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Abstract Background High sedentary times (ST) is highly prevalent in patients with coronary artery disease (CAD), highlighting the need for behavioural change interventions that effectively reduce ST. We examined the immediate and medium-term effect of the SIT LESS intervention on changes in ST among CAD patients enrolled in cardiac rehabilitation (CR). Methods CAD patients participating in CR at 2 regional hospitals were included in this randomized controlled trial (1:1, stratified for gender and hospital). The control group received CR, whereas SIT LESS participants additionally received a 12-week hybrid behaviour change intervention. The primary outcome was the change in accelerometer-derived ST from pre-CR to post-CR and 3 months post-CR. Secondary outcomes included changes in ST and physical activity characteristics, subjective outcomes, and cardiovascular risk factors. A baseline constrained linear mixed-model was used. Results Participants (23% female; SIT LESS: n = 108, control: n = 104) were 63 ± 10 years. Greater ST reductions were found for SIT LESS compared to control post-CR (-1.7 (95% confidence interval (CI): -2.0; -1.4) versus − 1.1 (95% CI: -1.4; -0.8) h/day, pinteraction=0.009), but not at 3 months post-CR (pinteraction=0.61). Besides, larger light-intensity physical activity (LIPA) increases were found for SIT LESS compared to control post-CR (+ 1.4 (95% CI: +1.2; +1.6) versus + 1.0 (95% CI: +0.8; +1.3) h/day, pinteraction=0.020). Changes in other secondary outcomes did not differ among groups. Conclusion SIT LESS transiently reduced ST and increased LIPA, but group differences were no longer significant 3 months post-CR. These findings highlight the challenge to induce sustainable behaviour changes in CAD patients without any continued support. Trial registration Netherlands Trial Register: NL9263. Registration Date: 24 February 2021.

Abstract Background Previous cross-sectional and longitudinal observational studies revealed positive relationships between contextual built environment components and walking behavior. Due to severe restrictions during COVID-19 pandemic lockdowns, physical activity was primarily performed within the immediate living area. Using this unique opportunity, we evaluated whether built environment components were associated with the magnitude of change in walking activity in adults during COVID-19 restrictions. Methods Data on self-reported demographic characteristics and walking behaviour were extracted from the prospective longitudinal Lifelines Cohort Study in the Netherlands of participants ≥ 18 years. For our analyses, we made use of the data acquired between 2014–2017 (n = 100,285). A fifth of the participants completed the questionnaires during COVID-19 restrictive policies in July 2021 (n = 20,806). Seven spatial components were calculated for a 500m and 1650m Euclidean buffer per postal code area in GIS: population density, retail and service destination density, land use mix, street connectivity, green space density, sidewalk density, and public transport stops. Additionally, the walkability index (WI) of these seven components was calculated. Using multivariable linear regression analyses, we analyzed the association between the WI (and separate components) and the change in leisure walking minutes/week. Included demographic variables were age, gender, BMI, education, net income, occupation status, household composition and the season in which the questionnaire was filled in. Results The average leisure walking time strongly increased by 127 min/week upon COVID-19 restrictions. All seven spatial components of the WI were significantly associated with an increase in leisure walking time; a 10% higher score in the individual spatial component was associated with 5 to 8 more minutes of leisure walking/week. Green space density at the 500m Euclidean buffer and side-walk density at the 1650m Euclidean buffer were associated with the highest increase in leisure walking time/week. Subgroup analysis revealed that the built environment showed its strongest impact on leisure walking time in participants not engaging in leisure walking before the COVID-19 pandemic, compared to participants who already engaged in leisure walking before the COVID-19 pandemic. Conclusions These results provide strong evidence that the built environment, corrected for individual-level characteristics, directly links to changes observed in leisure walking time during COVID-19 restrictions. Since this relation was strongest in those who did not engage in leisure walking before the COVID-19 pandemic, our results encourage new perspectives in health promotion and urban planning.

BackgroundDespite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR.MethodsThe retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care.ResultsIn total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40–0.68).ConclusionThe present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

Abstract Background In postmenopausal women, reduced ovarian function precedes endothelial dysfunction and attenuated endothelial resistance to ischemia‐reperfusion (IR) injury. We hypothesized that IR injury would lower endothelial function, with premenopausal women demonstrating the greatest protection from injury, followed by early, then late postmenopausal women. Methods Flow‐mediated dilation (FMD) was assessed at baseline and following IR injury in premenopausal (n = 11), early (n = 11; 4 ± 1.6 years since menopause), and late (n = 11; 15 ± 5.5 years since menopause) postmenopausal women. Results There were significant group differences in baseline FMD (p = 0.007); post hoc analysis revealed a similar resting FMD between premenopausal (7.8% ± 2.1%) and early postmenopausal (7.1% ± 2.7%), but significantly lower FMD in late postmenopausal women (4.5% ± 2.3%). Results showed an overall decline in FMD after IR injury (p

Abstract Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).

