We performed untargeted profiling of circulating microRNAs (miRNAs) in a well characterized cohort of older adults to verify associations of health and disease-related biomarkers with systemic miRNA ...expression. Differential expression analysis revealed 30 miRNAs that significantly differed between healthy active, healthy sedentary and sedentary cardiovascular risk patients. Increased expression of miRNAs miR-193b-5p, miR-122-5p, miR-885-3p, miR-193a-5p, miR-34a-5p, miR-505-3p, miR-194-5p, miR-27b-3p, miR-885-5p, miR-23b-5b, miR-365a-3p, miR-365b-3p, miR-22-5p was associated with a higher metabolic risk profile, unfavourable macro- and microvascular health, lower physical activity (PA) as well as cardiorespiratory fitness (CRF) levels. Increased expression of miR-342-3p, miR-1-3p, miR-92b-5p, miR-454-3p, miR-190a-5p and miR-375-3p was associated with a lower metabolic risk profile, favourable macro- and microvascular health as well as higher PA and CRF. Of note, the first two principal components explained as much as 20% and 11% of the data variance. miRNAs and their potential target genes appear to mediate disease- and health-related physiological and pathophysiological adaptations that need to be validated and supported by further downstream analysis in future studies.Clinical Trial Registration: ClinicalTrials.gov: NCT02796976 ( https://clinicaltrials.gov/ct2/show/NCT02796976 ).
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.
Arterial stiffness (AST) is a main determinant of cardiovascular (CV) mortality. Long-term physical activity (PA) is considered to decrease age-related progression of AST but effects of short-term ...exercise interventions on AST remain unclear.
In a combined cross-sectional and interventional study approach, we investigated the effects of long-term PA and short-term high-intensity interval training (HIIT) on AST in an older population. 147 older individuals (mean age 59 ± 7 years) were assigned to three groups according to their PA and CV risk profile and compared: healthy active (HA,
= 35), healthy sedentary (HS,
= 33) and sedentary at risk (SR,
= 79). In addition, SR were randomized to either 12 weeks of HIIT or standard recommendations. Pulse wave velocity (PWV) was measured by applanation tonometry. Cardiorespiratory fitness (CRF) was performed by symptom-limited spiroergometry to determine maximal oxygen uptake (VO2max).
Higher CRF was associated with lower PWV (
< 0.001) and VO2max explained 18% of PWV variance. PWV was higher in SR (8.2 ± 1.4 m/s) compared to HS (7.5 ± 1.6 m/s) and HA (7.0 ± 1.1 m/s;
< 0.001). 12 weeks of HIIT did not change PWV in SR. HIIT-induced reduction in systolic BP was associated with a reduction in PWV (
< 0.05).
SR show higher PWV compared to HS and long-term PA is associated with lower PWV. Reduction of AST following short-term HIIT seems to depend on a concomitant decrease in blood pressure. Our study puts into perspective the effects of long- and short-term exercise on arterial wall integrity as treatment options for CV prevention in an older population.
ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).
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.
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).
HS ADmax = 3.5 (2.1)%; AFarea = 48.2 (31.9)%
s showed higher FID compared to SR ADmax = 2.7 (1.8)%,
= 0.021; AFarea = 34.5 (26.5)%
s,
= 0.006 and HA AFarea = 32.8 (23.1)%
s,
= 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,
< 0.001) with further deterioration in SR (0.79 ± 0.05,
< 0.001). Interestingly, 28 participants had impaired FID but normal AVR and 43 participants had normal FID but impaired AVR.
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.
ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ ct2/show/NCT02796976).
Age is a key determinant for the development of cardiovascular disease and higher age coincides with an increased prevalence of obesity and physical inactivity. The study examines the influence of ...physical activity on aging processes of physiological systems focusing on the mechanisms of vascular aging.
