Subcutaneous advanced glycation end products, cardiovascular risk factors and vascular health during childhood development in a Swiss population.

Background: Skin-derived advanced glycation end products (sAGEs) have been associated with cardiovascular (CV) risk and mortality in adults. We hypothesize that cardiorespiratory fitness (CRF), body mass index (BMI) and vascular health are associated with development of sAGEs during childhood. Methods: In our prospective cohort study, 1171 children aged 6-8 years were screened for sAGEs, BMI, retinal arteriolar diameters (CRAE) and pulse wave velocity (PWV), using standardized procedures. To determine CRF a 20 m shuttle run was performed. After four 4 years, all parameters were assessed in 675 children using the same protocols. Results: Higher initial CRF levels were significantly associated with lower sAGEs (ß [95 CI] -0.02 [-0.03 to -0.002] au, p = 0.022) levels at follow-up, although they showed a greater change from baseline to follow-up (ß [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (ß [95% CI] -5.42 [-8.76 to -2.08] µm, p = 0.001) at follow-up and showed a greater change in CRAE (ß [95% CI] -3.99 [-7.03 to -0.96] µm, p = 0.010) from baseline to follow-up. Conclusion: Exercise and higher CRF may help mitigate the formation of AGEs during childhood, thereby reducing the risk for development of CV disease associated with AGEs-induced damage. Preventive strategies may need to target CRF early in life to achieve improvement of CV risk factors and may counteract the development of CV disease later in life.

Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

INTRODUCTION: Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. METHODS: This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. TRIAL REGISTRATION: The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023.

Accelerometer Metrics: Healthy Adult Reference Values, Associations with Cardiorespiratory Fitness, and Clinical Implications.

PURPOSE: Accelerometer-assessed physical activity (PA) can be summarized using cut-point-free or population-specific cut-point-based outcomes. We aimed to 1) examine the interrelationship between cut-point-free (intensity gradient (IG) and average acceleration (AvAcc)) and cut-point-based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point-free metrics to that with cut-point-based metrics in healthy adults aged 20 to 89 yr and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults. METHODS: In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their nondominant wrist and underwent cardiopulmonary exercise testing. Cut-point-free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The "interpretablePA" R-package was developed to translate findings into clinical practice. RESULTS: IG and AvAcc yield complementary information on PA with both IG ( P = 0.009) and AvAcc ( P < 0.001) independently associated with CRF in healthy individuals (adjusted R2 = 73.9%). Only IG was independently associated with CRF in patients with heart failure ( P = 0.043, adjusted R2 = 38.4%). The best cut-point-free and cut-point-based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults. CONCLUSIONS: IG and AvAcc are strongly associated with CRF and thus indirectly with the risk of noncommunicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point-based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point-free metrics in clinical practice.

Cardiorespiratory fitness and development of childhood cardiovascular risk: The EXAMIN YOUTH follow-up study.

Background: Obesity- and hypertension-related cardiovascular (CV) risk has been shown to originate in childhood. Higher body mass index (BMI) and blood pressure (BP) have been associated with increased large artery stiffness and a lower microvascular arteriolar-to-venular diameter ratio (AVR) in children. This study aimed to investigate the association of cardiorespiratory fitness (CRF) with development of BMI, BP and vascular health during childhood. Methods: In our prospective cohort study, 1,171 children aged 6-8 years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20 m shuttle run test. After 4 years, all parameters were assessed in 664 children using the same protocols. Results: Children with a higher CRF at baseline developed a significantly lower BMI (ß [95% CI] -0.09 [-0.11 to -0.06] kg/m2, p < 0.001), a lower systolic BP (ß [95% CI] -0.09 [-0.15 to -0.03] mmHg, p = 0.004) and a higher AVR (ß [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4 years. The indirect association of CRF with development of retinal arteriolar diameters was mediated by changes in BMI. Conclusion: Our results identify CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in children. Obesity-related CV risk has been shown to track into adulthood, and achieving higher CRF levels in children may help counteract the development of CV risk and disease not only in pediatric populations, but may also help reduce the burden of CVD in adulthood. Registration: http://www.clinicaltrials.gov/ (NCT02853747).