Background Little is known about changes in physical activity (PA) and sedentary behavior (SB) patterns in the acute phase of a myocardial infarction (MI). We objectively assessed PA and SB during hospitalization and the first week after discharge. Methods and Results Consecutively admitted patients hospitalized with an MI were approached to participate in this prospective cohort study. SB, light‐intensity PA, and moderate‐vigorous intensity PA were objectively assessed for 24 h/d during hospitalization and up to 7 days after discharge in 165 patients. Changes in PA and SB from the hospital to home phase were evaluated using mixed‐model analyses, and outcomes were stratified for predefined subgroups based on patient characteristics. Patients (78% men) were aged 65±10 years and diagnosed with ST‐segment–elevation MI (50%) or non–ST‐segment–elevation MI (50%). Sedentary time was high during hospitalization (12.6 [95% CI, 11.8–13.7] h/d) but substantially decreased following transition to the home environment (−1.8 [95% CI, −2.4 to −1.3] h/d). Furthermore, the number of prolonged sedentary bouts (≥60 minutes) decreased between hospital and home (−1.6 [95% CI, −2.0 to −1.2] bouts/day). Light‐intensity PA (1.1 [95% CI, 0.8–1.6] h/d) and moderate‐vigorous intensity PA (0.2 [95% CI, 0.1–0.3] h/d) were low during hospitalization but significantly increased following transition to the home environment (light‐intensity PA: 1.8 [95% CI, 1.4–2.3] h/d; moderate‐vigorous intensity PA: 0.4 [95% CI, 0.3–0.5] h/d; both P

Background Regular exercise training is an important factor in prevention of myocardial infarction (MI). However, little is known whether exercise engagement prior to MI is related to the magnitude of post-MI cardiac biomarker concentrations and clinical outcomes.Objectives We tested the hypothesis that exercise engagement in the week prior MI is related to lower cardiac biomarker concentrations following ST-elevated MI (STEMI).Methods We recruited hospitalised STEMI patients and assessed the amount of exercise engagement in the 7 days preceding MI onset using a validated questionnaire. Patients were classified as ‘exercise’ if they performed any vigorous exercise in the week prior MI, or as ‘control’ if they did not. Post-MI peak concentrations of high-sensitive cardiac troponin T (peak-hs-cTnT) and creatine kinase (peak-CK) were examined. We also explored whether exercise engagement prior MI is related to the clinical course (duration of hospitalisation and incidence of in-hospital, 30-day and 6-month major adverse cardiac events (reinfarction, target vessel revascularisation, cardiogenic shock or death)).Results In total, 98 STEMI patients were included, of which 16% (n=16) was classified as ‘exercise’, and 84% (n=82) as ‘control’. Post-MI peak-hs-cTnT and peak-CK concentrations were lower in the exercise group (941 (645–2925) ng/mL; 477 (346–1402) U/L, respectively) compared with controls (3136 (1553–4969) ng/mL, p=0.010; 1055 (596–2019) U/L, p=0.016, respectively). During follow-up, no significant differences were found between both groups.Conclusion Engagement in exercise is associated with lower cardiac biomarker peak concentrations following STEMI. These data could provide further support for the cardiovascular health benefits of exercise training.

Abstract Background Identification of characteristics of individuals that are related to decreases in physical activity (PA) levels during lockdown is needed to develop targeted-interventions. This study aims to evaluate changes in domain-specific (i.e. leisure time, transportation, occupational, and household) and total PA due to the Dutch COVID-19 lockdown, which started on March 15 2020. Furthermore, we aim to identify demographic, health-related, and psychological correlates of these changes. Methods Individuals who participated in the Nijmegen Exercise Study during 2017-2019 were invited to this study, which was conducted between April 16 and May 12 2020. Participant characteristics (i.e. age, sex, body mass index (BMI), marital status, education, household composition, and occupation status), living environment (i.e. housing type and degree of urbanization), psychological characteristics (i.e. resilience, outcome expectations, vitality, and mental health), and medical history were collected via an online questionnaire. Short Questionnaire to Assess Health-enhancing physical activity was used to assess PA behavior before and during lockdown. Wilcoxon signed-rank test was used to compare PA levels, in metabolic equivalent of task (MET)-minutes per week (min/wk), before and during lockdown. Multivariable linear regression analyses were performed to examine correlates of PA changes. Results 4033 participants (57% male; 59 ± 13 years) were included. PA decreased significantly during lockdown with mean ± SD changes of 393 ± 2735 MET-min/wk for total, 133 ± 785 MET-min/wk for transportation, 137 ± 1469 MET-min/wk for occupation, and 136 ± 1942 MET-min/wk for leisure time PA. Household PA did not change significantly. Unemployment, COVID-19-related occupational changes, higher BMI, and living in an apartment or semi-detached/terraced house were significantly related to larger decreases in total and domain-specific PA. Higher vitality was related to smaller decreases in total and domain-specific PA. Higher age was significantly associated with a larger decrease in leisure time PA. Lower education was associated with smaller decreases in transportation and occupational PA compared to higher education. Conclusion PA levels significantly reduced during lockdown compared to before lockdown. Declines were observed during transportation and occupation, but were not compensated by an increase in leisure time PA. We identified subgroups that were more susceptible to reductions in domain-specific or total PA levels and should therefore be encouraged to increase their PA levels during lockdown.

