Retinal endothelial function, physical fitness and cardiovascular risk: a diagnostic challenge

Introduction: Dynamic retinal vessel analysis (DVA) is a new non-invasive method to quantify microvascular endothelial dysfunction by flicker light-induced dilatation (FID). FID has been shown to be impaired in type 2 diabetes as well as heart failure. The aim of the study was to analyze FID in healthy active versus healthy sedentary and cardiovascular (CV) risk patients in addition to corresponding static vessel diameters. Methods: Thirty-one healthy active (HA, mean age 60 +/- 8 years), 33 healthy sedentary individuals (HS, 59 +/- 7 years) and 76 sedentary patients with increased CV risk (SR, 58 +/- 6 years) were included in this cross-sectional study. Group differences in CV risk factors and cardiorespiratory fitness, maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the arteriolar (AFarea) and venular (VFarea) area under the flicker curve were analyzed. The central retinal arteriolar and venular diameters were used to calculate the arteriolar-to-venular diameter ratio (AVR). Results: HS [ADmax = 3.5 (2.1)%; AFarea = 48.2 (31.9)%*s] showed higher FID compared to SR [ADmax = 2.7 (1.8)%, p = 0.021; AFarea = 34.5 (26.5)%*s, p = 0.006] and HA [AFarea = 32.8 (23.1)%*s, p = 0.029]. HA and SR did not significantly differ. HA had a higher AVR (0.87 +/- 0.05) compared to HS (0.83 +/- 0.04, p < 0.001) with further deterioration in SR (0.79 +/- 0.05, p < 0.001). Interestingly, 28 participants had impaired FID but normal AVR and 43 participants had normal FID but impaired AVR. Discussion: FID can differentiate between sedentary low and high risk individuals. However, FID in healthy active persons (HA) seemed impaired with a concomitant higher AVR. We postulate that lower FID in HA may be explained by predilatated arterioles and a reduced dilatation reserve. We recommend combination of FID with analysis of retinal vessel diameters to differentiate functional non-responders from manifest microvascular endothelial dysfunction and, thereby, improve microvascular risk stratification in a personalized medicine approach. Clinical Trial Registration: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show /NCT02796976)

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.peerReviewe

The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial

Study Objectives Insomnia increases the risk of negative disease trajectory, relapse, and suicide in patients with depression. We aimed at investigating the effects of a single bout of aerobic exercise, performed after 02:00 pm, on the subsequent night’s sleep in patients with depression. Methods The study was designed as a two-arm parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, and adverse events. Results Ninety-two patients were randomized to the exercise (N = 46) or control group (N = 46). There were no clinically relevant differences at baseline. Intent-to-treat analysis ANCOVA of follow-up sleep efficiency, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = −0.93, p = 0.59). There was no evidence for significant differences between both groups in any other objective or subjective sleep outcomes, daytime sleepiness, or adverse events. The intervention had an immediate positive effect on mood states, including depressiveness (β = −0.40, p = 0.003). Conclusions This is the first trial to study the effects of a single bout of aerobic exercise on sleep in patients with depression to the best of our knowledge. Aerobic exercise had no effect on sleep efficiency but had a strong beneficial effect on mood and did not increase adverse outcomes. These results add to the growing body of evidence that, contrary to sleep hygiene recommendations, exercise after 02:00 pm is not detrimental for sleep. Clinical Trial Registration Clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03673397. Protocol registered on September 17, 2018

In Athletes, the Diurnal Variations in Maximum Oxygen Uptake Are More Than Twice as Large as the Day-to-Day Variations