Bivariate relation of vascular health and blood pressure progression during childhood.

BACKGROUND AND AIMS: Hypertension is a major risk factor for the development of cardiovascular disease (CVD) in adulthood. High blood pressure (BP) is associated with subclinical vascular impairments as early as childhood. We aimed to assess the association of retinal microvascular diameters and large artery pulse wave velocity (PWV) with progression of childhood BP. METHODS: In our prospective Basel cohort study, 1171 children aged 6-8 years were screened for BP, body mass index, retinal vessel diameters and PWV using standardized protocols. After 4 years, all parameters were assessed in 749 children using the same protocols. RESULTS: Children with narrower central retinal arteriolar diameters (CRAE) and higher PWV at baseline developed higher systolic BP after 4 years (ß [95% CI] 0.6 [0.072 to 1.164] mmHg per 10 µm decrease, p = 0.026 and ß [95% CI] 0.6 [0.331 to 0.838] mmHg per 0.1 m/s increase, p < 0.001, respectively). Children with increased systolic BP at baseline developed narrower CRAE and higher PWV at follow-up (ß [95% CI] -3.3 [-4.43 to -2.09] µm per 10 mmHg increase, p < 0.001 and ß [95% CI] 0.13 [0.10 to 0.16] m/s per 10 mmHg increase, p < 0.001, respectively). CONCLUSIONS: Retinal arteriolar diameter and PWV independently predict progression of childhood BP, while initial BP is linked to development of micro- and macrovascular impairments, describing a bivariate temporal relationship between vascular health and BP. Childhood may present a window of opportunity for initiation of primary prevention strategies for the treatment of high BP to help prevent manifestation of CVD later in life.

Prospective associations of physical fitness with spinal flexibility in childhood: implications for primary prevention of non-specific back pain.

Objectives: Early predictors for back pain need to be identified for the development of prevention strategies starting as early as childhood. For this purpose, the relationship between physical fitness and spinal flexibility at the age of six years and its prediction for the development of non-specific back pain (BP) during childhood were analyzed. Methods: In this prospective cohort study with 4-year follow-up, school children from the Swiss Canton Basel-Stadt, aged 6-8 (2014) at baseline and 10-12 years (2018) at follow-up, were recruited from 26 primary schools (n = 238) within a mandatory evaluation of motor skills. Data for spinal flexibility were collected by use of a hand-held computer-assisted device and physical fitness was assessed by shuttle run performance at both time points. Occurrence of non-specific BP was determined by use of a questionnaire at follow-up. Results: Children with higher physical fitness at baseline achieved a better spinal flexibility four years later (ß [95% CI] 3.75 [2.19-5.3] degree per 1 stage increase, p < 0.001). Higher spinal flexibility by 1 degree at baseline was associated with 2% less odds for non-specific BP at follow-up (OR [95% CI] 0.98 [0.97-0.99] per 1 degree increase, p = 0.032). There was little evidence for a direct association between physical fitness at baseline and development of non-specific BP at follow-up (OR [95% CI] 1.13 [0.96-1.34] per 1 stage increase, p = 0.128). Conclusion: Fitness performance is associated with the development of better childhood spinal flexibility over four years. Moreover, a better spinal flexibility at baseline was associated with less non-specific BP at follow-up. This study suggests that physical fitness may be a key modulator of spinal flexibility which itself is a main determinant of non-specific BP during childhood development. Further long-term studies are warranted to confirm our assumptions and to prove trajectories into adolescents and adulthood.

Self-reported life-space mobility in the first year after ischemic stroke: longitudinal findings from the MOBITEC-Stroke project.