Abstract Introduction Knowledge, once acquired, degrades over time. Exams that contain questions related to previously acquired knowledge (‘retrieval practice questions’) may promote retrieval practice and spaced learning, and subsequently prevent knowledge loss. To investigate this hypothesis, we compare the score of retrieval practice questions to regular questions in exams of a two-year (bio)medical study program. Methods The two-year “Mechanisms of Health and Disease”-program for biomedical sciences and medical students in Nijmegen (the Netherlands) contains 14 spaced exams of 80 questions each. The percentages of correct-, false-, and non-answers were compared between regular questions and retrieval practice questions. Using Pearson correlations between question scores and exam scores (RiT-values), the impact of retrieval practice questions on the internal consistency of exams was determined. Mixed model analyses determined changes in outcomes across time. Results Analysis of 2006 regular questions and 1728 retrieval practice questions revealed a significantly higher percentage of correct and false answers, and a significantly lower percentage of non-answers, in retrieval practice questions versus regular questions (all P

BackgroundEthnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness.MethodsData were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness.ResultsWe included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans.ConclusionEthnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors.

Background: Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic preconditioning on inflammatory biomarkers in patients with cerebral small vessel disease (cSVD).Methods: In this crossover study, 14 patients with cSVD were included. All participants performed 4-day of handgrip exercise (4x5-minutes at 30% of maximal handgrip strength) and remote ischemic preconditioning (rIPC; 4x5-minutes cuff occlusion around the upper arm) twice daily. Patients were randomized to start with either handgrip exercise or rIPC and the two interventions were separated by > 9 days. Venous blood was drawn before and after one intervention, and after 4-day of repeated exposure. We performed a targeted proteomics on inflammation markers in all blood samples.Results: Targeted proteomics revealed significant changes in 9 out of 92 inflammatory proteins, with four proteins demonstrating comparable time-dependent effects between handgrip and rIPC. After adjustment for multiple testing we found significant decreases in FMS-related tyrosine kinase-3 ligand (Flt3L; 16.2% reduction; adjusted p-value: 0.029) and fibroblast growth factor-21 (FGF-21; 32.8% reduction adjusted p-value: 0.029) after single exposure. This effect did not differ between handgrip and rIPC. The decline in Flt3L after repeated handgrip and rIPC remained significant (adjusted p-value = 0.029), with no difference between rIPC and handgrip (adjusted p-value = 0.98).Conclusion: Single handgrip exercise and rIPC immediately attenuated plasma Flt3L and FGF-21, with the reduction of Flt3L remaining present after 4-day of repeated intervention, in people with cSVD. This suggests that single and repeated handgrip exercise and rIPC decrease comparable inflammatory biomarkers, which suggests activation of shared (anti-)inflammatory pathways following both stimuli. Additional studies will be needed to exclude the possibility that this activation is merely a time effect.

ObjectiveDual pathway inhibition (DPI) by combining acetylsalicylic acid (ASA) with low-dose rivaroxaban has been shown to reduce cardiovascular events in patients with peripheral arterial disease (PAD) when compared to ASA monotherapy. A potential explanation is that inhibition of factor Xa improves endothelial function through crosstalk between coagulation and inflammatory pathways, subsequently attenuating the occurrence of cardiovascular events. We hypothesize that the addition of rivaroxaban to ASA in PAD patients leads to improved endothelial function.DesignAn investigator-initiated, multicentre trial investigating the effect of DPI on endothelial function.MethodsPatients, diagnosed with PAD, were enrolled in two cohorts: cohort A (Rutherford I-III) and cohort B (Rutherford IV-VI). Participants received ASA monotherapy for a 4-weeks run-in period, followed by 12 weeks of DPI. Macro- and microvascular endothelial dysfunction were studied by measuring carotid artery reactivity upon sympathetic stimulus and by measuring plasma endothelin-1 concentrations, respectively. All measurements were performed during the use of ASA (baseline) and after 12 weeks of DPI.Results159 PAD patients (111 cohort A, 48 cohort B) were enrolled. Twenty patients discontinued study drugs early. Carotid artery constriction upon sympathetic stimulation at baseline (ASA) and after 12 weeks of DPI was similar in the total group, 22.0 vs. 22.7% (p = 1.000), and in the subgroups (Cohort A 22.6 vs. 23.7%, p = 1.000; cohort B 20.5 vs. 20.5%, p = 1.000), respectively. The mean concentration of plasma endothelin-1 at baseline and after 12 weeks of DPI did not differ, 1.70 ± 0.5 vs. 1.66 ± 0.64 pmol/L (p = 0.440) in the total group, 1.69 ± 0.59 vs. 1.62 ± 0.55 pmol/L in cohort A (p = 0.202), and 1.73 ± 0.53 vs. 1.77 ± 0.82 pmol/L in cohort B (p = 0.682), respectively.ConclusionMacro- and microvascular endothelial dysfunction, as reflected by carotid artery reactivity and plasma endothelin-1 concentrations, are not influenced in PAD patients by addition of low-dose rivaroxaban to ASA monotherapy for 12 weeks.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04218656.

