Cardiac autonomic function, cardiovascular risk and physical activity in adolescents.

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The aims of this study were to investigate in adolescents: 1) the relationships of physical activity (PA) and cardiorespiratory fitness (CRF) to traditional CVD risk factors, rest and recovery autonomic function; and 2) whether autonomic function strengthens the associations between PA, CRF and CVD risk. Fifty-four (22 girls) adolescents had traditional CVD risk factors, rest and recovery autonomic function evaluated. CRF was measured using a steep ramp cycle test and PA was assessed with accelerometers. Resting HRV (and RMSSD30) and heart rate recovery (T30, HHRτ) were used. Clustered traditional (CVDRtrad) and autonomic (CVDRauto) risk scores were created and added to form a composite clustered CVD risk score (CVDRcom). PA and CRF were significantly and negatively associated with traditional CVD risk factors. Moderate (MPA) and vigorous (VPA) were positively related to resting RMSSD, and negatively related to T30 and HHRτ (all P<0.05). RMSSD30 recovered faster in the high compared to low median split for VPA. Stronger associations for CVDRcom compared to CVDRtrad were observed for MPA (CVDRcom: r2=0.32, P=<0.001; CVDRtrad: r2=0.17, P=0.002), and VPA (CVDRcom: r2=0.18, P=0.001; CVDRtrad: r2=0.06, P=0.08). These findings strengthen the proposed additional beneficial effects of PA on autonomic function above traditional CVD risk factors.RSO is funded by Science Without Borders, CAPES, Brazil, under the process number:10423-13-3

Reliability of autonomic and vascular components of baroreflex sensitivity in adolescents.

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Improvements in the autonomic and vascular systems are implicated in cardiovascular disease risk reduction. Baroreflex sensitivity (BRS) is composed of vascular and autonomic components. This study aimed to investigate between- and within-day reliability of BRS and its autonomic and vascular determinants in adolescents. Thirteen male adolescents (14·1 ± 0·5 y) participated in this study. For between-day reliability, participants completed four experimental visits separated by a minimum of 48-h. For within-day reliability, participants repeated BRS assessments three times in the morning with one hour between the measures. BRS was evaluated using the cross-spectral gain (LFgain) between blood pressure and heart rate interval. BRS was further divided into: 1) vascular component using arterial compliance (AC); and 2) autonomic component measured as LFgain divided by AC (LFgain/AC). LFgain, AC and LFgain/AC presented between-day coefficient of variation (CV) of 20%, 17%, and 20%, respectively. Similarly, variables associated with blood pressure control, such as cardiac output, mean arterial pressure, heart rate and total peripheral resistance, presented CVs ranging from 6% to 15%. Within-day reliability was poorer compared to between-day for LFgain (25%), AC (25%), and LFgain/AC (31%), as well as all hemodynamic variables (CVs from 11% to 22%, except heart rate with presented CV of 6%). This study indicates suitable between- and within-reliability of BRS and its autonomic and vascular determinants, as well as hemodynamic variables associated with BRS, in adolescents.This research was partially funded by Science Without Borders, CAPES, Brazil, under the process number:10423‐13‐3

Effects of exercise intensity on vascular and autonomic components of the baroreflex following glucose ingestion in adolescents.

This is the final version. Available from the publisher via the DOI in this record.PURPOSE: To investigate the effects of an oral glucose tolerance test (OGTT) on baroreflex sensitivity (BRS) in a sample of healthy adolescents, and how acute exercise bouts of different intensities alter the effects of the OGTT on BRS. METHODS: Thirteen male adolescents (14.0 ± 0.5 years) completed three conditions on separate days in a counterbalanced order: (1) high-intensity interval exercise (HIIE); (2) moderate-intensity interval exercise (MIIE); and (3) resting control (CON). At ~ 90 min following the conditions, participants performed an OGTT. Supine heart rate and blood pressure were monitored continuously at baseline, 60 min following the conditions, and 60 min following the OGTT. A cross-spectral method (LFgain) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic component. RESULTS: Although non-significant, LFgain moderately decreased post-OGTT when no exercise was performed (pre-OGTT = 24.4 ± 8.2 ms mmHg- 1; post-OGTT = 19.9 ± 5.6 ms mmHg- 1; ES = 0.64, P > 0.05). This was attributed to the decrease in LFgain/AC (pre-OGTT = 1.19 ± 0.5 ms µm- 1; post-OGTT = 0.92 ± 0.24 ms µm- 1; ES = 0.69, P > 0.05). Compared to CON (Δ = - 4.4 ± 8.7 ms mmHg- 1), there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 3.5 ± 8.2 ms mmHg- 1) and MIIE (Δ = 1.3 ± 9.9 ms mmHg- 1) had no effects on BRS following the OGTT (all ES < 0.5). Similarly, compared to CON (Δ = - 0.23 ± 0.40 ms µm- 1) there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 0.22 ± 0.49 ms µm- 1) and MIIE (Δ = 0.13 ± 0.36 ms µm- 1). CONCLUSION: A moderate non-significant decrease in BRS was observed in adolescents following a glucose challenge with no apparent effects of exercise.Science Without Border

