Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.

Letter to the editor: fasting decreases expression of microRNAs linked to endothelial pathophysiology in mononuclear cells of healthy subjects.

This study explores how 14-15 h fasting or acute exercise affects immune cell epigenetics, specifically focusing on miRNAs in mononuclear cells. Findings suggest fasting significantly impacts microRNAs associated with endothelial metabolism compared to exercise, but does not directly connect these changes to cell apoptosis or autophagy. This enhances comprehension of cellular self-consumption under health-promoting interventions.

Effects of high-intensity interval training on retinal vessel diameters and oxygen saturation in patients with hypertension: A cross-sectional and randomized controlled trial.

INTRODUCTION: Arterial hypertension is a global healthcare burden that affects macrovascular and microvascular structure and function and can promote vascular end-organ damage. This study aimed 1) to evaluate differences in microvascular health between normotensive individuals and patients with arterial hypertension and 2) to assess the effects of short-term high-intensity interval training (HIIT) on microvascular health in the subgroup with arterial hypertension as add-on treatment to antihypertensive medication. METHODS: In the cross-sectional part, central retinal arteriolar (CRAE) and venular diameter equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), and retinal oxygen saturation (O2-saturation) were investigated in 19 normotensive healthy controls (mean age 56 ± 7 years) and 41 patients with arterial hypertension (mean age 59 ± 7 years). In the subsequent randomized controlled trial (RCT), patients with arterial hypertension were randomized to an intervention group (HIIT 3×/week) or a control group that received standard physical activity recommendations after baseline assessment. Assessments of retinal vessel biomarkers and patients` characteristics were repeated after the intervention period of 8 weeks. RESULTS: In the cross-sectional part, individuals with normal blood pressure (BP) showed lower body mass index (BMI), body fat, 24 h systolic and diastolic BP, higher peak oxygen uptake, wider CRAE (174 ± 17 µm vs. 161 ± 17 µm, p = 0.009), and higher AVR (0.84 ± 0.05 vs. 0.79 ± 0.05, p = 0.003) compared to patients with hypertension. In the RCT, patients with arterial hypertension showed reduced BMI and fasting glucose levels after HIIT and control condition. In addition, the intervention group reduced body fat percentage (27.0 ± 5.5 vs. 25.8 ± 6.1, p = 0.023) and increased peak oxygen uptake (33.3 ± 5.7 vs. 36.7 ± 5.1, p < 0.001). No changes in BP were found in either group. The intervention group showed narrower CRVE (ß -4.8 [95 % CI, -8.85, -0.81] p = 0.020) and higher AVR (0.03 [0.01, 0.04] p < 0.001) after eight weeks of HIIT compared to the control group. No statistically significant changes in retinal O2-saturation were found in either group. CONCLUSION: Short-term HIIT proved to be an effective treatment to ameliorate hypertension-induced retinal microvascular abnormalities in patients with hypertension. Retinal vessel diameters may prove to be a sensitive biomarker to quantify treatment efficacy at the microvascular level, at the earliest possible stage in patients with hypertension.

Exercise Therapy for Chronic Symptomatic Peripheral Artery Disease: A Clinical Consensus Document of the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases in Collaboration With the European Society of Vascular Medicine and the European Society for Vascular Surgery.

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Lower extremity physical function and quality of life in patients with stroke: a longitudinal cohort study.

PURPOSE: Lower extremity physical function (LEPF) is a key component for mobility and is impacted in stroke-related disability. A reduction in LEPF can have a significant impact on an individual's Quality of Life (QoL). The aim of this study is to characterise the relationship between LEPF and QoL. METHODS: The MOBITEC-Stroke Study is a longitudinal cohort-study including patients with their first occurrence of ischaemic stroke. Using a linear mixed-effects model, the relationship between LEPF (timed up-and-go performance (TUG); predictor) and QoL (Stroke Specific Quality of Life scale (SS-QoL); outcome) at 3 and 12 months post stroke was investigated and adjusted for sex, age, Instrumental Activities of Daily Living (IADL), fear of falling (Falls Efficacy Scale-International Version, FES-I), and stroke severity (National Institute of Stroke Severity scale, NIHSS), accounting for the repeated measurements. RESULTS: Data of 51 patients (65 % males, 35% females) were analysed. The mean age was 71.1 (SD 10.4) years, median NIHSS score was 2.0. SS-QoL was 201.5 (SD 20.5) at 3 months and 204.2 (SD 17.4) at 12 months; the mean change was 2.7 (95% CI -2.4 to 7.7), p= 0.293. A positive association was found between baseline TUG performance (estimate log score -13.923; 95% CI -27.495 to -0.351; p=0.048) and change in SS-QoL score in multivariate regression analysis. CONCLUSION: Higher LEPF (i.e better TUG performance) at baseline, was associated with an improvement in QoL from 3- to 12-months post stroke. These results highlight the critical role of physical function, particularly baseline LEPF, in influencing the QoL of stroke survivors.