BACKGROUND: Life-space mobility is defined as the size of the area in which a person moves about within a specified period of time. Our study aimed to characterize life-space mobility, identify factors associated with its course, and detect typical trajectories in the first year after ischemic stroke. METHODS: MOBITEC-Stroke (ISRCTN85999967; 13/08/2020) was a cohort study with assessments performed 3, 6, 9 and 12 months after stroke onset. We applied linear mixed effects models (LMMs) with life-space mobility (Life-Space Assessment; LSA) as outcome and time point, sex, age, pre-stroke mobility limitation, stroke severity (National Institutes of Health Stroke Scale; NIHSS), modified Rankin Scale, comorbidities, neighborhood characteristics, availability of a car, Falls Efficacy Scale-International (FES-I), and lower extremity physical function (log-transformed timed up-and-go; TUG) as independent variables. We elucidated typical trajectories of LSA by latent class growth analysis (LCGA) and performed univariate tests for differences between classes. RESULTS: In 59 participants (mean age 71.6, SD 10.0 years; 33.9% women), mean LSA at 3 months was 69.3 (SD 27.3). LMMs revealed evidence (p ≤ 0.05) that pre-stroke mobility limitation, NIHSS, comorbidities, and FES-I were independently associated with the course of LSA; there was no evidence for a significant effect of time point. LCGA revealed three classes: "low stable", "average stable", and "high increasing". Classes differed with regard to LSA starting value, pre-stroke mobility limitation, FES-I, and log-transformed TUG time. CONCLUSION: Routinely assessing LSA starting value, pre-stroke mobility limitation, and FES-I may help clinicians identify patients at increased risk of failure to improve LSA.

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.

Timed up-and-go performance is associated with objectively measured life space in patients 3 months after ischemic stroke: a cross-sectional observational study.

BACKGROUND: Stroke is a common cause of mobility limitation, including a reduction in life space. Life space is defined as the spatial extent in which a person moves within a specified period of time. We aimed to analyze patients' objective and self-reported life space and clinical stroke characteristics. METHODS: MOBITEC-Stroke is a prospective observational cohort study addressing poststroke mobility. This cross-sectional analysis refers to 3-month data. Life space was assessed by a portable tracking device (7 consecutive days) and by self-report (Life-Space Assessment; LSA). We analysed the timed up-and-go (TUG) test, stroke severity (National Institutes of Health Stroke Scale; NIHSS), and the level of functional outcome (modified Rankin Scale; mRS) in relation to participants' objective (distance- and area-related life-space parameters) and self-reported (LSA) life space by multivariable linear regression analyses, adjusted for age, sex, and residential area. RESULTS: We included 41 patients, mean age 70.7 (SD11.0) years, 29.3% female, NIHSS score 1.76 (SD1.68). We found a positive relationship between TUG performance and maximum distance from home (p = 0.006), convex hull area (i.e. area enclosing all Global Navigation Satellite System [GNSS] fixes, represented as a polygon linking the outermost points; p = 0.009), perimeter of the convex hull area (i.e. total length of the boundary of the convex hull area; p = 0.008), as well as the standard ellipse area (i.e. the two-dimensional ellipse containing approximately 63% of GNSS points; p = 0.023), in multivariable regression analyses. CONCLUSION: The TUG, an easily applicable bedside test, seems to be a useful indicator for patients' life space 3 months poststroke and may be a clinically useful measure to document the motor rehabilitative process.

Norm Values of Muscular Strength Across the Life Span in a Healthy Swiss Population: The COmPLETE Study.