In competitive sports any substantial individual differences in diurnal variations in maximal performance are highly relevant. Previous studies have exclusively focused on how the time of day affects performance and disregarded the maximal individual diurnal variation of performance. Thus, the aims of this study were (1) to investigate the maximum diurnal variation in maximum oxygen uptake (VO2max), (2) to compare the diurnal variation of VO2max during the day to the day-to-day variation in VO2max, and (3) to investigate if there is a time-of-day effect on VO2max. Ten male and seven female athletes (mean VO2max: 58.2 ± 6.9 ml/kg/min) performed six maximal cardiopulmonary exercise tests including a verification-phase at six different times of the day (i.e., diurnal variation) and a seventh test at the same time the sixth test took place (i.e., day-to-day variation). The test times were 7:00, 10:00, 13:00, 16:00, 19:00, and 21:00. The order of exercise tests was the same for all participants to ensure sufficient recovery but the time of day of the first exercise test was randomized. We used paired t-tests to compare the nadir and peak of diurnal variations, day-to-day variations and the difference between diurnal and day-to-day variations. The mean difference in VO2max was 5.0 ± 1.9 ml/kg/min (95% CI: 4.1, 6.0) for the diurnal variation and 2.0 ± 1.0 ml/kg/min (95% CI: 1.5, 2.5) for the day-to-day variation. The diurnal variation was significantly higher than the day-to-day variation with a mean difference of 3.0 ± 2.1 ml/kg/min (95% CI: 1.9, 4.1). The linear mixed effects model revealed no significant differences in VO2max for any pairwise comparison between the different times of the day (all p &gt; 0.11). This absence of a time-of-day effect is explained by the fact that peak VO2max was achieved at different times of the day by different athletes. The diurnal variations have meaningful implications for competitive sports and need to be considered by athletes. However, the results are also relevant to research. To increase signal-to-noise-ratio in intervention studies it is necessary to conduct cardiopulmonary exercise testing at the same time of the day for pre- and post-intervention exercise tests

Normative data and standard operating procedures for static and dynamic retinal vessel analysis as biomarker for cardiovascular risk

Retinal vessel phenotype is predictive for cardiovascular outcome. This cross-sectional population-based study aimed to quantify normative data and standard operating procedures for static and dynamic retinal vessel analysis. We analysed central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents, as well as retinal endothelial function, measured by flicker light‐induced maximal arteriolar (aFID) and venular (vFID) dilatation. Measurements were performed in 277 healthy individuals aged 20 to 82 years of the COmPLETE study. The mean range from the youngest compared to the oldest decade was 196 ± 13 to 166 ± 17 µm for CRAE, 220 ± 15 to 199 ± 16 µm for CRVE, 3.74 ± 2.17 to 3.79 ± 2.43% for aFID and 4.64 ± 1.85 to 3.86 ± 1.56% for vFID. Lower CRAE [estimate (95% CI): - 0.52 (- 0.61 to - 0.43)], CRVE [- 0.33 (- 0.43 to - 0.24)] and vFID [- 0.01 (- 0.26 to - 0.00)], but not aFID, were significantly associated with older age. Interestingly, higher blood pressure was associated with narrower CRAE [- 0.82 (- 1.00 to - 0.63)] but higher aFID [0.05 (0.03 to 0.07)]. Likewise, narrower CRAE were associated with a higher predicted aFID [- 0.02 (- 0.37 to - 0.01)]. We recommend use of defined standardized operating procedures and cardiovascular risk stratification based on normative data to allow for clinical implementation of retinal vessel analysis in a personalized medicine approach

Should sports and exercise medicine be taught in the Swiss undergraduate medical curricula? A survey among 1764 Swiss medical students

Objectives The global lack of sports and exercise medicine (SEM) teaching at medical schools contrasts with evidence that physical activity (PA) plays a major role in preventing and treating non-communicable diseases (NCDs). The aims of this study were to (a) examine whether Swiss medical students are expected to acquire SEM-related skills and knowledge, (b) systematically reviewed SEM teaching in the Swiss undergraduate medical curricula, (c) assess if Swiss medical students are aware of SEM and (d) whether they would like SEM to be included in their curricula. Methods Two authors independently screened the 'Principal Relevant Objectives and Framework for Integrative Learning and Education in Switzerland' (PROFILES) for SEM-related learning objectives and reviewed the curricula. 7708 Swiss medical students were invited to participate in an online survey. Results 32 SEM-related learning objectives were identified in PROFILES with 20 of them linked to PA. Four of eight Swiss medical schools display limited mandatory SEM teachings. 1764 students participated in the survey (482.0% of the necessary sample size, 22.9% of all Swiss medical students). One in two students knew that SEM includes preventing and treating NCDs. Almost 95% of the participants would like SEM to be included in the curricula. Conclusion Despite its inclusion in PROFILES and comprehensive evidence that SEM should be taught at medical schools, this is scarcely the case in Switzerland. Swiss medical students have limited understanding of SEM, but are keen to have it included in the curricula. This study highlights the need for more comprehensive SEM teaching at Swiss medical schools

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

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 (β [95% CI] −0.09 [−0.11 to −0.06] kg/m2, p &lt; 0.001), a lower systolic BP (β [95% CI] −0.09 [−0.15 to −0.03] mmHg, p = 0.004) and a higher AVR (β [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)

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

A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents