Relation between frailty and hypertension is partially mediated by physical activity among males and females in the Canadian Longitudinal Study on Aging.

Frailty reflects the heterogeneity in aging and may lead to the development of hypertension and heart disease, but the frailty-cardiovascular relationship and whether physical activity modifies this relationship in males and females are unclear. We tested whether higher frailty was positively associated with hypertension and heart disease in males and females and whether habitual movement mediated this relationship. The relationship between baseline frailty with follow-up hypertension and heart disease was investigated using the Canadian Longitudinal Study on Aging at 3-year follow-up data (males: n = 13,095; females: n = 13,601). Frailty at baseline was determined via a 73-item deficit-based index, activity at follow-up was determined via the Physical Activity Scale for the Elderly, and cardiovascular function was self-reported. Higher baseline frailty level was associated with a greater likelihood of hypertension and heart disease at follow-up, with covariate-adjusted odds ratios of 1.08-1.09 (all, P < 0.001) for a 0.01 increase in frailty index score. Among males and females, sitting time and strenuous physical activity were independently associated with hypertension, with these activity behaviors being partial mediators (except male-sitting time) for the frailty-hypertension relationship (explained 5-10% of relationship). The strength of this relationship was stronger among females. Only light-moderate activity partially mediated the relationship (∼6%) between frailty and heart disease in females, but no activity measure was a mediator for males. Higher frailty levels were associated with a greater incidence of hypertension and heart disease, and strategies that target increases in physical activity and reducing sitting may partially uncouple this relationship with hypertension, particularly among females.NEW & NOTEWORTHY Longitudinally, our study demonstrates that higher baseline frailty levels are associated with an increased risk of hypertension and heart disease in a large sample of Canadian males and females. Movement partially mediated this relationship, particularly among females.

Sympathetic determinants of resting blood pressure in males and females.

Discharge of postganglionic muscle sympathetic nerve activity (MSNA) is related poorly to blood pressure (BP) in adults. Whether neural measurements beyond the prevailing level of MSNA can account for interindividual differences in BP remains unclear. The current study sought to evaluate the relative contributions of sympathetic-BP transduction and sympathetic baroreflex gain on resting BP in young adults. Data were analyzed from 191 (77 females) young adults (18-39 years) who underwent continuous measurement of beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and fibular nerve MSNA (microneurography). Linear regression analyses were computed to determine associations between sympathetic-BP transduction (signal-averaging) or sympathetic baroreflex gain (threshold technique) and resting BP, before and after controlling for age, body mass index, and MSNA burst frequency. K-mean clustering was used to explore sympathetic phenotypes of BP control and consequential influence on resting BP. Sympathetic-BP transduction was unrelated to BP in males or females (both R2 < 0.01; P > 0.67). Sympathetic baroreflex gain was positively associated with BP in males (R2 = 0.09, P < 0.01), but not in females (R2 < 0.01; P = 0.80), before and after controlling for age, body mass index, and MSNA burst frequency. K-means clustering identified a subset of participants with average resting MSNA, yet lower sympathetic-BP transduction and lower sympathetic baroreflex gain. This distinct subgroup presented with elevated BP in males (P < 0.02), but not in females (P = 0.10). Sympathetic-BP transduction is unrelated to resting BP, while the association between sympathetic baroreflex gain and resting BP in males reveals important sex differences in the sympathetic determination of resting BP.NEW & NOTEWORTHY In a sample of 191 normotensive young adults, we confirm that resting muscle sympathetic nerve activity is a poor predictor of resting blood pressure and now demonstrate that sympathetic baroreflex gain is associated with resting blood pressure in males but not females. In contrast, signal-averaged measures of sympathetic-blood pressure transduction are unrelated to resting blood pressure. These findings highlight sex differences in the neural regulation of blood pressure.

Sitting knee-flexion angle does not influence endothelial-dependent vasodilation in laboratory or free-living conditions.

INTRODUCTION: Single bouts of prolonged bent-legged sitting attenuate popliteal endothelial-dependent vasodilation (as assessed via flow-mediated dilation [FMD]), which is partially attributed to arterial 'kinking'. However, the impact of knee-flexion angle on sitting-induced popliteal FMD is unknown. The objective of this study was to perform separate laboratory and free-living studies to test the hypotheses that: (1) popliteal FMD impairments would be graded between knee flexions at 90° (bent-legged sitting) > 45° > 0° (straight-legged sitting) following a 3-hour bout of sitting; and (2) more habitual time spent bent-legged sitting (< 45°) would be associated with lower FMD. METHODS: The laboratory study included eight young, healthy adults (24 ± 2 years; four women) who underwent two sitting bouts over 2 days with one leg positioned at a knee-flexion angle of 0° or 90° and the opposite leg at 45° knee flexion. Popliteal FMD was assessed at pre- and postsitting timepoints. RESULTS: Sitting-induced reductions in FMD were similar between all knee-flexion angles (all, p > 0.674). The free-living study included 35 young, healthy adults (23 ± 3 years; 16 women) who wore three activPAL monitors (torso, thigh, shin) to determine detailed sedentary postures. Time spent sedentary (624 ± 127 min/day), straight-legged sitting (112 ± 98 min/day), and bent-legged sitting (442 ± 106 min/day) were not related to relative FMD (5.3 ± 1.8%; all, p > 0.240). CONCLUSION: These findings suggest that knee-flexion angle-mediated arterial 'kinking' during sitting is not a major contributor toward sitting-induced popliteal endothelial-dependent vasodilatory dysfunction.

Development and validation of a frailty index for use in the osteoarthritis initiative.

BACKGROUND: The Osteoarthritis Initiative (OAI) evaluates the development and progression of osteoarthritis. Frailty captures the heterogeneity in aging. Use of this resource-intensive dataset to answer aging-related research questions could be enhanced by a frailty measure. OBJECTIVE: To: (i) develop a deficit accumulation frailty index (FI) for the OAI; (ii) examine its relationship with age and compare between sexes, (iii) validate the FI versus all-cause mortality and (iv) compare this association with mortality with a modified frailty phenotype. DESIGN: OAI cohort study. SETTING: North America. SUBJECTS: An FI was determined for 4,755/4,796 and 4,149/4,796 who had a valid FI and frailty phenotype. METHODS: Fifty-nine-variables were screened for inclusion. Multivariate Cox regression evaluated the impact of FI or phenotype on all-cause mortality at follow-up (up to 146 months), controlling for age and sex. RESULTS: Thirty-one items were included. FI scores (0.16 ± 0.09) were higher in older adults and among females (both, P < 0.001). By follow-up, 264 people had died (6.4%). Older age, being male, and greater FI were associated with a higher risk of all-cause mortality (all, P < 0.001). The model including FI was a better fit than the model including the phenotype (AIC: 4,167 vs. 4,178) and was a better predictor of all-cause mortality than the phenotype with an area under receiver operating characteristic curve: 0.652 vs. 0.581. CONCLUSION: We developed an FI using the OAI and validated it in relation to all-cause mortality. The FI may be used to study aging on clinical, functional and structural aspects of osteoarthritis included in the OAI.

Effectiveness of contrast-enhanced duplex ultrasound for detecting renal artery stenosis: A systematic review.

PURPOSE: Contrast-enhanced duplex ultrasound (CEUS) might be a useful tool to diagnosing renal artery stenosis (RAS). We amalgamated and reviewed the evidence assessing the diagnostic accuracy of CEUS on detecting RAS compared to angiography. METHODS: This preregistered systematic review included studies that compared the presence of RAS via CEUS with angiography. Sources were searched in November 2022 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier (n = 1717). The Quality Assessment of Diagnostic Studies 2 tool assessed study quality. Results are presented narratively. RESULTS: The studies included (n = 11) had a total of 447 unique participants (193 females) and average age of 56 ± 9 years. Five of eleven studies investigated CEUS using SonoVue contrast agent and reported an average accuracy (91% ± 2%), sensitivity (91% ± 3%), specificity (90% ± 5%), negative predictive value (86% ± 6%), and positive predictive value (94% ± 1%) with all values >80%. The accuracy of CEUS using other types of contrast agent (n = 6), including Levovsit (n = 3/6), Definity (n = 1/6), perfienapent emulsion (n = 1/6), and perfluorocarbon-exposed sonicated dextrose albumin (n = 1/6) was mixed. These studies detected an average accuracy of 91 ± 11% (n = 2/3% > 80%), sensitivity of 98% ± 4%, (n = 3/3% > 80%), and specificity of 86% ± 10% (n = 2/3% > 80%). Included studies had generally low risk of bias and applicability concerns except for unclear flow and timing (n = 7/11) and applicability of patient selection (n = 4/11). CONCLUSION: Despite being limited by the heterogeneity of included studies, our review indicates a high overall diagnostic accuracy for CEUS to detect RAS compared to angiography, with the largest evidence-base for SonoVue contrast. Radiologists and hospital decision makers should consider CEUS as an acceptable alternative to angiography.