BACKGROUND: Grip strength is used to estimate whole-body strength for health surveillance purposes. Explosive strength is considered important, yet economic measures able to detect early deterioration of neuromuscular capabilities are lacking. Whether handgrip maximum rate of force development (GRFD) or whole-body strength tests are better predictors of lower body power than handgrip maximum strength (GFmax) and their trajectories throughout the life span are unknown. HYPOTHESIS: GRFD should be more closely related to lower body power than GFmax, and its trajectories over the life span should more closely follow that of lower body power. STUDY DESIGN: Cross-sectional. LEVEL OF EVIDENCE: Level 2b. METHODS: A total of 613 healthy participants aged 20 to 91 years were tested for countermovement jump peak power, GFmax, handgrip rate of force development, and midthigh pull peak force (MTP). Cubic splines and linear models were built for age trajectories, generalized additive models for quintile curves, and linear regression was used to assess predictive quality. RESULTS: Peak power (Pmax) declined linearly to 60% of young adult level, with GRFD, GFmax, and MTP remaining stable up to age 50 years and then declining more sharply to 52% to 71% of young adult levels. Trajectories were similar for male and female participants. GRFD (ß = 0.17) and MTP (ß = 0.08) were worse predictors of Pmax than GFmax (ß = 0.24) in models adjusted for age, sex, lean body mass, and vigorous physical activity levels. CONCLUSION: GRFD was not superior to maximum strength in predicting lower body power. For health surveillance purposes, it therefore appears that GFmax tests are more economical and equally good predictors of lower body explosive strength at older age. The data provided can be used as norm values for healthy subjects. CLINICAL RELEVANCE: Incorporating countermovement jump testing for early detection of declines in explosive capabilities might be advised.

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.

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.

Adherence to Life's simple 7 is associated with better carotid properties.

BACKGROUND AND AIMS: Cardiovascular health scores have emerged as a simple way to assess the risk to suffer from a cardiovascular disease. The American Heart Association's Life's Simple 7 constitutes of modifiable lifestyle factors to reduce cardiovascular risk. Its association with carotid properties is yet inconclusive. The aim of this study is to determine the association between the adherence to Life's Simple 7 and carotid properties in middle-aged to elderly Finns. METHODS: A representative sample of Finnish men and women aged 55-74 years was included in the present study. Carotid intima-media thickness (cIMT), lumen diameter (cLD), and carotid distensibility were measured by transcutaneous ultrasound using state-of-the-art wall contour detection techniques. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body mass index, cholesterol, systolic blood pressure, fasting plasma glucose, smoking status, physical activity, and diet). In accordance to the American Heart Association, for each category, an ideal score was given 2 points, intermediate scores 1 point, and poor scores 0 points. RESULTS: In total, 1400 (49.4% male) subjects were included in the analyses. After adjusting for age and sex, we found that subjects with a an ideal cardiovascular health score had lower cLD than those with an intermediate score (-0.21 mm, 95% CI: 0.37 to -0.05 mm, p=0.005) and a poor score (-0.39 mm, 95% CI: 0.65 to -0.12 mm, p=0.001). Similarly, subjects with an ideal health score had higher carotid distensibility than those with an intermediate score (0.0032 1/kPa, 95% CI: 0.009-0.0055 1/kPa, p=0.002) and a poor score (0.0018 1/kPa, 95% CI: 0.0005-0.0032 1/kPa, p=0.004). We found no differences regarding cIMT. CONCLUSIONS: In middle-aged to elderly Finns, higher adherence to the Life's Simple 7 is associated with lower cLD and higher distensibility, but not with cIMT. Adherence to healthy lifestyle habits is therefore associated with better carotid structure and carotid function in middle-aged to elderly Finns.

Ideal Life's Simple 7 Score Relates to Macrovascular Structure and Function in the Healthy Population.