A verification phase adds little value to the determination of maximum oxygen uptake in well-trained adults.

PURPOSE: The objective was to investigate if performing a sub-peak or supra-peak verification phase following a ramp test provides additional value for determining 'true' maximum oxygen uptake ( V ˙ O2). METHODS: 17 and 14 well-trained males and females, respectively, performed two ramp tests each followed by a verification phase. While the ramp tests were identical, the verification phase differed in power output, wherein the power output was either 95% or 105% of the peak power output from the ramp test. The recovery phase before the verification phase lasted until capillary blood lactate concentration was ≤ 4 mmol·L-1. If a V ˙ O2 plateau occurred during ramp test, the following verification phase was considered to provide no added value. If no V ˙ O2 plateau occurred and the highest V ˙ O2 ( V ˙ O2peak) during verification phase was < 97%, between 97 and 103%, or > 103% of V ˙ O2peak achieved during the ramp test, no value, potential value, and certain value were attributed to the verification phase, respectively. RESULTS: Mean (standard deviation) V ˙ O2peak during both ramp tests was 64.5 (6.0) mL·kg-1·min-1 for males and 54.8 (6.2) mL·kg-1·min-1 for females. For the 95% verification phase, 20 tests showed either a V ˙ O2 plateau during ramp test or a verification V ˙ O2peak < 97%, indicating no value, 11 showed potential value, and 0 certain value. For the 105% verification phase, the values were 26, 5, and 0 tests, respectively. CONCLUSION: In well-trained adults, a sub-peak verification phase might add little value in determining 'true' maximum V ˙ O2, while a supra-peak verification phase adds no value.

Exercise therapy for chronic symptomatic peripheral artery disease.

All guidelines worldwide strongly recommend exercise as a pillar in the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended to promote and assist the set up of comprehensive exercise programmes and best advice for patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are described based on the current best evidence. The document ends by highlighting supervised exercise programme access disparities across Europe and the evidence gaps requiring further research.

Omic-Scale High-Throughput Quantitative LC-MS/MS Approach for Circulatory Lipid Phenotyping in Clinical Research.

Lipid analysis at the molecular species level represents a valuable opportunity for clinical applications due to the essential roles that lipids play in metabolic health. However, a comprehensive and high-throughput lipid profiling remains challenging given the lipid structural complexity and exceptional diversity. Herein, we present an 'omic-scale targeted LC-MS/MS approach for the straightforward and high-throughput quantification of a broad panel of complex lipid species across 26 lipid (sub)classes. The workflow involves an automated single-step extraction with 2-propanol, followed by lipid analysis using hydrophilic interaction liquid chromatography in a dual-column setup coupled to tandem mass spectrometry with data acquisition in the timed-selective reaction monitoring mode (12 min total run time). The analysis pipeline consists of an initial screen of 1903 lipid species, followed by high-throughput quantification of robustly detected species. Lipid quantification is achieved by a single-point calibration with 75 isotopically labeled standards representative of different lipid classes, covering lipid species with diverse acyl/alkyl chain lengths and unsaturation degrees. When applied to human plasma, 795 lipid species were measured with median intra- and inter-day precisions of 8.5 and 10.9%, respectively, evaluated within a single and across multiple batches. The concentration ranges measured in NIST plasma were in accordance with the consensus intervals determined in previous ring-trials. Finally, to benchmark our workflow, we characterized NIST plasma materials with different clinical and ethnic backgrounds and analyzed a sub-set of sera (n = 81) from a clinically healthy elderly population. Our quantitative lipidomic platform allowed for a clear distinction between different NIST materials and revealed the sex-specificity of the serum lipidome, highlighting numerous statistically significant sex differences.

Circulating Gal-3 and sST2 are associated with acute exercise-induced sustained endothelial activation: Possible relevance for fibrosis development?

