Physical performance changes as clues to late-life blood pressure changes with advanced age: the osteoporotic fractures in men study.

OBJECTIVES: This study examined whether changes in late-life physical performance are associated with contemporaneous changes in blood pressure (BP) in older men. DESIGN: prospective cohort study over 7 years. SETTING AND PARTICIPANTS: Physical performance (gait speed, grip strength, chair stand performance) and clinic-measured BP at baseline and at least one follow-up (year 7 or 9) were assessed in 3,135 men aged ≥65 y enrolled in the Osteoporotic Fractures in Men Study (MrOS). METHODS: Generalized estimating equation analysis of multivariable models with standardized point estimates (ß [95% CI]) described longitudinal associations between physical performance and BP changes in participants overall, and stratified by baseline cardiovascular disease (CVD), antihypertensive medication use (none, ≥1), and enrollment age (<75 years; ≥75 years). RESULTS: Overall, positive associations (z-score units) were found between each increment increase in gait speed and systolic (SBP) (0.74 [0.22, 1.26]) and grip strength (0.35 [0.04, 0.65]) or gait speed (0.55 [0.24, 0.85]) with diastolic (DBP). Better grip strength and chair stand performance over time were associated with 1.83 [0.74, 2.91] and 3.47 [0.20, 6.74] mmHg higher SBP, respectively in men with CVD at baseline (both interaction P < .05). Gait speed increases were associated with higher SBP in men without CVD (0.76 [0.21, 1.32]), antihypertensive medication non-users (0.96 [0.30, 1.62]), aged <75 years (0.73 [0.05, 1.41]) and ≥75 years (0.76 [0.06, 1.47]). Similar positive, but modest associations for DBP were observed with grip strength in men with CVD, antihypertensive medication non-users, and aged <75 years, and with gait speed in men without CVD, aged <75 years, and irrespective of antihypertensive medication use. CONCLUSION: In older men, better physical performance is longitudinally associated with higher BP. Mechanisms and implications of these seemingly paradoxical findings, which appears to be modified by CVD status, antihypertensive medication use, and age, requires further investigation.

The MindMoves Trial: Cross-Sectional Analyses of Baseline Vascular Risk and Cognition in Older Women with Cardiovascular Disease.

Background: Vascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and stroke, increase the risk of Alzheimer's disease and cognitive impairment. Serum biomarkers, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), may be indicators of cognitive health. Objective: We examined whether vascular risk was associated with levels of cognition and serum biomarkers in older women with cardiovascular disease (CVD). Methods: Baseline data from a lifestyle trial in older women (n = 253) with CVD (NCT04556305) were analyzed. Vascular risk scores were calculated for ASCVD (ASCVD risk estimator) and stroke (CHA2DS2-VASc) based on published criteria. Cognition-related serum biomarkers included BDNF, VEGF, and IGF-1. Cognition was based on a battery of neuropsychological tests that assessed episodic memory, semantic memory, working memory, and executive function. A series of separate linear regression models were used to evaluate associations of vascular risk scores with outcomes of cognition and serum biomarkers. All models were adjusted for age, education level, and racial and ethnic background. Results: In separate linear regression models, both ASCVD and CHA2DS2-VASc scores were inversely associated with semantic memory (ß= -0.22, p = 0.007 and ß= -0.15, p = 0.022, respectively), with no significant findings for the other cognitive domains. There were no significant associations between vascular risk scores and serum biomarkers. Conclusions: Future studies should prospectively examine associations between vascular risk and cognition in other populations and additionally consider other serum biomarkers that may be related to vascular risk and cognition.

Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial.

BACKGROUND: Older adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL). OBJECTIVE: We propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment. METHODS: This Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models. DISCUSSION: This Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS. TRIAL REGISTRATION NUMBER: NCT05930821.

A quantitative feedback intervention to reduce binge drinking in young adults.