Abstract It is well‐known that aerobic exercise training beneficially affects endothelial function as measured by brachial artery flow‐mediated vasodilation (FMD). This trial with older sedentary overweight and obese men, therefore, examined the effects of aerobic training on other non‐invasive markers of the vasculature, which have been studied in less detail. Seventeen men (67 ± 2 years, BMI: 30.3 ± 2.8 kg/m2) participated in this controlled cross‐over study. Study participants followed in random order a fully supervised, progressive, aerobic exercise training (three 50‐min sessions each week at 70% maximal power) and a no‐exercise control period for 8 weeks, separated by a 12‐week wash‐out period. At the end of each period, endothelial function was assessed by the carotid artery reactivity (CAR) response to a cold pressor test and FMD, and local carotid and regional aortic stiffness by the carotid‐to‐femoral pulse wave velocity (PWVc–f). The retinal microvasculature, the serum lipid profile, 24‐h ambulatory blood pressure, and 96‐h continuous glucose concentrations were also determined. Aerobic training increased CAR from 1.78% to 4.01% (Δ2.23 percentage point [pp]; 95% CI: 0.58, 3.89 pp; p = 0.012) and FMD from 3.88% to 6.87% (Δ2.99 pp; 95% CI: 0.58, 5.41 pp; p = 0.019). The stiffness index β0 increased by 1.1 (95% CI: 0.3, 1.9; p = 0.012), while PWVc–f did not change. Retinal arteriolar width increased by 4 μm (95% CI: 0, 7 μm; p = 0.041). Office blood pressure decreased, but ambulatory blood pressure, and serum lipid and continuous glucose concentrations did not change. Aerobic exercise training improved endothelial function and retinal arteriolar width in older sedentary overweight and obese men, which may reduce cardiovascular risk.

Background: Regular exercise is an effective non-pharmacological therapy for treatment and prevention of cardiovascular disease (CVD). The therapeutic benefits of exercise are mediated partly through improved vascular and increase in metabolic health. Release of exercise-responsive myokines, including irisin, is associated with beneficial effects of exercise in CVD patients.Observations: The present review provides an overview of the role of exercise in cardiac rehabilitation of patients with myocardial infarction (MI). Further, the role of irisin as a motion-responsive molecule in improving vascular and metabolic health is explored. Possible mechanism of cardioprotective effect of irisin-mediated exercise on myocardial infarction are also summarized in this review.Conclusion and significance of the review: Irisin is associated with reduced inflammation, antioxidant properties, and anti-apoptotic effect, implying that it is a potential key mediator of the beneficial effects of exercise on vascular and metabolic health. The findings show that irisin is a promising therapeutic target for treatment of patients with cardiovascular disease, particularly post-MI. Further research should be conducted to elucidate the potential mechanisms of cardioprotective effects of irisin and explored whether irisin induced by exercise exerts rehabilitation effects post-MI.

In healthy persons, there is an excellent relation between the timing of the (two) surface electromyography (sEMG) thresholds and the (two) ventilatory thresholds during exercise. The primary aim of this study was to determine the relative timing of both sEMG and ventilatory thresholds in patients with neuromuscular disorders compared with healthy subjects during a maximal ergospirometry cycling test. We hypothesized that in patients with neuromuscular disorders, the sEMG thresholds would occur relatively earlier in time than the ventilatory thresholds, compared to healthy subjects, because performance fatigability occurs more rapidly. In total, 24 healthy controls and 32 patients with a neuromuscular disorder performed a cardiopulmonary exercise test on a bicycle using a 10-min ramp protocol, during which we collected ergospirometry data: power at both ventilatory and sEMG thresholds, and sEMG data of lower leg muscles. In line with our hypothesis, normalized values for all thresholds were lower for patients than healthy subjects. These differences were significant for the first ventilatory (p = 0.008) and sEMG threshold (p < 0.001) but not for the second sEMG (p = 0.053) and ventilatory threshold (p = 0.238). Most parameters for test–retest reliability of all thresholds did not show any fixed bias, except for the second ventilatory threshold. The feasibility of the sEMG thresholds was lower than the ventilatory thresholds, particularly of the first sEMG threshold. As expected, the sEMG thresholds, particularly the first threshold, occurred relatively earlier in time than the ventilatory thresholds in patients compared with healthy subjects. A possible explanation could be (a combination of) a difference in fiber type composition, disuse, and limited muscle-specific force in patients with neuromuscular disorders. sEMG measurements during submaximal dynamic exercises are needed to generalize the measurements to daily life activities for future use in prescribing and evaluating rehabilitation interventions.

Abstract Background Subjective measures of sedentary behaviour (SB) (i.e. questionnaires and diaries/logs) are widely implemented, and can be useful for capturing type and context of SBs. However, little is known about comparative validity and reliability. The aim of this systematic review and meta-analysis was to: 1) identify subjective methods to assess overall, domain- and behaviour-specific SB, and 2) examine the validity and reliability of these methods. Methods The databases MEDLINE, EMBASE and SPORTDiscus were searched up to March 2020. Inclusion criteria were: 1) assessment of SB, 2) evaluation of subjective measurement tools, 3) being performed in healthy adults, 4) manuscript written in English, and 5) paper was peer-reviewed. Data of validity and/or reliability measurements was extracted from included studies and a meta-analysis using random effects was performed to assess the pooled correlation coefficients of the validity. Results The systematic search resulted in 2423 hits. After excluding duplicates and screening on title and abstract, 82 studies were included with 75 self-reported measurement tools. There was wide variability in the measurement properties and quality of the studies. The criterion validity varied between poor-to-excellent (correlation coefficient [R] range − 0.01- 0.90) with logs/diaries (R = 0.63 [95%CI 0.48–0.78]) showing higher criterion validity compared to questionnaires (R = 0.35 [95%CI 0.32–0.39]). Furthermore, correlation coefficients of single- and multiple-item questionnaires were comparable (1-item R = 0.34; 2-to-9-items R = 0.35; ≥10-items R = 0.37). The reliability of SB measures was moderate-to-good, with the quality of these studies being mostly fair-to-good. Conclusion Logs and diaries are recommended to validly and reliably assess self-reported SB. However, due to time and resources constraints, 1-item questionnaires may be preferred to subjectively assess SB in large-scale observations when showing similar validity and reliability compared to longer questionnaires. Registration number CRD42018105994.