Impact of exercise training on pulse wave velocity in healthy and clinical populations: a systematic review of systematic reviews.

Elevated pulse wave velocity (PWV) determined arterial stiffness is a prominent marker of cardiovascular disease (CVD) risk. Exercise training delays the progression of CVD, but existing reviews on the impact of training on PWV are conflicting. We synthesized the evidence on the effects of exercise training interventions on PWV. We searched Scopus, EMBASE, PubMed, CINAHL, and Academic Search Premier databases for systematic reviews including PWV, and examined the effects of exercise training on PWV. We screened 842 citations that resulted in 44 systematic reviews, including 22 meta-analyses [unique participants, n = 6,719 (3,390 females)]. Studies were conducted in general adults with/without disease(s) (n = 19, 8 meta-analyses), kidney disease (n = 9, 6 meta-analyses), increased CVD risk or CVD (n = 7, 5 meta-analyses), type 2 diabetes mellitus (n = 3, 2 meta-analyses), and other conditions (n = 6, 2 meta-analyses). In general adults, PWV was reduced by aerobic exercise (ß, -0.75 to -0.52 m/s) and low-to-moderate intensity resistance exercise training (ß, -0.34 m/s). Exercise training was beneficial for patients with kidney disease (ß, -1.13 to -0.56 m/s). Aerobic exercise improved PWV in adults with CVD or high CVD risk (ß, -0.70 to -0.42 m/s). Combined aerobic and resistance exercise training decreased carotid-femoral (CF) PWV in patients with CVD (ß, -1.15 m/s) and decreased brachial-ankle (BA) PWV in postmenopausal females (ß, -1.18 m/s). Neither aerobic nor combined training improved PWV in individuals with type 2 diabetes. The potential physiological mechanisms involved are discussed. Overall, the included systematic reviews and meta-analyses documented that exercise training was an effective strategy to improve PWV, but the optimal type of training varied between populations.

Interrupting bedtime to reverse frailty levels in acute care: a study protocol for the Breaking Bad Rest randomized controlled trial.

BACKGROUND: Hospitalized older patients spend most of the waking hours in bed, even if they can walk independently. Excessive bedrest contributes to the development of frailty and worse hospital outcomes. We describe the study protocol for the Breaking Bad Rest Study, a randomized clinical trial aimed to promoting more movement in acute care using a novel device-based approach that could mitigate the impact of too much bedrest on frailty. METHODS: Fifty patients in a geriatric unit will be randomized into an intervention or usual care control group. Both groups will be equipped with an activPAL (a measure of posture) and StepWatch (a measure of step counts) to wear throughout their entire hospital stay to capture their physical activity levels and posture. Frailty will be assessed via a multi-item questionnaire assessing health deficits at admission, weekly for the first month, then monthly thereafter, and at 1-month post-discharge. Secondary measures including geriatric assessments, cognitive function, falls, and hospital re-admissions will be assessed. Mixed models for repeated measures will determine whether daily activity differed between groups, changed over the course of their hospital stay, and impacted frailty levels. DISCUSSION: This randomized clinical trial will add to the evidence base on addressing frailty in older adults in acute care settings through a devices-based movement intervention. The findings of this trial may inform guidelines for limiting time spent sedentary or in bed during a patient's stay in geriatric units, with the intention of scaling up this study model to other acute care sites if successful. TRIAL REGISTRATION: The protocol has been registered at clinicaltrials.gov (identifier: NCT03682523).

Mechanistic, participant, and movement-related factors that contribute to low-flow-mediated constriction.