Long-term, intense endurance exercise training can occasionally induce endothelial micro-damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well-trained male participants (10 runners and 10 cyclists) performed a strenuous high-intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal-3 and sST2 concentrations were investigated by enzyme-linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal-3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal-3 and sST2 concentrations both showed a positive relationship with ECs (rrm  = 0.68, P = 0.001 and rrm  = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal-3 was significant only in cyclists, but equally strong for both modalities. Gal-3 was also related to exercise-induced CTi (rrm  = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise-released Gal-3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise-induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long-term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. NEW FINDINGS: What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal-3 is an enhanced cardiac contractility. Acute exercise-released Gal-3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

Effect of lifestyle interventions on carotid arterial structure - The DR's EXTRA study.

No lifestyle-based interventions with medium-term duration on carotid atherosclerotic have been performed so far. We aimed to investigate whether guideline-based dietary and physical activity interventions slow the progression of atherosclerotic changes in the general elderly population. 1410 Finnish men and women from a representative population sample were randomly assigned to one of six groups in the four-year intervention study: 1) reference, 2) aerobic training, 3) resistance training, 4) Nordic Diet, 5) aerobic training + Nordic Diet, 6) resistance training + Nordic Diet. The primary outcome was mean common carotid artery intima-media thickness (cIMT). The lumen diameter of the common carotid artery (cLD) was also analyzed. 567 men and 565 women aged 57 to 78 years were included. None of the intervention groups significantly slowed cIMT progression compared to the reference group. A subgroup analysis showed that men in the diet group had significantly smaller cIMT progression than in the reference group (-0.078 mm, 95% CI: -0.146 to -0.009, p = 0.02) and no significant increase in cIMT (p = 0.23). No other group showed a slowed cIMT progression. Among guideline-based lifestyle interventions, only diet leads to a significantly smaller progression of cIMT in older men of a representative population sample. No other lifestyle intervention contributed to a slowing of the progression of structural carotid markers. It must be questioned whether the guideline-based recommendations for a lifestyle change that were in place until recently are adequate to decelerate the atherosclerotic process.

Skeletal muscle and heart failure - What is the relationship between central versus peripheral affections?

BACKGROUND AND AIM: Heart failure is considered as a systemic disease as beside the heart, skeletal muscle is affected. METHODS AND RESULTS: In this retrospective case-control study 64 men and 15 women with heart failure as well as an individually pairwise matched sample by sex, age and body mass index of healthy individuals from the COmPLETE cohort study performed an exhaustive cardiopulmonary exercise test, strength tests and anthropometric measurements. V̇O2peak was 28.6% lower in male and 24.6% lower in female patients with heart failure as compared to healthy controls. Strength parameters are significantly higher for counter movement jump in male subjects. In females, significant differences were detected for mid-thigh pull in healthy versus patients with heart failure. Skeletal muscle mass of patients was in male as well as female 3.7% lower than in controls. Furthermore, the function of skeletal muscle seems impaired as the ability to accelerate is significantly lower in affected male with a heart pathology. CONCLUSION: It seems that severe affections (approx. 25 to 30%) on cardiocirculatory level are associated with moderate to low affections on functional and structural capacity on skeletal muscle level. Further, as in the male cohort with a heart pathology acceleration meaning 'fast' contracting is impaired, it is suggested, that the central limitations respectively the low perfusion of skeletal muscle over years yield to adaptions on muscle cell level ingoing with a decreased ability of fast contracting. It is therefore suggested, that the central circulatory limitations in patients with heart failure, respectively the low perfusion of skeletal muscle over years, promote maladaptation's in the periphery.

Short-term high-intensity interval training improves micro- but not macrovascular function in hypertensive patients.

INTRODUCTION: Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension. METHODS: Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks. RESULTS: Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group. CONCLUSION: Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future.

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Lymphocytes are less sensitive to autophagy than monocytes during fasting and exercise conditions.

The concomitant investigation of apoptosis (a regulated cell death) and autophagy (a conserved cell survival mechanism) in immune cells is rare. More detailed knowledge of these two types of self-consumption in circulating lymphocytes and monocytes would be important, since conditions such as fasting and acute exercise could promote health by a coordinated/linked modulation of autophagy and apoptosis in these mononuclear cells. In this study we performed flow cytometry to quantify numbers of apoptotic and autophagic mononuclear cells, lymphocytes and monocytes in fasting, standardized fed, and exercise conditions, using Annexin V, LC3B, and p62, respectively. We show that within total mononuclear cells lymphocytes are less apoptotic and autophagic than monocytes during fasting (p < 0.001, p < 0.05, respectively) and after acute exercise (p < 0.01, p < 0.05, respectively). Fasting increased circulating autophagic monocyte concentrations, but not lymphocytes compared to the fed control condition. Acute exercise elevated circulating autophagic lymphocyte concentrations, but not monocytes. Interestingly, Western blotting analysis of the fasting samples showed that higher LC3BII/I ratios were correlated with lower numbers of autophagic mononuclear cells (r = - 0.74, p = 0.02, n = 8), which could be attributed to the monocyte subgroup, but not lymphocytes. These results extend the current knowledge of the two types of self-consumption in circulating immune cells and underline their possible importance in pro-inflammatory monocytes during fasting and exercise as health promoting interventions.