OBJECTIVE: Existing binge drinking reduction interventions such as brief intervention and personalized normative feedback have shown modest impact. The purpose of this study was to evaluate the feasibility (recruitment and retention rates), acceptability, and preliminary efficacy testing of a short-term "know your numbers (KYN)" intervention on motivating young adults to reduce their engagement in binge drinking. METHOD: Young adults (N=94, mean age 21 years) with a history of binge drinking received a 4-week KYN intervention that included information about their U.S. Alcohol Use Disorders Test (USAUDIT) scores and the alcohol biomarker phosphatidylethanol (PEth) level in relationship to different risk levels of alcohol use. At baseline and 4-weeks, measures included USAUDIT scores, PEth levels, motivation (Alcohol Contemplation Ladder) and other drinking measures. Focus groups were conducted at 4-weeks for feedback on the KYN approach. RESULTS: The recruitment rate was 82.26% (retention rate 76.9%). At 4-weeks there was a 62% increase in contemplation scores (indicating higher motivation), a decrease in USADUIT scores with an increase in the percent of participants classified as low-risk drinkers. No differences were found between baseline and 4-week PEth levels or number of binge episodes. Focus group results revealed satisfaction with the KYN approach but the need to understand how PEth levels and USAUDIT scores corresponded to health consequences and alcohol use levels. CONCLUSIONS: Results from this pilot study support the acceptability and potential use of a KYN approach in helping young adults understand their drinking levels.

The six-minute step test can predict COPD exacerbations: a 36-month follow-up study.

The six-minute step test (6MST) has been shown to be effective in assessing exercise capacity in individuals with COPD regardless of severity and, despite its easy execution, accessibility and validity, information on the prognostic power of this test remains uncertain. The aim of this study is to investigate whether the 6MST can predict the occurrence of exacerbations in patients with COPD. This is a prospective cohort study with a 36-month follow-up in patients with COPD. All patients completed a clinical assessment, followed by pulmonary function testing and a 6MST. The 6MST was performed on a 20 cm high step; heart rate, blood pressure, oxygen saturation, BORG dyspnea and fatigue were collected. Sixty-four patients were included in the study, the majority being elderly men. Performance on the 6MST demonstrated lower performance compared to normative values proposed in the literature, indicating a reduced functional capacity. Kaplan Meier analysis revealed that ≤ 59 steps climbed during the 6MST was a strong predictor of COPD exacerbation over a 36-month follow-up. We have identified a minimal threshold number of steps (≤ 59) obtained through the 6MST may be able predict the risk of exacerbations in patients with COPD.

The Impact of Light Physical Activity, Sedentary Behavior and Cardiorespiratory Fitness in Extending Lifespan and Healthspan Outcomes: How Little is Still Significant? A Narrative Review.

To describe the relationship between mortality and measures of low intensity physical activity (LIPA) as well as sedentary behavior (SB), and cardiorespiratory fitness (CRF). Study selection was performed through multiple database searches from January 1, 2000 until May 1, 2023. Seven LIPA studies, 9 SB studies, and 8 studies CRF studies were selected for primary analysis. LIPA and non-SB follow a reverse J shaped curve with mortality. The greatest benefits occur initially, and the rate of mortality reduction slows with increasing physical activity. Increasing CRF reduces mortality although the dose response curve is uncertain. For special populations such as individuals with, or at high risk of developing cardiovascular disease the benefit from exercise is heightened. LIPA, decreased SB and higher CRF lead to reductions in mortality and improved quality of life. Individualized counseling on the benefits of any amount of physical activity may increase compliance and serve as a starting point for lifestyle modifications.

Feasibility, impact, and priority of key strategies to enhance diverse and inclusive training programs in clinical and translational research: A mixed methods study.

Background: Enhancing diversity in the scientific workforce is a long-standing issue. This study uses mixed methods to understand the feasibility, impact, and priority of six key strategies to promote diverse and inclusive training and contextualize the six key strategies across Clinical and Translational Science Awards (CTSAs) Program Institutions. Methods: Four breakout sessions were held at the NCATS 2020 CTSA Program annual meeting focused on diversity, equity, and inclusion (DEI) efforts. This paper focuses on the breakout session for Enhancing DEI in Translational Science Training Programs. Data were analyzed using a mixed methods convergent approach. The quantitative strand includes the online polling results. The qualitative strand includes the breakout session and the chat box in response to the training presentation. Results: Across feasibility, impact, and priority questions, prioritizing representation ranked number 1. Building partnerships ranked number 2 in feasibility and priority, while making it personal ranked number 2 for impact. Across each strategy, rankings supported the qualitative data findings in feasibility through shared experiences, impact in the ability to increase DEI, and priority rankings in comparison to the other strategies. No divergence was found across quantitative and qualitative data findings. Conclusion: Findings provide robust support for prioritizing representation as a number one strategy to focus on in training programs. Specifically, this strategy can be operationalized through integration of community representation, diversity advocates, and adopting a holistic approach to recruiting a diverse cadre of scholars into translational science training programs at the national level across CTSAs.