Endothelial function is commonly determined via the ultrasound-based flow-mediated dilation (FMD) technique which assesses arterial dilation in response to a hyperemia response following distal cuff occlusion. However, the low-flow-mediated constriction (L-FMC) response during cuff-induced ischemia is often overlooked. L-FMC provides unique information regarding endothelial function, but vascular researchers may be unclear on what this metric adds. Therefore, the objective of this review was to examine the mechanistic determinants and participant-level factors of L-FMC. Existing mechanistic studies have demonstrated that vasoreactivity to low flow may be mediated via non-nitric oxide vasodilators (i.e., endothelial hyperpolarizing factors and/or prostaglandins), inflammatory markers, and enhancement of vasoconstriction via endothelin-1. In general, participant-level factors such as aging and presence of cardiovascular conditions generally are associated with attenuated L-FMC responses. However, the influence of sex on L-FMC is unclear with divergent results between L-FMC in upper versus lower limb vessels. The ability of aerobic exercise to augment L-FMC (i.e., make more negative) is well supported, but there is a major gap in the literature concerning the mechanistic underpinnings of this observation. This review summarizes that while larger L-FMC responses are generally healthy, the impact of interventions to augment/attenuate L-FMC has not included mechanistic measures that would provide insight into non-nitric oxide-based endothelial function. Clarifications to terminology and areas of further inquiry as it relates to the specific pharmacological, individual-level factors, and lifestyle behaviors that impact L-FMC are highlighted. A greater integration of mechanistic work alongside applied lifestyle interventions is required to better understand endothelial cell function to reductions in local blood flow.

Sex-specific frailty and chronological age normative carotid artery intima-media thickness values using the Canadian longitudinal study of aging.

OBJECTIVES: Carotid intima-media-thickness (cIMT) is predictive of future cardiovascular events, increases with chronological age, and greater in males. The accumulation of health deficits (or frailty) is a marker of biological age. However, normative cIMT values are lacking and would be an important comparative tool for healthcare providers and researchers. This study aimed to establish sex-specific normative cIMT values across chronological age and frailty levels (i.e. biological age). METHODS: Frailty and right common cIMT data were extracted from the Canadian Longitudinal Study of Aging baseline comprehensive cohort of middle-aged and older adults (n = 10,209; 5000 females). cIMT was assessed via high-resolution ultrasound. Frailty was determined using a 52-item frailty index. Ordinary least squares and quantile regressions were conducted between age (years or frailty index) with cIMT (average or maximum), separately for males and females. RESULTS: In both sexes, average and maximum cIMT increased with higher chronological age and frailty. Both cIMT metrics increased non-linearly (quadratic-cIMT term) with advancing age (ß-coefficients for quadratic and linear terms: all, p < 0.001), except for the linear relationship between average and maximum cIMT with chronological age among males (p < 0.001). Sex-specific normative average and maximum cIMT values were established (1st-99th percentiles, 5% increments), separately for chronological and biological ages. CONCLUSIONS: This is the largest sample of adults to establish normative cIMT outcomes that includes older adults. The chronological age and frailty-related normative cIMT outcomes will serve as a useful resource for healthcare professionals and researchers to establish "normal" age- and sex-specific cIMT values.

Characterization of Detailed Sedentary Postures Using a Tri-Monitor ActivPAL Configuration in Free-Living Conditions.

Objective monitors such as the activPAL characterize time when the thigh is horizontal as sedentary time. However, there are physiological differences between lying, bent-legged sitting, and straight-legged sitting. We introduce a three-monitor configuration to assess detailed sedentary postures and demonstrate its use in characterizing such positions in free-living conditions. We explored time spent in each sedentary posture between prolonged (>1 h) versus non-prolonged (<1 h) sedentary bouts. In total, 35 healthy adults (16♀, 24 ± 3 years; 24 h/day for 6.8 ± 1.0 days) wore an activPAL accelerometer on their thigh, torso, and shin. Hip and knee joint flexion angle estimates were determined during sedentary bouts using the dot-product method between the torso−thigh and thigh−shin, respectively. Compared to lying (69 ± 60 min/day) or straight-legged sitting (113 ± 100 min/day), most time was spent in bent-legged sitting (439 ± 101 min/day, p < 0.001). Most of the bent-legged sitting time was accumulated in non-prolonged bouts (328 ± 83 vs. 112 ± 63 min/day, p < 0.001). In contrast, similar time was spent in straight-legged sitting and lying between prolonged/non-prolonged bouts (both, p > 0.26). We document that a considerable amount of waking time is accumulated in lying or straight-legged sitting. This methodological approach equips researchers with a means of characterizing detailed sedentary postures in uncontrolled conditions and may help answer novel research questions on sedentariness.

Is "not different" enough to conclude similar cardiovascular responses across sexes?

The number of research studies investigating whether similar or different cardiovascular responses or adaptations exist between males and females is increasing. Traditionally, difference-based statistical methods, e.g., t test, ANOVA, etc., have been implemented to compare cardiovascular function between males and females, with a P value of >0.05 used to denote similarity between sexes. However, an absence of evidence, i.e., large P value, is not evidence of absence, i.e., no sex differences. Equivalence testing determines whether two measures or groups provide statistically equivalent outcomes, in that they differ by less than an "ideally prespecified" smallest effect size of interest. Our perspective discusses the applicability and utility of integrating equivalence testing when conducting sex comparisons in cardiovascular research. An emphasis is placed on how cardiovascular researchers may conduct equivalence testing across multiple study designs, e.g., cross-sectional comparisons, repeated-measures intervention, etc. The strengths and weaknesses of this statistical tool are discussed. Equivalence analyses are relatively simple to conduct, may be used in conjunction with traditional hypothesis testing to interpret findings, and permit the determination of statistically equivalent responses between sexes. We recommend that cardiovascular researchers consider implementing equivalence testing to better our understanding of similar and different cardiovascular processes between sexes.

What is the impact of aerobic fitness and movement interventions on low-flow-mediated vasoconstriction? A systematic review of observational and intervention studies.

The cardiovascular benefits of physical exercise are well established. The vasoreactivity that occurs during reductions in local arterial blood flow, termed low-flow-mediated constriction (L-FMC), is a measure of endothelial-dependent vasoconstrictor function. It is unclear whether aerobic fitness and movement (or lack thereof) influences L-FMC. We systematically reviewed studies examining the impact of physical behaviours on L-FMC. To be included, cross-sectional and interventional studies had to examine the impact of a physical behaviour on L-FMC in adults. There were no language or date of publication restrictions. Sources were searched in May, 2021 and included Scopus, Embase, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. Fourteen studies (15 arms; 313 participants; 398 total observations from four arteries) met the inclusion criteria. The study quality varied from four out of 14 (controlled intervention scoring) to nine out of 12 (longitudinal intervention with no control group scoring) with the total points dependent upon the study design. Conflicting results were reported for acute prolonged sitting studies (attenuated L-FMC: n = 1; no change: n = 1) and resistance exercise (increased L-FMC: n = 2; no change: n = 2). Most observational studies examining aerobic fitness (3/4 studies) and aerobic exercise interventions (4/5 studies) observed a favourable effect on L-FMC. Overall, the included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses. Our systematic review highlights the heterogeneity between studies and identifies current gaps and future directions to better our understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function. PROSPERO Registration No.: CRD42021248241.

Impact of habitual sedentary patterns on popliteal artery endothelial-dependent vasodilation in healthy adults.

INTRODUCTION: Acute, laboratory-based bouts of prolonged sitting attenuate lower-limb arterial endothelial-dependent vasodilation. However, the impact of habitual sedentary patterns on popliteal artery endothelial health is unclear. We tested the hypothesis that greater habitual total sedentary time, more time spent in prolonged sedentary bouts, and fewer sedentary breaks would be associated with worse popliteal flow-mediated dilation (FMD) responses. METHODS: This cross-sectional study used 98 healthy participants (19-77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD. Both relative (%baseline diameter) and absolute (mm) FMD were calculated. Using bivariate correlation and multiple regression analyses, we examined if there were relationships between sedentary outcomes and FMD while statistically controlling for any potential confounders. RESULTS: In the multiple regression model, age (p = 0.006, ß = -0.030, 95% CI = -0.051, -0.009) and total time in sedentary bouts > 1 hour (p = 0.031, ß = -0.005, 95% CI = -0.009, -0.001) were independent predictors of relative FMD. Age (ß = -0.002, 95% CI = -0.003, -0.001), mean blood flow (ß = 0.013, 95% CI = 0.002, 0.024), moderate-intensity physical activity (ß = 155.9E-5, 95% CI = 22.4E-5, 289.4E-5), sedentary breaks (ß = 0.036, 95% CI = 0.007, 0.066), and total time spent in sedentary bouts > 1 hour (ß = -25.02E-5, 95% CI = -47.67E-5, -2.378E-5) were predictors of absolute FMD (all, p < 0.047). All independent outcomes remained significant after partially controlling for all other predictor variables (all, p < 0.031). CONCLUSIONS: Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function. The patterns by which sedentary time is accumulated may be more important than the total sedentary time on lower-limb arterial health.

