort to increase female representation in vascular exercise physiology research. Systematic Review Registration: CRD42022300388.