Mentoring strategies to support diversity in research-focused junior faculty: A scoping review.

Objective: The purpose of this scoping review is two-fold: to assess the literature that quantitatively measures outcomes of mentorship programs designed to support research-focused junior faculty and to identify mentoring strategies that promote diversity within academic medicine mentoring programs. Methods: Studies were identified by searching Medline using MESH terms for mentoring and academic medicine. Eligibility criteria included studies focused on junior faculty in research-focused positions, receiving mentorship, in an academic medical center in the USA, with outcomes collected to measure career success (career trajectory, career satisfaction, quality of life, research productivity, leadership positions). Data were abstracted using a standardized data collection form, and best practices were summarized. Results: Search terms resulted in 1,842 articles for title and abstract review, with 27 manuscripts meeting inclusion criteria. Two studies focused specifically on women, and four studies focused on junior faculty from racial/ethnic backgrounds underrepresented in medicine. From the initial search, few studies were designed to specifically increase diversity or capture outcomes relevant to promotion within academic medicine. Of those which did, most studies captured the impact on research productivity and career satisfaction. Traditional one-on-one mentorship, structured peer mentorship facilitated by a senior mentor, and peer mentorship in combination with one-on-one mentorship were found to be effective strategies to facilitate research productivity. Conclusion: Efforts are needed at the mentee, mentor, and institutional level to provide mentorship to diverse junior faculty on research competencies and career trajectory, create a sense of belonging, and connect junior faculty with institutional resources to support career success.

The Effectiveness of Sarcopenia Interventions for Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Among people with cancer undergoing chemotherapy, generalized loss of muscle mass, termed secondary sarcopenia , is associated with treatment toxicities and physical disability. OBJECTIVE: This systematic review and meta-analysis aimed to provide an overview of current interventions for sarcopenia in cancer patients receiving chemotherapy and to assess potentially effective interventions. METHODS: We searched PubMed, Scopus, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus, and EMBASE for primary original research of exercise and nutrition interventions for sarcopenia published in English. The review used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Standardized mean difference and 95% confidence interval (CI) were calculated as effect measures by applying the random-effects model. RESULTS: The 6 included studies showed a trend toward significantly increasing skeletal muscle mass after intervention (mean difference, 0.168; 95% CI, -0.015 to 0.352; P = .072), with no significant changes in lean body mass loss after intervention (mean difference, -0.014; 95% CI, -1.291 to 1.264; P = .983). Resistance exercise and combined exercise and nutrition intervention were more effective at preserving or increasing muscle mass. CONCLUSIONS: Early implementation of a resistance exercise intervention or a combined exercise and nutrition intervention is a promising strategy for avoiding muscle mass loss during chemotherapy. Additional evidence-based assessments of interventions for secondary sarcopenia are needed to identify the most effective approach. IMPLICATIONS FOR PRACTICE: In clinical practice, oncology nurses should frequently assess cancer patients' muscle mass and when warranted should implement the most feasible early sarcopenia intervention to minimize the adverse outcomes of this condition.

Advancing diversity, equity, and inclusion within clinical and translational science training programs: A qualitative content analysis of the training breakout session at the national CTSA program meeting.