Comparison of signal-averaging and regression approaches to analyzing sympathetic transduction.

PURPOSE: Spontaneous sympathetic transduction reflects the vascular and/or pressor responses to bursts of muscle sympathetic nerve activity (MSNA). Separately, signal-averaging and regression-based approaches have been implemented to quantify resting sympathetic transduction. It is unknown whether the outcomes of these analytical approaches provide (dis)similar information, which is imperative for between-study comparisons and the amalgamation of results for synthesis of multiple studies (i.e., meta-analyses). We explored the diastolic blood pressure (DBP) responses to spontaneous bursts of MSNA between these two methods of analysis. METHODS: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 52 healthy, normotensive adults (age 38 ± 20 years; 19 females). For the signal-averaged method, transduction was quantified as the mean peak increase in DBP (ΔDBP) during the 12 cardiac cycles following each MSNA burst. In addition, DBP was regressed to a moving two-cardiac-cycle window of normalized relative burst height (mmHg/relative %) to provide the regression-based transduction outcome. RESULTS: The signal-averaged (1.2 ± 0.7 mmHg) and regression-based approaches (0.009 ± 0.016 mmHg/%) were unrelated (ρ = 0.03, p = 0.86). Adding to the discrepancy, only the signal-averaging approach demonstrated a lower transduction in middle-aged-older males versus younger males. CONCLUSIONS: The decision of which method to use when calculating sympathetic transduction influences study outcomes, with the two most common methods of determining transduction being unrelated. There are challenges of making sweeping conclusions across studies if different analysis strategies are implemented. An understanding of when to use each method is needed to adopt a harmonized approach to quantifying sympathetic transduction.

Physical Activity Counselling and Exercise Prescription Practices among Dietitians Across Nova Scotia.

The purpose of this study was to assess the perceptions and practices around physical activity counselling and exercise prescription of dietitians in Nova Scotia. Dietitians (n = 95) across Nova Scotia completed an online self-reflection survey regarding their current physical activity and exercise (PAE) practices. Most (51%; n = 48) reported no previous PAE educational training. Dietitians infrequently prescribed exercise to their patients (16% ± 26% of appointments) or provided PAE referrals (17% ± 24%). Dietitians reported moderate confidence (57% ± 21%) performing PAE counselling and included PAE-related content in half of patient appointments (52% ± 31%). Almost all respondents (95%) identified interest in further PAE education or training. Open-ended responses also demonstrated the need for community-based exercise programs (28% of providers) and qualified exercise professionals to refer to (25%). Overall, dietitians report rarely providing patients with written exercise prescriptions or referrals to other professionals for PAE content but do frequently include PAE in patient appointments. Dietitians in Nova Scotia are well positioned to promote PAE, but more educational training and improved referral systems to qualified exercise professionals or community exercise programs is strongly desired. Exercise professionals and dietitians should concurrently advocate for these changes and collaborate to help more patients lead physically active lifestyles.

An open-source program to analyze spontaneous sympathetic neurohemodynamic transduction.