The study consists of two parts. The cross-sectional approach aims at examining the association of physical fitness and cardiovascular risk with large and small artery function in healthy older active (HOA,
= 40) and sedentary (HOS,
= 40) persons as well as older sedentary individuals with increased cardiovascular risk (OSR,
= 80) aged 50-80 years. In the interventional approach, the OSR group is randomized into a 12-week walking-based high intensity interval training (HIIT) group or a control condition, aiming at examining the effects of HIIT on arterial function in diseased older adults. Active lifestyle is defined as >9 metabolic equivalent of task (MET) per week and sedentary as ≤3 MET/week. Inclusion criteria for OSR are overweight or obesity (body mass index ≥30 kg/m
) plus at least one additional cardiovascular risk factor. The primary outcome is arterial stiffness as determined by aortic pulse wave velocity (PWV). The secondary outcomes are retinal arterial and venous diameters. Further cardiovascular assessments include peripheral PWV, central haemodynamics, retinal endothelial function, carotid intima media thickness, cardiac strain and diastolic function as well as autonomic function and inflammation. Physical fitness is measured by a treadmill-based spiroergometry to determine peak oxygen uptake.
The aim of the study is to demonstrate the importance of and need for specific physical activity programs for seniors to achieve healthier aging as a long-term goal. Vascular function defines disease- and age-related end organ damage and represents the potential to contain health at older age. This research will identify cardiovascular biomarkers that best resemble underlying cardiovascular risk in age and disease. The integrated approach will help define new recommendations for treatment guidance of exercise therapy in an aging population. ClinicalTrials. gov: NCT02796976; registered 02 June 2016 (retrospectively registered).
Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and ...leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrated strong beneficial effects of repetitive activities, such as active commuting or leisure‐time PA–related walking on AS in men, but not in women. Lower AS associated with endurance training was also found among men and premenopausal women. In contrast, intense occupational PA was related to stiffer vessels in men ( P <0.0001) and women ( P =0.0021) in a fully adjusted model. Combination of both, performing endurance training and having stiffness index values below median, resulted in the best survival. In contrast, subjects with elevated stiffness index at baseline without any endurance activities demonstrated the worst survival. Conclusions In this population representative sample, a differential impact of domains of self‐reported PA on AS was demonstrated. Our data strengthen the importance of regular endurance PA to induce a reduction of AS, which, in turn, may improve cardiovascular prognosis. We also report deleterious effects of intense occupational PA on stiffness index, a finding that needs further confirmation by larger prospective trials.
Objective:
Central hemodynamics are related to cardiovascular (CV) outcomes in adults, but associations with childhood CV risk remain unclear. The study aimed to investigate the association of ...obesity, physical activity, and fitness with parameters of central pulse wave reflection in young prepubertal children.
Methods:
In this cross-sectional study, 1,324 primary school children (aged 7.2 ± 0.4 years) were screened for parameters of pulse wave reflection such as augmentation index (AIx), central pulse pressure (CPP), body mass index (BMI), and cardiorespiratory fitness (CRF) by standardized procedures for children.
Results:
The mean AIx and AIx@75 were 22.2 ± 7.7 and 29.2 ± 9.2%, respectively. With each unit increase in BMI, AIx −0.226 (−0.328; −0.125)% and AIx@75 −0.444(−0.660; −0.229)% decreased, whereas peak forward pulse wave increased (
p
< 0.001). Increasing BMI was associated with higher CPP, but did not remain significant after adjustment for CRF and heart rate. One unit increase in CRF was associated with lower AIx@75 −0.509(−0.844; −0.173)%,
p
= 0.003 and lower reflection magnitude RM: −0.559 (−0.890; −0.227),
p
= 0.001, independent of body weight and height. Girls had significantly higher AIx, AIx@75, peak backward pulse wave, and RM compared with boys.
Conclusion:
Childhood obesity was associated with higher CPP but lower augmentation of the reflected pulse wave in children. Assessment of central blood pressures appears to be a valuable asset to childhood CV risk screening. The validity of augmentation indices during childhood development and the association with early vascular aging in children need to be verified in long-term follow-up studies. Physical activity and fitness have the potential to improve vascular hemodynamics in susceptible children and, thus, counteract vascular aging.
Trial registry: ClinicalTrials.gov:
Exercise and Arterial Modulation in Youth.
Identifier:
NCT02853747; URL:
https://clinicaltrials.gov/ct2/show/NCT02853747
.
Socioeconomic barriers and lifestyle conditions affect development of cardiovascular disease in adults, but little is known about the association of parental lifestyle and education with childhood ...health. We aimed to investigate the association of socioeconomic status (SES), migration background, parental physical activity (PA) and smoking status with micro-and macrovascular health in children.
In 2016/2017, 833 school children (aged 7.2 ± 0.4 years) in Basel (Switzerland) were screened for retinal arteriolar-to-venular ratio (AVR), pulse wave velocity (PWV), SES, migration background and parental PA as well as smoking status.