The role of cardiopulmonary exercise testing (CPET) in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis (Protocol)

This is the final version. Available from BMC via the DOI in this record.Background Numerous studies have measured the prognostic associations between cardiorespiratory fitness and patient outcomes in congenital heart disease, but no systematic review has assessed these associations for all types of congenital heart disease. It is therefore a timely opportunity to syntheses all available data using a systematic review methodology. The aim of this study is to detail the protocol for a systematic review and meta-analysis. Objectives Within this paper we have developed a protocol for a prognostic factors systematic review and meta-analysis, to assess the role of cardiopulmonary exercise testing/cardiorespiratory fitness, in the prognosis of mortality and morbidity in congenital heart disease. Methods We have outlined, in detail, the process for this systematic review using the latest accepted methodological guidelines for prognostic factors research, such as the PICOTS system, CHARMS-PF data extraction, QUIPS risk of bias assessments and the prognostic GRADE guidelines (see list of abbreviations). Conclusion The implications of this review will aid future treatments, interventions and individual patient risk prediction. The publication of this protocol aims to improve scientific rigour by ensuring transparency in the systematic review and meta-analysis process.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Counci

Intrauterine environmental and genetic influences on the association between birthweight and cardiovascular risk factors: studies in twins as a means of testing the fetal origins hypothesis

Evidence has accumulated that low birthweight is associated with several risk factors for cardiovascular disease. However, it is not known whether or not these associations are due to a programmed response to intrauterine malnutrition or genetic factors influencing both birthweight and cardiovascular risk factors. Twin studies offer a unique opportunity to distinguish between intrauterine and genetic origins of the association between birthweight and cardiovascular risk. In our twin cohort, low birthweight was associated with insulin resistance, lower HDL and shorter height within both dizygotic and monozygotic twin pairs, suggesting that these associations are, at least in part, independent of genetic factors. In contrast, low birthweight was associated with blood pressure, total and LDL cholesterol, fibrinogen and sympathetic activation within dizygotic twin pairs, but not within monozygotic twin pairs. These differences between dizygotic and monozygotic twins suggest that these associations are, at least in part, due to genetic factors. Therefore, both intrauterine environmental and genetic factors appear to play a role in the association between birthweight and cardiovascular risk factors. In the future, strategies may be developed targeted at improving or preventing impaired intrauterine growth. However, the effects of interventions that comprise changes in environment within the normal range may be limited due to the possible important role of genetic factor

The utility of the reperfusion rate of tissue oxygen saturation as a measure of vascular endothelial function in adolescents: reliability, validity and sensitivity.