The sympathetic nervous system is important for the beat-by-beat regulation of arterial blood pressure and the control of blood flow to various organs. Microneurographic recordings of pulse-synchronous muscle sympathetic nerve activity (MSNA) are used by numerous laboratories worldwide. The transduction of hemodynamic and vascular responses elicited by spontaneous bursts of MSNA provides novel, mechanistic insight into sympathetic neural control of the circulation. Although some of these laboratories have developed in-house software programs to analyze these sympathetic transduction responses, they are not openly available and most require higher level programming skills and/or costly platforms. In the present paper, we present an open-source, Microsoft Excel-based analysis program designed to examine the pressor and/or vascular responses to spontaneous resting bursts of MSNA, including across longer, continuous MSNA burst sequences, as well as following heartbeats not associated with MSNA bursts. An Excel template with embedded formulas is provided. Detailed written and video-recorded instructions are provided to help facilitate the user and promote its implementation among the research community. Open science activities such as the dissemination of analytical programs and instructions may assist other laboratories in their pursuit to answer novel and impactful research questions regarding sympathetic neural control strategies in human health and disease.NEW & NOTEWORTHY The pressor responses to spontaneous bursts of muscle sympathetic nerve activity provide important information regarding sympathetic regulation of the circulation. Many laboratories worldwide quantify sympathetic neurohemodynamic transduction using in-house, customized software requiring high-level programming skills and/or costly computer programs. To overcome these barriers, this study presents a simple, open-source, Microsoft Excel-based analysis program along with video instructions to assist researchers without the necessary resources to quantify sympathetic neurohemodynamic transduction.

Aerobic fitness and sympathetic responses to spontaneous muscle sympathetic nerve activity in young males.

PURPOSE: Lower aerobic fitness increases the risk of developing hypertension. Muscle sympathetic nerve activity (MSNA) is important for the beat-by-beat regulation of blood pressure. Whether the cardiovascular consequences of lower aerobic fitness are due to augmented transduction of MSNA into vascular responses is unclear. We tested the hypothesis that aerobic fitness is inversely related to peak increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) in response to spontaneous MSNA bursts in young males. METHODS: Relative peak oxygen consumption (VO2peak, indirect calorimetry) was assessed in 18 young males (23 ± 3 years; 41 ± 8 ml/kg/min). MSNA (microneurography), cardiac intervals (electrocardiogram) and arterial pressure (finger photoplethysmography) were recorded continuously during supine rest. Stroke volume and cardiac output (CO) were estimated via the ModelFlow method. TPR was calculated as MAP/CO. Changes in TPR and MAP were tracked for 12 cardiac cycles following heartbeats associated with or without spontaneous bursts of MSNA. RESULTS: Overall, aerobic fitness was inversely correlated to the peak ΔTPR (0.8 ± 0.7 mmHg/l/min; R = - 0.61, P = 0.007) and ΔMAP (2.3 ± 0.8 mmHg; R = - 0.69, P < 0.001), but not with the peak ΔCO (0.2 ± 0.1 l/min; P = 0.50), MSNA burst frequency (14 ± 5 bursts/min; P = 0.43) or MSNA relative burst amplitude (65 ± 12%; P = 0.13). Heartbeats without an associated burst of MSNA did not increase TPR, MAP or CO. CONCLUSION: Although unrelated to traditional MSNA characteristics, aerobic fitness was inversely associated with spontaneous sympathetic neurovascular transduction in young males. This may be a potential mechanism by which aerobic fitness modulates the regulation of arterial blood pressure through the sympathetic nervous system.

Does aerobic fitness impact prolonged sitting-induced popliteal artery endothelial dysfunction?

PURPOSE: Acute prolonged bouts of sitting reduce popliteal artery blood flow and flow-mediated dilation (FMD). Individuals with higher aerobic fitness have enhanced popliteal FMD. Conflicting evidence regarding whether more aerobically fit individuals are protected from the negative impacts of sitting on popliteal endothelial function in male-dominated studies have been reported. We further explored the relationship between aerobic fitness and sitting-induced impairments in popliteal blood flow and FMD in a more sex-balanced cohort. METHODS: Relative peak oxygen consumption (V̇O2peak) was assessed using a cycling-based incremental test in 21 healthy adults (eight males; 23 ± 2 years; 23.9 ± 2.9 kg/m2). Popliteal blood flow and relative FMD (%) were measured via duplex ultrasonography before and after 3 h of uninterrupted sitting. Pearson correlations were performed separately between V̇O2peak versus pre-sitting and sitting-induced reductions in popliteal outcomes. RESULTS: Aerobic fitness (41.0 ± 9.7 ml/kg/min) was positively correlated with pre-sitting popliteal blood flow (65 ± 23 mL/min; R = 0.59, P = 0.005) and relative FMD (4.2 ± 1.5%; R = 0.49, P = 0.03). As expected, sitting reduced resting blood flow (19 ± 11 mL/min) and FMD (1.9 ± 0.7%) (both, P < 0.001). V̇O2peak was inversely related to sitting-induced declines in blood flow (Δ-46 ± 23 mL/min; R = - 0.71, P < 0.001) and FMD (Δ-2.4 ± 1.5%; R = - 0.51, P = 0.02). CONCLUSIONS: Although higher aerobic fitness was associated with more favorable popliteal endothelial-dependent vasodilator responses, it also corresponded with larger sitting-induced impairments in FMD. This suggests that being more aerobically fit does not protect against sitting-induced vascular endothelial dysfunction. As such, all young adults should minimize habitual prolonged sedentary bouts, regardless of their aerobic fitness level.