Background: Diversity, equity, and inclusion (DEI) in clinical and translational science (CTS) are paramount to driving innovation and increasing health equity. One important area for improving diversity is among trainees in CTS programs. This paper reports on findings from a special session at the November 2020 Clinical and Translational Science Award (CTSA) national program meeting that focused on advancing diversity and inclusion within CTS training programs. Methods: Using qualitative content analysis, we identified approaches brought forth to increase DEI in KL2 career development and other training programs aimed at early-stage CTS investigators, beyond the six strategies put forth to guide the breakout session (prioritizing representation, building partnerships, making it personal, designing program structure, improving through feedback, and winning endorsement). We used an inductive qualitative content analysis approach to identify themes from a transcript of the panel of KL2 program leaders centered on DEI in training programs. Results: We identified four themes for advancing DEI within CTS training programs: 1) institutional buy-in; 2) proactive recruitment efforts; 3) an equitable application process; and 4) high-quality, diverse mentorship. Conclusion: Implementing these strategies in CTS and other training programs will be an important step for advancing DEI. However, processes need to be established to evaluate the implementation and effectiveness of these strategies through continuous quality improvement, a key component of the CTSA program. Training programs within the CTSA are well-positioned to be leaders in this critical effort to increase the diversity of the scientific workforce.

The effects of COVID-19 on respiratory muscle performance: making the case for respiratory muscle testing and training.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in multiorgan damage primarily mediated by viral infiltration via angiotensin-converting enzyme-2 receptors on the surface of cells. A primary symptom for many patients is exertional dyspnoea which may persist even beyond recovery from the viral infection. Respiratory muscle (RM) performance was hypothesised as a contributing factor to the severity of coronavirus disease 2019 (COVID-19) symptoms, such as dyspnoea, and outcomes. This was attributed to similarities between patient populations at elevated risk for severe COVID-19 symptoms and those with a greater likelihood of baseline RM weakness and the effects of prolonged mechanical ventilation. More recent evidence suggests that SARS-CoV-2 infection itself may cause damage to the RM, and many patients who have recovered report persistent dyspnoea despite having mild cases, normal lung function or undamaged lung parenchyma. These more recent findings suggest that the role of RM in the persistent dyspnoea due to COVID-19 may be more substantial than originally hypothesised. Therefore, screening for RM weakness and providing interventions to improve RM performance appears to be important for patients with COVID-19. This article will review the impact of SARS-CoV-2 infection on RM performance and provide clinical recommendations for screening RM performance and treatment interventions.

Hemispheric lateralization, endothelial function, and arterial compliance in chronic post-stroke individuals: A cross-sectional exploratory study.

Purpose/Aim: Cardiovascular function is controlled and regulated by a functional brain-heart axis. Although the exact mechanism is not fully understood, several studies suggest a hemispheric asymmetry in the neural control of cardiovascular function. Thus, the purpose of this study was to examine whether endothelial function and arterial compliance differ between individuals with left- and right-sided strokes.Materials and Methods: This was a cross-sectional exploratory study. Thirty individuals more than 6 months after stroke participated in the study. The endothelial function was assessed by ultrasound-measured flow-mediated dilation of the nonparetic arm brachial artery (baFMD). The arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central aortic pulse wave analysis [augmentation index (AIx), augmentation index normalized to a heart rate of 75 bpm (AIx@75) and reflection magnitude (RM)] using applanation tonometry. Results: Participants with right-sided stroke had worse endothelial function than those with left-sided stroke. This difference (baFMD = 2.51%) was significant (p = 0.037), and it represented a medium effect size (r = 0.38). Likewise, they had higher arterial stiffness than those with left-sided stroke. This difference (AIx = 10%; RM = 7%) was significant (p = 0.011; p = 0.012), and it represented a medium effect size (r = 0.48; r = 0.47).Conclusions: Our findings suggest that individuals with right-sided stroke have reduced endothelial function and arterial compliance compared to those with left-sided stroke. These data may indicate that those with right-sided strokes are more susceptible to cardiovascular events.

DNA Hypomethylation as a Potential Link between Excessive Alcohol Intake and Cardiometabolic Dysfunction in Morbidly Obese Adults.

A large percentage of obese patients in the United States suffer a comorbid substance use disorder, mainly alcohol use. Alcohol consumption interferes with the absorption of dietary methyl donors such as folate required for the one-carbon metabolism pathway and subsequently for DNA methylation. In this study, we assessed the association between alcohol consumption and DNA methylation in obese subjects. We obtained visceral adipose tissue (VAT) biopsies from bariatric patients. DNA methylation of 94 genes implicated in inflammation and immunity were analyzed in VAT in relation to alcohol consumption data obtained via questionnaires. Vasoreactivity was measured in the brachial artery and the VAT-isolated arterioles. Pro-inflammatory genes were significantly hypomethylated in the heavy drinking category correlating with higher levels of circulating inflammatory cytokines. Alcohol consumption correlated positively with body mass index (BMI), fat percentage, insulin resistance, impaired lipid profile, and systemic inflammation and negatively with plasma folate and vitamin B12, inflammatory gene DNA methylation, and vasoreactivity. In conclusion, these data suggest that alcohol intake is associated with lower DNA methylation and higher inflammation and cardiometabolic risk in obese individuals.