Imagery ability assessments: a cross-disciplinary systematic review and quality evaluation of psychometric properties.

BACKGROUND: Over the last two centuries, researchers developed several assessments to evaluate the multidimensional construct of imagery. However, no comprehensive systematic review (SR) exists for imagery ability evaluation methods and an in-depth quality evaluation of their psychometric properties. METHODS: We performed a comprehensive systematic search in six databases in the disciplines of sport, psychology, medicine, education: SPORTDiscus, PsycINFO, Cochrane Library, Scopus, Web of Science, and ERIC. Two reviewers independently identified and screened articles for selection. COSMIN checklist was used to evaluate the methodological quality of the studies. All included assessments were evaluated for quality using criteria for good measurement properties. The evidence synthesis was summarised by using the GRADE approach. RESULTS: In total, 121 articles reporting 155 studies and describing 65 assessments were included. We categorised assessments based on their construct on: (1) motor imagery (n = 15), (2) mental imagery (n = 48) and (3) mental chronometry (n = 2). Methodological quality of studies was mainly doubtful or inadequate. The psychometric properties of most assessments were insufficient or indeterminate. The best rated assessments with sufficient psychometric properties were MIQ, MIQ-R, MIQ-3, and VMIQ-2 for evaluation of motor imagery ability. Regarding mental imagery evaluation, only SIAQ and VVIQ showed sufficient psychometric properties. CONCLUSION: Various assessments exist to evaluate an individual's imagery ability within different dimensions or modalities of imagery in different disciplines. However, the psychometric properties of most assessments are insufficient or indeterminate. Several assessments should be revised and further validated. Moreover, most studies were only evaluated with students. Further cross-disciplinary validation studies are needed including older populations with a larger age range. Our findings allow clinicians, coaches, teachers, and researchers to select a suitable imagery ability assessment for their setting and goals based on information about the focus and quality of the assessments. SYSTEMATIC REVIEWS REGISTER: PROSPERO CRD42017077004 .

Microvascular endothelial dysfunction in heart failure patients: An indication for exercise treatment?

BACKGROUND: Endothelial dysfunction represents a diagnostic marker to differentiate disease severity in chronic heart failure (CHF) patients. Retinal vessel phenotyping was applied in CHF patients as it has been acknowledged as a sensitive diagnostic tool to quantify microvascular health and overall cardiovascular risk. METHODS: The central retinal arteriolar (CRAE) and venular diameter equivalents (CRVE) as well as the retinal microvascular function, quantified by arteriolar (aFID) and venular flicker-light induced dilatation (vFID), were analyzed in 26 CHF patients. These data were compared with 26 age- and sex-matched healthy peers. The effects of an exercise intervention on retinal microvascular health in one CHF patient were investigated to demonstrate potentially beneficial effects of exercise treatment in a case report format as proof of concept. RESULTS: CHF patients showed narrower CRAE (170 ± 16 µm vs. 176 ± 16 µm, p = 0.237) and wider CRVE (217 ± 20 µm vs. 210 ± 17 µm, p = 0.152), resulting in a significantly lower arteriolar-to-venular diameter ratio (AVR, 0.79 ± 0.07 vs. 0.84 ± 0.06, p = 0.004) compared to controls. More strikingly, CHF patients showed significantly lower mean aFID (1.24 ± 1.14% vs. 3.78 ± 1.85%, p < 0.001) and vFID (2.89 ± 1.33% vs. 3.88 ± 1.83%, p = 0.033). Twelve weeks of exercise therapy induced wider CRAE (143 ± 1.0 µm vs. 153 ± 0.9 µm), narrower CRVE (183 ± 3.1 µm vs. 180 ± 2.4 µm) and improved aFID (0.67% vs. 1.25%) in a male 78 years old CHF patient. CONCLUSIONS: aFID is a sensitive diagnostic tool to quantify microvascular impairments in CHF patients. Exercise treatment in CHF patients has high potential to improve retinal microvascular health as a marker for vascular regeneration and overall risk reduction, which warrants further examination by randomized controlled trials.

Association of blood pressure, obesity and physical activity with arterial stiffness in children: a systematic review and meta-analysis.