Abstract Background Sedentary behaviour might be a potential risk factor for cognitive decline. However, the short-term effects of sedentary behaviour on (cerebro) vascular and cognitive performance in older people are unknown. Methods We used a cross-over design with 22 older adults (78 years, 9 females) to assess the short-term hemodynamic and cognitive effects of three hours uninterrupted sitting and explored if these effects can be counteracted with regular (every 30 min) two-minute walking breaks. In addition, we investigated if low versus high mental activity during the three hours of sitting modified these effects. Before and after each condition, alertness, executive functioning, and working memory were assessed with the Test of Attentional Performance battery. Additionally, cerebral blood flow velocity (Transcranial Doppler) and blood pressure (Finapres) were measured in rest, and during sit-to-stand and CO2 challenges to assess baroreflex sensitivity, cerebral autoregulation, and cerebral vasomotor reactivity. Results No short-term differences were observed in cognitive performance, cerebral blood flow velocity, baroreflex sensitivity, cerebral autoregulation, or cerebral vasomotor reactivity across time, or between conditions. Blood pressure and cerebrovascular resistance increased over time (8.6 mmHg (5.0;12.1), p

Abstract Background Sedentary behavior (SB) is associated with increased risks of detrimental health outcomes. Few studies have explored correlates of SB in physically active individuals. Furthermore, SB correlates may depend on settings of SB, such as occupation, transportation and leisure time sitting. This study aims to identify subject-, lifestyle- and health-related correlates for total SB and different SB domains: transportation, occupation, and leisure time. Methods Dutch participants were recruited between June, 2015 and December, 2016. Participant characteristics (i.e. age, sex, weight, height, marital status, education level, employment), lifestyle (sleep, smoking, alcohol consumption, physical activity) and medical history were collected via an online questionnaire. SB was assessed using the Sedentary Behavior Questionnaire and estimated for 9 different activities during weekdays and weekend days. Logistic regression was used to calculate odds ratios and 95% confidence intervals for the association between correlates and SB. Total SB was dichotomized at > 8 h/day and > 10 h/day, and being sedentary during transportation, occupation and leisure time at the 75th percentile (60 min/day, 275 min/day and 410 min/day, respectively). Results In total, 8471 participants (median age 55, 55% men) were included of whom 86% met the physical activity guidelines. Median SB was 9.1 h/day (Q25 6.3-Q75 12.0) during weekdays and 7.4 h/day (Q25 5.5-Q75 9.5) during weekend days. SB was most prevalent during leisure time (5.3 h/day; Q25 3.9-Q75 6.8), followed by occupation (2 h/day; Q25 0.1-Q75 4.6) and transportation (0.5 h/day; Q25 0.2-Q75 1.0). Younger age, male sex, being unmarried, higher education, employment and higher BMI were significantly related to higher levels of total SB. Younger age, male sex, employment, and higher BMI increased the odds for high SB volumes during occupation and transportation. Higher education, being unmarried and smoking status were positively associated with high volumes of occupational SB only, whereas older age, being unmarried, unemployment, higher BMI and poor health were positively linked to leisure time SB. Conclusions SB is highly prevalent in physically active individuals, with SB during leisure time as the most important contributor. Correlates for high volumes of SB vary substantially across SB domains, emphasizing the difficulty to target this unhealthy lifestyle.