Flattened cola improves high-intensity interval performance in competitive cyclists.

PURPOSE: Some cyclists consume flattened cola during competitive events, but limited research has investigated if cola beverages elicit ergogenic effects, particularly on high-intensity exercise performance. Whether the potentially beneficial effects of cola are due to the caffeine and/or the carbohydrate content is also unclear. This study assessed the ergogenic effects of different cola beverages on performance during a constant power bout (CPB) and subsequent high-intensity interval efforts in competitive cyclists. METHODS: In a randomized, double-blind, cross-over design, competitive cyclists (n = 13; [Formula: see text]O2max 65.7 ± 5.9 ml kg-1 min-1) completed a 45-min CPB at 69% of maximum workload (Wmax), followed by four maximal 1-min high-intensity intervals (HII) against a resistance of 0.5 N kg-1. Participants consumed 16 ml kg-1 total (intermittantly at four time points) of flattened decaffinated diet cola (PLA), caffeinated diet cola (CAF) or cola containing caffeine and carbohydrates (CAF + CHO). RESULTS: During the CPB, ratings of perceived exertion were lower in the CAF + CHO and CAF conditions compared to PLA (both, P < 0.04). Compared to PLA, CAF + CHO and CAF similarly increased (all, P < 0.049) mean power (CAF + CHO: 448 ± 51 W; CAF: 448 ± 50 W; PLA: 434 ± 57 W), minimum power (CAF + CHO: 353 ± 45 W; CAF: 352 ± 51 W; PLA: 324 ± 49 W) and total work (CAF + CHO: 26.9 ± 3.1 kJ; CAF: 26.9 ± 3.0 kJ; PLA: 26.0 ± 3.4 kJ), but not peak power (CAF + CHO: 692 ± 117 W; CAF: 674 ± 114 W; PLA: 670 ± 113 W; all, P > 0.57) during the HII. CONCLUSION: Cola containing caffeine with or without carbohydrates favorably influenced perceived effort during the CPB and enhanced mean and minimum power during repeated maximal intervals. We provide evidence supporting the consumption of commercially available cola for high-intensity cycling in competitive cyclists.

Improving the criterion validity of the activPAL in determining physical activity intensity during laboratory and free-living conditions.

The activPAL is a valid measure of step counts and posture, but its ability to determine physical activity intensity is unclear. This study tested the criterion validity of the activPAL using its built-in linear cadence-metabolic equivalents (METs) equation (activPAL-linear) versus an individualized height-adjusted curvilinear cadence-METs equation (activPAL-curvilinear) to estimate intensity-related physical activity. Forty adults (25±6 years, 23.3±4.1 kg/m2) wore an activPAL during a 7-stage progressive treadmill walking protocol (criterion: indirect calorimetry). A sub-sample (n=32) wore the device during free-living conditions for 7-days (criterion: PiezoRxD monitor). In the laboratory, the activPAL-linear overestimated METs during slow walking (1.5-3.0 miles•hour-1) but underestimated METs during fast walking (3.5-4.5 miles•hour-1) (all, p<0.001). In the free-living condition, the activPAL-linear overestimated time in light-intensity activity and underestimated moderate-intensity activity (both, p<0.001), but did not register any vigorous-intensity activity. In contrast, the activPAL-curvilinear estimated values statistically equivalent to indirect calorimetry for treadmill stages 1-6 (1.5-4.0 miles•hour-1) and to the PiezoRxD determined light- and moderate-intensity activity during free-living. We present a simple, data processing technique that uses an alternative curvilinear cadence-MET equation that improves the ability of the activPAL to measure intensity-related physical activity in both laboratory and free-living settings.