High parental PA levels were associated with a favorable higher AVR (
= 0.020) and lower PWV (
= 0.035), but not independent of parental smoking status. Children with parents who smoked had a higher PWV 4.39 (4.35-4.42) m/s compared to children with non-smoking parents 4.32 (4.29-4.34) m/s,
= 0.001. Children of parents with a low household income had a higher PWV 4.36 (4.32-4.41) m/s compared to children of parents with a high household income 4.30 (4.26-4.34) m/s,
= 0.033. Low parental educational level was associated with a lower AVR 0.86 (0.85-0.88) compared to children with highly educated parents AVR:0.88 (0.87-0.88),
= 0.007; PWV: 4.33 (4.30-4.35) m/s,
= 0.041. Children with a European background showed a higher AVR 0.88 (0.87-0.88) compared to non-European children AVR: (0.86 (0.85-0.87),
= 0.034.
Parental PA is associated with better macro- and microvascular childhood health. However, the positive association is lost when parental smoking is considered in the analysis. Socioeconomic factors seem to associate with subclinical vascular alterations in children. Primary prevention programs should focus on including parental lifestyle interventions and educational programs to reduce the burden of lifestyle-associated barriers in order to improve cardiovascular health during lifespan.
ClinicalTrials.gov Exercise and Arterial Modulation in Youth, https://clinicaltrials.gov/ct2/show/NCT02853747, NCT02853747.
Low-grade systemic inflammation is responsible for atherosclerotic lesions in patients with rheumatic diseases. Vascular dysfunction is a precursor of atherosclerosis and can be improved by physical ...activity (PA). Our aim was to asses micro- and macrovascular function as well as PA and cardiorespiratory fitness (CRF) in patients with rheumatic diseases in the absence of cardiovascular (CV) comorbidities compared to controls.
Fifty-one patients without CV comorbidities were compared to 35 controls. Retinal microvascular diameters were assessed using a Retinal Vessel Analyzer. Arterial stiffness (AST) was measured by applanation tonometry. CRF was assessed as peak oxygen consumption and PA was assessed with a questionnaire.
Retinal venular diameters were significantly wider in patients median 221 μm (interquartile range (IQR) 211, 231) compared to controls median 215 μm (IQR 196, 223);
= 0.01. One hour increase of PA per week led to a venular constriction of -0.56 μm (95%CI -1.09, -0.03;
= 0.04). In our patients with low disease activity (median DAS28 1.9; median BASDAI 2.8), no differences in AST were evident compared to controls. The association of PA and CRF with AST was not independent of blood pressure.
Patients with rheumatic disease and mild-to-moderate disease activity show an impairment of the retinal microvasculature but not of large artery stiffness. Retinal vessel analysis seems to be a sensitive biomarker to unmask vascular impairments even in the absence of classic CV risk factors. PA may have the potential to counteract the development of small artery disease at early stages of rheumatic disease.
Treatment of hypertension and its complications remains a major ongoing health care challenge. Around 25% of heart attacks in Europe are already attributed to hypertension and by 2025 up to 60% of ...the population will have hypertension. Physical inactivity has contributed to the rising prevalence of hypertension, but patients who exercise or engage in physical activity reduce their risk of stroke, myocardial infarction, and cardiovascular mortality. Hence, current international guidelines on cardiovascular disease prevention provide generic advice to increase aerobic activity, but physiological responses differ with blood pressure (BP) level, and greater reductions in BP across a population may be achievable with more personalized advice. We performed a systematic review of meta-analyses to determine whether there was sufficient evidence for a scientific Consensus Document reporting how exercise prescription could be personalized for BP control. The document discusses the findings of 34 meta-analyses on BP-lowering effects of aerobic endurance training, dynamic resistance training as well as isometric resistance training in patients with hypertension, high-normal, and individuals with normal BP. As a main finding, there was sufficient evidence from the meta-review, based on the estimated range of exercise-induced BP reduction, the number of randomized controlled trials, and the quality score, to propose that type of exercise can be prescribed according to initial BP level, although considerable research gaps remain. Therefore, this evidence-based Consensus Document proposes further work to encourage and develop more frequent use of personalized exercise prescription to optimize lifestyle interventions for the prevention and treatment of hypertension.
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