BackgroundModerate to vigorous physical activity (MVPA) is strongly associated with risk reductions of noncommunicable diseases and mortality. Cardiovascular health status may influence the benefits of MVPA. We compare the association between MVPA and incident major adverse cardiovascular events (MACE) and mortality between healthy individuals, individuals with elevated levels of cardiovascular risk factors (CVRF), and cardiovascular disease (CVD).Methods and findingsA cohort study was performed in the 3 northern provinces of the Netherlands, in which data were collected between 2006 and 2018, with a median follow-up of 6.8 years (Q25 5.7; Q75 7.9). A total of 142,493 participants of the Lifelines Cohort Study were stratified at baseline as (1) healthy; (2) CVRF; or (3) CVD. Individuals were categorized into "inactive" and 4 quartiles of least (Q1) to most (Q4) active based on self-reported MVPA volumes. Primary outcome was a composite of incident MACE and all-cause mortality during follow-up. Cox regression was used to estimate hazard ratios (HRs), 95% confidence intervals (CIs) and P values. The main analyses were stratified on baseline health status and adjusted for age, sex, income, education, alcohol consumption, smoking, protein, fat and carbohydrate intake, kidney function, arrhythmias, hypothyroid, lung disease, osteoarthritis, and rheumatoid arthritis. The event rates were 2.2% in healthy individuals (n = 2,485 of n = 112,018), 7.9% in those with CVRF (n = 2,214 of n = 27,982) and 40.9% in those with CVD (n = 1,019 of n = 2,493). No linear association between MVPA and all-cause mortality or MACE was found for healthy individuals (P = 0.36) and individuals with CVRF (P = 0.86), but a linear association was demonstrated for individuals with CVD (P = 0.04). Adjusted HRs in healthy individuals were 0.81 (95% CI 0.64 to 1.02, P = 0.07), 0.71 (95% CI 0.56 to 0.89, P = 0.004), 0.72 (95% CI 0.57 to 0.91, P = 0.006), and 0.76 (95% CI 0.60 to 0.96, P = 0.02) for MVPA Q1 to Q4, respectively, compared to inactive individuals. In individuals with CVRF, HRs were 0.69 (95% CI 0.57 to 0.82, P < 0.001), 0.66 (95% CI 0.55 to 0.80, P < 0.001), 0.64 (95% CI 0.53 to 0.77, P < 0.001), and 0.69 (95% CI 0.57 to 0.84, P < 0.001) for MVPA Q1 to Q4, respectively, compared to inactive individuals. Finally, HRs for MVPA Q1 to Q4 compared to inactive individuals were 0.80 (95% CI 0.62 to 1.03, P = 0.09), 0.82 (95% CI 0.63 to 1.06, P = 0.13), 0.74 (95% CI 0.57 to 0.95, P = 0.02), and 0.70 (95% CI 0.53 to 0.93, P = 0.01) in CVD patients. Leisure MVPA was associated with the most health benefits, nonleisure MVPA with little health benefits, and occupational MVPA with no health benefits. Study limitations include its observational nature, self-report data about MVPA, and potentially residual confounding despite extensive adjustment for lifestyle risk factors and health-related factors.ConclusionsMVPA is beneficial for reducing adverse outcomes, but the shape of the association depends on cardiovascular health status. A curvilinear association was found in healthy and CVRF individuals with a steep risk reduction at low to moderate MVPA volumes and benefits plateauing at high(er) MVPA volumes. CVD patients demonstrated a linear association, suggesting a constant reduction of risk with higher volumes of MVPA. Therefore, individuals with CVDs should be encouraged that "more is better" regarding MVPA. These findings may help to optimize exercise prescription to gain maximal benefits of a physically active lifestyle.

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism.Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes.Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR.” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet.Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419.

Background There is limited evidence of long‐term impact of exercise‐based cardiac rehabilitation (CR) on clinical end points for patients with atrial fibrillation (AF). We therefore compared 18‐month all‐cause mortality, hospitalization, stroke, and heart failure in patients with AF and an electronic medical record of exercise‐based CR to matched controls. Methods and Results This retrospective cohort study included patient data obtained on February 3, 2021 from a global federated health research network. Patients with AF undergoing exercise‐based CR were propensity‐score matched to patients with AF without exercise‐based CR by age, sex, race, comorbidities, cardiovascular procedures, and cardiovascular medication. We ascertained 18‐month incidence of all‐cause mortality, hospitalization, stroke, and heart failure. Of 1 366 422 patients with AF, 11 947 patients had an electronic medical record of exercise‐based CR within 6‐months of incident AF who were propensity‐score matched with 11 947 patients with AF without CR. Exercise‐based CR was associated with 68% lower odds of all‐cause mortality (odds ratio, 0.32; 95% CI, 0.29–0.35), 44% lower odds of rehospitalization (0.56; 95% CI, 0.53–0.59), and 16% lower odds of incident stroke (0.84; 95% CI, 0.72–0.99) compared with propensity‐score matched controls. No significant associations were shown for incident heart failure (0.93; 95% CI, 0.84–1.04). The beneficial association of exercise‐based CR on all‐cause mortality was independent of sex, older age, comorbidities, and AF subtype. Conclusions Exercise‐based CR among patients with incident AF was associated with lower odds of all‐cause mortality, rehospitalization, and incident stroke at 18‐month follow‐up, supporting the provision of exercise‐based CR for patients with AF.

Abstract Purpose The aim of this study was to examine if catechin‐rich green tea abrogates the negative effects of 7‐days of physical inactivity and excessive calorie‐intake on insulin homeostasis and peripheral vascular function. Methods Using a randomized, double‐blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7‐days unhealthy lifestyle (UL), including physical inactivity (−50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL‐tea; 3 doses/day) or placebo (UL‐placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3‐h after a 1,202 kcal meal) and upper and lower limb vascular function (flow‐mediated dilation (FMD%)) and carotid artery reactivity (CAR%). Results UL‐placebo increased postprandial glucose and insulin, while UL‐tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p 0.05) for brachial FMD%. Conclusion Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin‐rich green tea.