Central pulse wave velocity (cPWV) is a biomarker for cardiovascular (CV) risk and a predictor for CV events in adulthood. Alterations of arterial stiffness have also been associated with CV risk in childhood. The study aimed to systematically review and meta-analyze the association of blood pressure (BP), body mass index (BMI), and cardiorespiratory fitness (CRF) with cPWV in children. Literature search was through the databases PubMed, Web of Science, Embase and the Cochrane Register of Controlled Trials. Twenty-two articles were included in the systematic review and eight articles in the meta-analysis. Higher systolic and diastolic BP were associated with higher cPWV (pooled estimated effect size (ES) 0.02 (95% CI: 0.012-0.027; P < 0.001), and ES 0.02 (95% CI: 0.011-0.029; P < 0.001); respectively). Higher BMI correlated with higher cPWV (ES 0.025 (95% CI: 0.013-0.038; P < 0.001)). CRF was inversely associated with cPWV (ES -0.033 (95% CI: -0.055 to -0.011; P = 0.002)). In children, higher BP and BMI are already related to increased cPWV, and enhanced CRF may be a preventive strategy to counteract development of CV disease later in life. IMPACT: This meta-analysis suggests that elevated blood pressure and body mass index in childhood correlate with increased central pulse wave velocity. Children with higher cardiorespiratory fitness appear to have favorably lower arterial stiffening. Elevated blood pressure and altered arterial stiffness originate early in life and childhood risk stratification as well as timely initiation of exercise treatment may help counteract development of manifest cardiovascular disease later in life.

VascuFit: vascular effects of non-linear periodized exercise training in sedentary adults with elevated cardiovascular risk - protocol for a randomized controlled trial.

BACKGROUND: Early vascular aging (EVA) is increasingly prevalent in the general population. Exercise is important for primary cardiovascular prevention, but often insufficient due to ineffective training methods and a lack of biomarkers suitable to monitor its vascular effects. VascuFit will assess the effectiveness of non-linear periodized aerobic exercise (NLPE) in a non-athletic sedentary population to improve both established and promising biomarkers of EVA. METHODS: Forty-three sedentary adults, aged 40-60 years, with elevated cardiovascular risk will either engage in 8 weeks of ergometer-based NLPE (n = 28) or receive standard exercise recommendations (n = 15). The primary outcome will be the change of brachial-arterial flow-mediated dilation (baFMD) after versus before the intervention. Secondary outcomes will be the change in static vessel analysis (SVA; clinical biomarker of microvascular endothelial function), endomiRs (microRNAs regulating key molecular pathways of endothelial cell homeostasis) and circulating cellular markers of endothelial function (mature endothelial cells, endothelial progenitor cells). Tertiary outcomes will be the change in sphingolipidome, maximum oxygen capacity, and traditional cardiovascular risk factors (blood pressure, triglycerides, cholesterol, fasting glucose, high-sensitivity C-reactive protein). DISCUSSION: We expect an improvement of baFMD of at least 2.6% and significant pre-post intervention differences of SVA and endomiRs as well as of the tertiary outcomes in the intervention group. VascuFit may demonstrate the effectiveness of NLPE to improve endothelial function, thus vascular health, in the general sedentary population. Furthermore, this project might demonstrate the potential of selected molecular and cellular biomarkers to monitor endothelial adaptations to aerobic exercise. TRIAL REGISTRATION: The trial was registered on www. CLINICALTRIALS: gov (NCT05235958) in February 11th 2022.

Lipoprotein Subclasses Independently Contribute to Subclinical Variance of Microvascular and Macrovascular Health.

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

Psychometric properties of the MOBITEC-GP mobile application for real-life mobility assessment in older adults.

Aim of this study was to test the reliability and validity of the life-space measures and walking speed delivered by the MOBITEC-GP app. Participants underwent several supervised walking speed assessments as well as a 1-week life-space assessment during two assessment sessions 9 days apart. Fifty-seven older adults (47.4% male, mean age= 75.3 (±5.9) years) were included in the study. The MOBITEC-GP app showed moderate to excellent test-retest reliability (ICCs between 0.584 and 0.920) and validity (ICCs between 0.468 and 0.950) of walking speed measurements of 50 meters and above and of most 1-week life-space parameters, including life-space area, time spent out-of-home, and action range. The MOBITEC-GP app for Android is a reliable and valid tool for the assessment of real-life walking speed (at distances of 50 metres and above) and life-space parameters of older adults. Future studies should look into technical issues more systematically in order to avoid invalid measurements.