BACKGROUND: Cardiovascular health scores, such as Life's Simple 7 from the American Heart Association, and the assessment of arterial properties are independently used to determine cardiovascular risk. However, evidence of their association remains scarce, especially in healthy, middle-aged to older populations. METHODS: A healthy sample of the Swiss population aged 50-91 years as part of the COmPLETE cohort study was included. Carotid intima-media thickness (cIMT), carotid lumen diameter (cLD), carotid distensibility coefficient (DC), flow-mediated dilation (FMD), and brachial-ankle pulse wave velocity (baPWV) were used to determine arterial properties. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body-mass index, cholesterol, systolic blood pressure, hemoglobin A1c, smoking status, physical activity, and diet). In accordance with the American Heart Association, for each category, two points were given for an ideal health metric level, intermediate scores one point, and poor scores zero points. Intermediate and ideal health scores corresponded to a total of 5-9 and 10-14 points, respectively. RESULTS: A total of 280 participants (50.7% male) were included. After adjusting for age and sex, an ideal health score was associated with lower cIMT (-0.038 mm, 95% CI: -0.069 mm--0.007 mm, p = 0.017), lower cLD (-0.28 mm, 95% CI: -0.46 mm--0.11 mm, p = 0.002), and lower baPWV (-0.05 m/s, 95% CI: -0.08 m/s--0.02 m/s, p = 0.003). No differences were found for FMD and DC. CONCLUSIONS: Even in a healthy sample of middle-aged and older adults, individuals with an ideal cardiovascular health score showed more favorable biomarkers of vascular aging than those with an intermediate score. This stresses the relevance of promoting an optimal lifestyle, even among the healthy population.

Association between arterial stiffness and walking capacity in older adults.

BACKGROUND AND AIM: Arterial stiffening - a process that is largely due to intimal thickening, collagen disposition or elastin fragmentation - significantly contributes to cardiovascular events and mortality. There is also some evidence that it may negatively affect physical function. This study aimed to evaluate whether arterial stiffness was associated with measures of walking capacity in a large, population-based sample of highly aged older adults. METHODS: A population-based sample of 910 community-dwelling adults (aged 75, 80, or 85 years) were investigated in a cross-sectional observational study. Pulse wave velocity (PWV), a surrogate marker of arterial stiffness, was estimated based on the oscillometric recording of pulse waves at the brachial artery site. Walking capacity was assessed by 10-meter habitual walking speed, 10-meter maximum walking speed, and six-minute walk distance. We used multiple linear regression models to examine possible associations between PWV and parameters of walking capacity, and we adjusted the models for sex, age, socioeconomic status, anthropometry, physician-diagnosed diseases, prescription medication, smoking history, physical activity, and mean arterial pressure. Continuous variables were modelled using restricted cubic splines to account for potential nonlinear associations. RESULTS: Mean (standard deviation) 10-meter habitual walking speed, 10-meter maximum walking speed, and six-minute walk distance were 1.3 (0.2) m/s, 1.7 (0.4) m/s, and 413 (85) m, respectively. The fully adjusted regression models revealed no evidence for associations between PWV and parameters of walking capacity (all p-values >0.05). CONCLUSION: Our results did not confirm previous findings suggesting a potential negative association between arterial stiffness and walking capacity in old age. Longitudinal studies, potentially taking additional confounders into account, are needed to disentangle the complex relationship between the two factors.

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.

Cardiorespiratory Fitness and Endothelial Function in Aging Healthy Subjects and Patients With Cardiovascular Disease.

Background: Individuals with a higher lifelong cardiorespiratory fitness show better vascular health with aging. Studies on fitness-related effects on endothelial function either analyzed samples with a narrow age-range or incompletely assessed endothelial responsiveness. This study aims to assess the impact of cardiorespiratory fitness on the association of brachial-arterial flow-mediated vasodilation (FMD) and low flow-mediated vasoconstriction (L-FMC) with age in healthy adults and patients with cardiovascular diseases. Methods: FMD, L-FMC and V . O2peak were prospectively measured in a population-based sample including 360 healthy adults and 99 patients with cardiovascular disease of European descend. Non-linear models were applied to assess V . O2peak-associated variations in age-related differences of endothelial function independent of classical cardiovascular risk factors. Results: FMD was negatively associated with age in healthy adults (adjusted R2 = 0.27, partial R2 = 0.07, p < 0.001) and in cardiovascular patients (adjusted R2 = 0.29, partial R2 = 0.05, p = 002). L-FMC showed no association with age. In models predicting the change of FMD with higher age, V . O2peak accounted for 2.8% of variation in FMD (χ2(5) = 5.37, p = 0.372, s = 1.43). Thereby, V . O2peak-stratified changes of FMD started to fan out at around 30 years of age in women and 50 years of age in men, with 7-12% lower values at old age with V . O2peak ≤3rd percentile compared to V . O2peak ≥97th percentile) in both, the healthy sample and in cardiovascular patients. Conclusion: The statistical effect of cardiorespiratory fitness on the association of FMD with age independent of classical cardiovascular risk factors was small in both, healthy aging adults as well as patients with cardiovascular diseases. Its clinical significance should be assessed further.