Whilst both cardiac output (CO) and total peripheral resistance (TPR) determine mean arterial blood pressure (MAP), their relative importance in the pressor response to isometric exercise remains unclear. This study aimed to elucidate the relative importance of these two different factors by examining pressor responses during cardiopulmonary unloading leading to step-wise reductions in CO. Hemodynamics were investigated in 11 healthy individuals before, during and after two-minute isometric exercise during lower body negative pressure (LBNP; -20mmHg and -40mmHg). The blood pressure response to isometric exercise was similar during normal and reduced preload, despite a step-wise reduction in CO during LBNP (-20mmHg and -40mmHg). During -20mmHg LBNP, the decreased stroke volume, and consequently CO, was counteracted by an increased TPR, while heart rate (HR) was unaffected. HR was increased during -40 mmHg LBNP, although insufficient to maintain CO; the drop in CO was perfectly compensated by an increased TPR to maintain MAP. Likewise, transient application of LBNP (-20mmHg and -40mmHg) resulted in a short transient drop in MAP, caused by a decrease in CO, which was compensated by an increase in TPR. This study suggests that, in case of reductions of CO, changes in TPR are primarily responsible for maintaining the pressor response during isometric exercise. This highlights the relative importance of TPR compared to CO in mediating the pressor response during isometric exercise.

Abstract Exposure to extreme cold environments is potentially life‐threatening. However, the world record holder of full‐body ice immersion has repeatedly demonstrated an extraordinary tolerance to extreme cold. We aimed to explore thermoregulatory, metabolic, and cardiovascular responses during 88 min of full‐body ice immersion. We continuously measured gastrointestinal temperature (Tgi), skin temperature (Tskin), blood pressure, and heart rate (HR). Oxygen consumption (VO2) was measured at rest, and after 45 and 88 min of ice immersion, in order to calculate the metabolic heat production. Tskin dropped significantly (28–34°C to 4–15°C) and VO2 doubled (5.7–11.3 ml kg−1 min−1), whereas Tgi (37.6°C), HR (72 bpm), and mean arterial pressure (106 mmHg) remained stable during the first 30 min of cold exposure. During the remaining of the trial, Tskin and VO2 remained stable, while Tgi gradually declined to 37.0°C and HR and mean arterial blood pressure increased to maximum values of 101 bpm and 115 mmHg, respectively. Metabolic heat production in rest was 169 W and increased to 321 W and 314 W after 45 and 80 min of ice immersion. Eighty‐eight minutes of full‐body ice immersion resulted in minor changes of Tgi and cardiovascular responses, while Tskin and VO2 changed markedly. These findings may suggest that our participant can optimize his thermoregulatory, metabolic, and cardiovascular responses to challenge extreme cold exposure.

Background Low‐grade inflammation, largely mediated by monocyte‐derived macrophages, contributes to atherosclerosis. Sedentary behavior is associated with atherosclerosis and cardiovascular diseases (CVD). We examined whether reducing sedentary behavior and improving walking time improves monocyte inflammatory phenotype in subjects with increased cardiovascular risk. Methods and Results Across 2 waves, 16 individuals with increased cardiovascular risk performed a 16‐week intervention study (age 64±6 years, body mass index 29.9±4.3 kg/m2), using a device with vibration feedback to promote physical activity. Before and after intervention, we objectively examined physical activity (ActivPAL), cytokine production capacity after ex vivo stimulation in peripheral blood mononuclear cells, metabolism of peripheral blood mononuclear cells, circulating cytokine concentrations, and monocyte immunophenotype. Overall, no significant increase in walking time was found (1.9±0.7 to 2.2±1.2 h/day, P=0.07). However, strong, inverse correlations were observed between the change in walking time and the change in production of interleukin (IL)‐1β, IL‐6, IL‐8, and IL‐10 after lipopolysaccharide stimulation (rs=−0.655, −0.844, −0.672, and −0.781, respectively, all P

Abstract Breaking up prolonged sitting with physical activity (PA) breaks prevents conduit artery dysfunction. However, the optimal break strategy to achieve this, in terms of the frequency or duration of PA, is not known. This study assessed the effect of breaking up sitting with different PA break strategies on lower limb peripheral artery endothelial function. Fifteen participants (10 male, 35.8 ± 10.2 years, BMI: 25.5 ± 3.2 kg m−2) completed, on separate days, three 4‐h conditions in a randomized order: (1) uninterrupted sitting (SIT), (2) sitting with 2‐min light‐intensity walking breaks every 30 min (2WALK), or (3) sitting with 8‐min light‐intensity walking breaks every 2 h (8WALK). At baseline and 4 h, superficial femoral artery function (flow‐mediated dilation; FMD), blood flow, and shear rate (SR) were assessed using Doppler ultrasound. For each condition, the change in outcome variables was calculated and data were statistically analyzed using a linear mixed model. There was no significant main effect for the change in FMD (P = 0.564). A significant main effect was observed for the change in blood flow (P = 0.022), with post hoc analysis revealing a greater reduction during SIT (−42.7 ± 14.2 mL·min) compared to 8WALK (0.45 ± 17.7 mL·min; P = 0.012). There were no significant main effects for mean, antegrade, or retrograde SR (P > 0.05). Superficial femoral artery blood flow, but not FMD, was reduced following uninterrupted sitting. This decline in blood flow was prevented with longer duration, less frequent walking breaks rather than shorter, more frequent breaks suggesting the dose (duration and frequency) of PA may influence the prevention of sitting‐induced decreases in blood flow.