Alcohol Consumption: A New Risk Factor for Arterial Stiffness?

The relationship between alcohol consumption and cardiovascular disease risk is complex. Low-to-moderate daily alcohol consumption (1-2 drinks/day) is associated with reduced risk, whereas greater amounts of alcohol consumption and a "binge" pattern of drinking are associated with increased cardiovascular risk and mortality. Arterial stiffness may help explain the complex relationship. This integrated review summarizes data from studies examining the associations between alcohol consumption and pulse wave velocity, a gold standard measure of arterial stiffness. We also briefly review the concept and methodology of pulse wave velocity measurement as well as the mechanisms of alcohol-induced arterial stiffening. Findings among the different studies reviewed were inconsistent with methodological challenges related to alcohol use assessment. While making specific conclusions regarding this relationship is tenuous; the data suggest that excessive alcohol consumption or a binge drinking pattern is associated with increased arterial stiffness.

Effects of Exercise Mode on Improving Cardiovascular Function and Cardiorespiratory Fitness After Bariatric Surgery: A Narrative Review.

ABSTRACT: Obesity affects 600 million people globally and increases the risk of developing cardiovascular disease, stroke, diabetes, and cancer. Bariatric surgery is an increasingly popular therapeutic intervention for morbid obesity to induce rapid weight loss and reduce obesity-related comorbidities. However, some bariatric surgery patients, after what is considered a successful surgical procedure, continue to manifest obesity-related health issues, including weight gain, reduced physical function, persistent elevations in blood pressure, and reduced cardiorespiratory fitness. Cardiorespiratory fitness is a strong predictor of mortality and several health outcomes and could be improved by an appropriate exercise prescription after bariatric surgery. This review provides a broad overview of exercise training for patients after bariatric surgery and discusses cardiorespiratory fitness and other potential physiological adaptations in response to exercise training.

Efeitos do treinamento intervalado de alta intensidade e do treinamento combinado associado à terapia de fotobiomodulação em pacientes diabéticos do tipo 2 (DT2): protocolo para um estudo controlado randomizado / Effects of high-intensity interval training and combined training associated with photobiomodulation therapy in type 2 diabetic (T2D) patients: a protocol for a randomized controlled trial

INTRODUÇÃO: O diabetes tipo 2 (DT2) pode ser responsável por disfunção cardiometabólica e redução da qualidade de vida (QV) devido ao seu impacto negativo na capacidade funcional de exercício. OBJETIVO: Investigar os efeitos de diferentes tipos de treinamento físico [treinamento intervalado de alta intensidade (TIAI) e treinamento combinado (TC)] associado à terapia com diodo emissor de luz (LED) no status cardiometabólico, capacidade funcional e QV em pacientes com DT2. MÉTODOS: Estudo controlado randomizado que será realizado em laboratório universitário de reabilitação cardiopulmonar com pessoas da comunidade com diagnóstico confirmado de DT2, idade ≥ 18 anos e sedentários nos últimos seis meses. Os participantes serão alocados aleatoriamente para um dos seis grupos: TIAI com e sem terapia LED, TC com e sem terapia LED, grupo controle com e sem terapia LED. O protocolo de treinamento deve ser realizado por 12 semanas, 3 vezes na semana em dias alternados, totalizando 36 sessões de treinamento. O desfecho primário será a capacidade de exercício e o controle glicêmico. Os desfechos secundários serão QV, função endotelial, função musculoesquelética, modulação autonômica cardíaca e composição corporal. Os resultados serão medidos antes e após 12 semanas de treinamento. Para análise estatística será utilizado o programa SPSS® 19.0. O nível de significância adotado será p<0,05. PERSPECTIVAS: Os resultados deste estudo têm o potencial de fornecer informações importantes sobre os efeitos de diferentes tipos de treinamento físico associados à terapia com LED e podem apoiar o uso dessa combinação terapêutica em pacientes com DT2, melhorando sua saúde geral.