This is the final version. Available from Frontiers Media via the DOI in this record. Data availability statement: The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.Introduction: The near-infrared spectroscopy (NIRS)-derived reperfusion rate of tissue oxygen saturation (slope 2 StO2) may provide a surrogate measure of vascular function, however, this has yet to be examined in a paediatric population. This study investigated in adolescents: 1) the between-day reliability of NIRS-derived measurements; 2) the relationship between slope 2 StO2 and macro- (flow-mediated dilation, FMD) and microvascular (peak reactive hyperaemia, PRH) function; and 3) the effect of high-intensity interval exercise (HIIE) on slope 2 StO2, FMD, and PRH. Methods: Nineteen boys (13.3 ± 0.5 y) visited the laboratory on two occasions, separated by ∼ 1 week. On visit 1, participants underwent simultaneous assessment of brachial artery FMD and slope 2 StO2 and PRH on the internal face of the forearm. On visit 2, participants completed a bout of HIIE with slope 2 StO2, FMD and PRH measured pre-, immediately post- and 1.5 h post-exercise. Results: Slope 2 StO2 showed no mean bias (p = 0.18) and an intraclass correlation coefficient of 0.67 (p = 0.003) between visits. No significant correlation between slope 2 StO2 and FMD or PRH was observed on visit 1 (r = -0.04, p = 0.89 and r = -0.30, p = 0.23, respectively) or visit 2 pre-exercise (r = -0.28, p = 0.25 and r = -0.31, p = 0.20, respectively). Compared to pre-exercise, FMD decreased immediately post-exercise (p < 0.001) and then increased 1.5 h post-exercise (p < 0.001). No significant change was detected for slope 2 StO2 (p = 0.30) or PRH (p = 0.55) following HIIE. Conclusion: In adolescents, slope 2 StO2 can be measured reliably, however, it is not correlated with FMD or PRH and does not follow the acute time course of changes in FMD post-exercise. Hence, the use of slope 2 StO2 as a surrogate measure of vascular function in youth must be refuted

Effects of high-intensity interval training on the vascular and autonomic components of the baroreflex at rest in adolescents

This is the author accepted manuscript. The final version is available from Human Kinetics via the DOI in this recordPurpose: In a sample of healthy adolescents, we aimed to investigate the effects of high intensity interval exercise (HIIE) training and detraining on baroreflex sensitivity (BRS) and its vascular and autonomic components at rest Methods: Nineteen volunteers were randomly allocated to: 1) four weeks HIIE training performed three times per week; or 2) a control (CON) condition with no intervention for the same duration as HIIE training. PRE, POST and following two weeks of detraining (DET) resting supine heart rate and blood pressure were measured and a cross-spectral method (LFgain) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic determinant of BRS. Results: HIIE training was completed with 100% compliance. HIIE did not change resting LFgain (P=0.66; effect size (ES)=0.21), AC (P=0.44; ES=0.36) or LFgain/AC (P=0.68; ES=0.19) compared to CON. Conclusion: Four weeks of HIIE training does not change BRS and its autonomic and vascular determinant in a sample of healthy adolescents at rest

Late night salivary cortisol and cortisone should be the initial screening test for Cushing’s syndrome

Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late night salivary cortisol (LNSC) is recommended as a first line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy1. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low dose dexamethasone suppression test and 24-hour urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients).LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/l the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home.We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS

The role of cardiopulmonary exercise testing in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground: The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. Design: A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD. Methods: Electronic databases were systematically searched on the 30th of April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios (HR) across studies. Results: A total of 34 studies (18,335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled. Conclusion: Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well conducted prospective multicentre cohort studies are needed to confirm these findings.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Council (MRC

A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population

BACKGROUND: Reduced growth during infancy is associated with adult insulin resistance. In a UK Caucasian cohort, the CSH1.01 microsatellite polymorphism in the growth hormone-chorionic somatomammotropin hormone gene cluster was recently associated with increases in adult fasting insulin of approximately 23 pmol/l for TT homozygote males compared to D1D1 or D2D2 homozygotes (P = 0.001 and 0.009; n = 206 and 92, respectively), but not for females. TT males additionally had a 547-g lower weight at 1 year (n = 270; P = 0.008) than D2D2 males. We sought to replicate these data in healthy UK Caucasian subjects. We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers. RESULTS: We found no evidence for association of CSH1.01 genotype with adult male fasting insulin concentrations (TT/D1D1 P = 0.38; TT/D2D2 P = 0.18) or weight at 1 year in boys (TT/D1D1 P = 0.76; TT/D2D2 P = 0.85). For fasting insulin, our data can exclude the previously observed effect sizes as the 95 % confidence intervals for the differences observed in our study exclude increases in fasting insulin of 9.0 and 12.6 pmol/l for TT relative to D1D1 and D2D2 homozygotes, respectively. Whilst we have fewer data on boys' 1-year weight than the original study, our data can exclude a reduction in 1-year weight greater than 557 g for TT relative to D2D2 homozygotes. CONCLUSION: We have not found association of the CSH1.01 genotype with fasting insulin or weight at 1 year. We conclude that the original study is likely to have over-estimated the effect size for fasting insulin, or that the difference in results reflects the younger age of subjects in this study relative to those in the previous study