The Metabolic Signature of Cardiorespiratory Fitness: A Systematic Review.

BACKGROUND: Cardiorespiratory fitness (CRF) is a potent health marker, the improvement of which is associated with a reduced incidence of non-communicable diseases and all-cause mortality. Identifying metabolic signatures associated with CRF could reveal how CRF fosters human health and lead to the development of novel health-monitoring strategies. OBJECTIVE: This article systematically reviewed reported associations between CRF and metabolites measured in human tissues and body fluids. METHODS: PubMed, EMBASE, and Web of Science were searched from database inception to 3 June, 2021. Metabolomics studies reporting metabolites associated with CRF, measured by means of cardiopulmonary exercise test, were deemed eligible. Backward and forward citation tracking on eligible records were used to complement the results of database searching. Risk of bias at the study level was assessed using QUADOMICS. RESULTS: Twenty-two studies were included and 667 metabolites, measured in plasma (n = 619), serum (n = 18), skeletal muscle (n = 16), urine (n = 11), or sweat (n = 3), were identified. Lipids were the metabolites most commonly positively (n = 174) and negatively (n = 274) associated with CRF. Specific circulating glycerophospholipids (n = 85) and cholesterol esters (n = 17) were positively associated with CRF, while circulating glycerolipids (n = 152), glycerophospholipids (n = 42), acylcarnitines (n = 14), and ceramides (n = 12) were negatively associated with CRF. Interestingly, muscle acylcarnitines were positively correlated with CRF (n = 15). CONCLUSIONS: Cardiorespiratory fitness was associated with circulating and muscle lipidome composition. Causality of the revealed associations at the molecular species level remains to be investigated further. Finally, included studies were heterogeneous in terms of participants' characteristics and analytical and statistical approaches. PROSPERO REGISTRATION NUMBER: CRD42020214375.

Investigating the circulating sphingolipidome response to a single high-intensity interval training session within healthy females and males in their twenties (SphingoHIIT): Protocol for a randomised controlled trial.

Introduction: Growing scientific evidence indicates that sphingolipids predict cardiometabolic risk, independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, it remains largely unknown if and how exercise, a simple, low-cost, and patient-empowering modality to optimise cardiometabolic health, influences sphingolipid levels. The SphingoHIIT study aims to assess the response of circulating sphingolipid species to a single session of high-intensity interval training (HIIT). Methods: This single-centre randomised controlled trial (RCT) will last 11 days per participant and aim to include 32 young and healthy individuals aged 20-29 (50% females). Participants will be randomly allocated to the HIIT (n= 16) or control groups (physical rest, n= 16). Participants will self-sample fasted dried blood spots for three consecutive days before the intervention (HIIT versus rest) to determine baseline sphingolipid levels. Dried blood spots will also be collected at five time points (2, 15, 30, 60min, and 24h) following the intervention (HIIT versus rest). To minimise the dietary influence, participants will receive a standardised diet for four days, starting 24 hours before the first dried blood sampling. For females, interventions will be timed to fall within the early follicular phase to minimise the menstrual cycle's influence on sphingolipid levels. Finally, physical activity will be monitored for the whole study duration using a wrist accelerometer. Ethics and dissemination: The Ethics Committee of Northwest and Central Switzerland approved this protocol (ID 2022-00513). Findings will be disseminated in scientific journals and meetings. Trial Registration The trial was registered on www.clinicaltrials.gov (NCT05390866, https://clinicaltrials.gov/ct2/show/NCT05390866) on May 25, 2022.