Introduction: Reperfusion is required to salvage ischaemic tissue, but also causes further damage (i.e., ischaemia/reperfusion-injury). Heart failure patients reveal exaggerated ischaemia/reperfusion-injury, whilst traditional ischaemic preconditioning cannot prevent ischaemia/reperfusion-injury. Exercise training may be a more powerful preconditioning stimulus, especially high-intensity interval training given the similarities with ischaemic preconditioning. Therefore, we examined the impact of 12-week continuous training vs. high-intensity interval training on brachial artery endothelial ischaemia/reperfusion-injury in heart failure patients New York Heart Association-class II-III.Methods: Twenty heart failure patients (male:female 19:1, 64 ± 8 years, ejection fraction 38 ± 6%) were allocated to 12-weeks of high-intensity interval training (10∗1-min 90% maximal workload – 2.5-min 30% maximal workload) or continuous training (30-min 60–75% maximal workload). Before and after the intervention, we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after ischaemia/reperfusion (5-min ischemic exercise, 15-min reperfusion).Results: Ischaemia/reperfusion caused a significant decline in FMD (continuous training (n = 10): 5.2 ± 2.5 to 3.4 ± 1.6%, high-intensity interval training (n = 10): 5.3 ± 2.6 to 3.5 ± 1.6%, P = 0.01), which was not different between groups (P > 0.05). Training improved maximal workload and fitness (P < 0.05), with no differences between groups (P > 0.05). Exercise training did not alter FMD (P > 0.05), whilst ischaemia/reperfusion did not impair FMD after exercise training (continuous training: 4.8 ± 3.0 to 4.2 ± 2.3%, high-intensity interval training: 4.7 ± 2.5 to 3.8 ± 2.3%, P > 0.05). No changes were found in FMD before or after ischaemia/reperfusion after 12-weeks in controls (n = 9).Conclusion: We found that 12-week exercise training in heart failure patients mitigated endothelial ischaemia-reperfusion injury, an effect independent of the type of exercise. These changes may contribute to the cardioprotective effects of exercise training, whilst our findings highlight the potency of exercise as a preconditioning stimulus.

Background Premenopausal women have a lower incidence of cardiovascular disease, which may partly be due to a protective effect of estrogen on endothelial function. Animal studies suggest that estrogen may also improve the relationship between shear rate (SR) and endothelial function. We aimed to explore the relationship between endothelial function (ie, flow‐mediated dilation [FMD]) and SR (ie, SR area under the curve [SRAUC]) in women versus men, and between pre‐ versus postmenopausal women. Methods and Results Brachial artery FMD and SRAUC were measured in accordance with expert‐consensus guidelines in 932 healthy participants who were stratified into young adults (18‐40 years, 389 men, 144 women) and older adults (>40 years, 260 men, 139 women). Second, we compared premenopausal (n=173) and postmenopausal women (n=110). There was evidence of a weak correlation between SRAUC and FMD in all groups but older men, although there was variation in strength of outcomes. Further exploration using interaction terms (age‐sex×SRAUC) in linear regression revealed differential relationships with FMD (young women versus young men [β=−5.8−4, P=0.017] and older women [β=−5.9−4, P=0.049]). The correlation between SRAUC and FMD in premenopausal women (r2=0.097) was not statistically different from that in postmenopausal women (r2=0.025; Fisher P=0.30). Subgroup analysis using stringent inclusion criteria for health markers (n=505) confirmed a stronger FMD‐SRAUC correlation in young women compared with young men and older women. Conclusions Evidence for a stronger relationship between endothelial function and the eliciting SR stimulus is present in young women compared with men. Estrogen may contribute to this finding, but larger healthy cohorts are required for conclusive outcomes.

Introduction: The ability of ischemic preconditioning (IPC) to enhance exercise capacity may be mediated through altering exercise-induced blood flow and/or vascular function. This study investigated the hypothesis that (local) IPC enhances exercise-induced blood flow responses and prevents decreases in vascular function following exercise.Methods: Eighteen healthy, recreationally trained, male participants (mean ±SD: age 32 ± 8 years; BMI 24.2 ± 2.3; blood pressure 122 ± 10/72 ± 8 mmHg; resting HR 58 ± 9 beats min-1) received IPC (220 mmHg; 4 × 5-min bilateral arms), REMOTE IPC (220 mmHg; 4 × 5-min bilateral legs), or SHAM (20 mmHg; 4 × 5-min bilateral arms) in a counterbalanced order prior to 30-min of submaximal (25% maximal voluntary contraction) unilateral rhythmic handgrip exercise. Brachial artery diameter and blood flow were assessed every 5-min throughout the 30-min submaximal exercise using high resolution ultrasonography. Pre- and post-exercise vascular function was measured using flow-mediated dilation (FMD).Results: IPC resulted in enlarged brachial artery diameter during exercise [0.016 cm (0.003–0.03 cm), P = 0.015] compared to REMOTE IPC, but blood flow during exercise was similar between conditions (P > 0.05). Blood flow (l/min) increased throughout exercise (time: P < 0.005), but there was no main effect of condition (P = 0.29) or condition ∗ time interaction (P = 0.83). Post-exercise FMD was similar between conditions (P > 0.05).Conclusion: Our data show that local (but not remote) IPC, performed as a strategy prior to exercise, enhanced exercise-induced conduit artery diameter dilation, but these changes do not translate into increased blood flow during exercise nor impact post-exercise vascular function.