INTRODUCTION: Type 2 diabetes (T2D) can be responsible for significant cardiometabolic dysfunction and reduction in quality of life (QOL) due to its negative impact on functional exercise capacity. OBJECTIVE: To investigate the effects of different modes of physical training (high-intensity interval training [HIIT] and combined training [CT]) associated with light-emitting diode (LED) therapy on the cardiometabolic status, functional capacity, and quality of life (QOL) in T2D patients. METHODS: A randomized controlled trial will be conducted in a university cardiopulmonary rehabilitation laboratory; the participants will be community-dwelling people with a confirmed diagnosis of T2D, aged ≥ 18 years, and with a sedentary lifestyle in the last six months. They will be randomly allocated to one of six groups: TIAI with and without LED therapy, CT with and without LED therapy, and a control group with and without LED therapy. The training protocol will be performed for 12 weeks, three times a week on alternate days, with a total of 36 training sessions. The primary outcomes will be functional exercise capacity and glycemic control. The secondary outcomes will be QOL, endothelial function, musculoskeletal function, autonomic nervous system modulation, and body composition. The outcomes will be measured before and after 12 weeks of training. SPSS® 19.0 software will be used for statistical analysis. The significance level is set at P <0.05. PERSPECTIVES: The findings of this trial have the potential to provide important insights into the effects of different modes of physical training associated with LED therapy and may support the use of this therapy combination in T2D patients, which may improve their general health.

Differential effects of obesity on visceral versus subcutaneous adipose arteries: role of shear-activated Kir2.1 and alterations to the glycocalyx.

Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAAs), but not subcutaneous adipose arteries (SAAs), exhibit endothelial dysfunction. To determine whether differences in SAA versus VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx, mice were fed a normal rodent diet, or a high-fat Western diet to induce obesity. Flow-induced vasodilation (FIV) was measured ex vivo. Functional downregulation of endothelial Kir2.1 was accomplished by transducing adipose arteries from mice and obese humans with adenovirus containing a dominant-negative Kir2.1 construct. Kir function was tested in freshly isolated endothelial cells seeded in a flow chamber for electrophysiological recordings under fluid shear. Atomic force microscopy was used to assess biophysical properties of the glycocalyx. Endothelial dysfunction was observed in VAAs of obese mice and humans. Downregulating Kir2.1 blunted FIV in SAAs, but had no effect on VAAs, from obese mice and humans. Obesity abolished Kir shear sensitivity in VAA endothelial cells and significantly altered the VAA glycocalyx. In contrast, Kir shear sensitivity was observed in SAA endothelial cells from obese mice and effects on SAA glycocalyx were less pronounced. We reveal distinct differences in Kir function and alterations to the glycocalyx that we propose contribute to the dichotomy in SAA versus VAA endothelial function with obesity.NEW & NOTEWORTHY We identified a role for endothelial Kir2.1 in the differences observed in VAA versus SAA endothelial function with obesity. The endothelial glycocalyx, a regulator of Kir activation by shear, is unequally perturbed in VAAs as compared with SAAs, which we propose results in a near complete loss of VAA endothelial Kir shear sensitivity and endothelial dysfunction. We propose that these differences underly the preserved endothelial function of SAA in obese mice and humans.

Longitudinal physical performance and blood pressure changes in older women: Findings form the women's health initiative.

BACKGROUND: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. METHODS: 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65-69 y; 70-79 y). RESULTS: Overall, each z-score unit increment in grip strength was associated with 0.59 mmHg (95% CI 0.10, 1.08) higher SBP, and 0.39 mmHg (95% CI 0.11, 0.67) higher DBP. In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.81; 95% CI 0.23-1.39), among antihypertensive medication users (0.93; 95% CI 0.44, 1.41) and non-users (0.37; 95% CI 0.03, 0.71), and in those aged 65-69 y (0.64; 95% CI 0.04, 1.24). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70-79 y. Associations between any performance measure and pulse pressure change were not significant. CONCLUSION: These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age.