RELATION OF PULSE WAVE VELOCITY TO CONTEMPORANEOUS AND HISTORICAL BLOOD PRESSURE IN FEMALE TWINS:Arterial Stiffness and Blood Pressure

An association between blood pressure and aortic stiffness is well known, but ambiguity remains as to whether one precedes the other. This study aimed to investigate the association of aortic stiffness with contemporaneous versus historic blood pressure and direction of causality between aortic stiffening and hypertension in female twins. METHODS: Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), and mean arterial pressure (MAP) was recorded in 2037 female TwinsUK participants (mean age: 62.4±9.7 years) at a single time point. A subset of 947 participants had repeat PWV and MAP measures (mean interval 5.5±1.7 years) with additional historic MAP (mean interval 6.6±3.3 years before baseline). RESULTS: Cross-sectional multivariable linear regression analysis confirmed PWV significantly associated with age and MAP. In longitudinal analysis, annual progression of PWV was not associated with historic MAP (standardized beta coefficient [β]=-0.02, P=0.698), weakly associated with baseline MAP (β=0.09, P=0.049) but strongly associated with progression (from baseline to most recent measurement) of MAP (β= 0.26, P<0.001). Progression of MAP associated with both baseline and progression of PWV (β=0.13, P=0.003 and β=0.24, P<0.001, respectively). CONCLUSIONS: Progression of aortic stiffness associates more strongly with contemporaneous MAP compared with historic MAP. In contrast, progression of MAP is associated with prior arterial stiffness. These findings suggest a bidirectional relationship between arterial stiffness and blood pressure, and that lowering blood pressure may prevent a cycle of arterial stiffening and hypertension

Gut microbial diversity is associated with lower arterial stiffness in women

© The Author(s)2018 All rights reserved. Aims The gut microbiome influences metabolic syndrome (MetS) and inflammation and is therapeutically modifiable. Arterial stiffness is poorly correlated with most traditional risk factors. Our aim was to examine whether gut microbial composition is associated with arterial stiffness.Methods We assessed the correlation between carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, and and results gut microbiome composition in 617 middle-aged women from the TwinsUK cohort with concurrent serum metabolomics data. Pulse wave velocity was negatively correlated with gut microbiome alpha diversity (Shannon index, Beta(SE)= -0.25(0.07), P = 1 10 -4 ) after adjustment for covariates. We identified seven operational taxonomic units associated with PWV after adjusting for covariates and multiple testing—two belonging to the Ruminococcaceae family. Associations between microbe abundances, microbe diversity, and PWV remained significant after adjustment for levels of gut-derived metabolites (indolepropionate, trimethylamine oxide, and phenylacetylglutamine). We linearly combined the PWV-associated gut microbiome-derived variables and found that microbiome factors explained 8.3% (95% confidence interval 4.3–12.4%) of the variance in PWV. A formal mediation analysis revealed that only a small proportion (5.51%) of the total effect of the gut microbiome on PWV was mediated by insulin resistance and visceral fat, c-reactive protein, and cardiovascular risk factors after adjusting for age, body mass index, and mean arterial pressure. Conclusions Gut microbiome diversity is inversely associated with arterial stiffness in women. The effect of gut microbiome composition on PWV is only minimally mediated by MetS. This first human observation linking the gut microbiome to arterial stiffness suggests that targeting the microbiome may be a way to treat arterial ageing

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity

Measurement of pulse wave velocity in children:comparison of volumetric and tonometric sensors, brachial-femoral and carotid-femoral pathways

BACKGROUND: Pulse wave velocity (PWV), a measure of arterial stiffness strongly predictive of cardiovascular risk in adults, is usually measured by sequential ECG-referenced carotid and femoral tonometry. A simplified technique, more suitable for use in children, employs simultaneous volumetric recording from a sensor applied over the carotid artery and a cuff applied over the femoral artery or arm and thigh pressure cuffs applied over the brachial and femoral arteries. The purpose of this study was to compare PWV computed over the carotid-femoral path (PWVcf) with that over the brachial-femoral path (PWVbf) using a volumetric system (Vicorder) and to compare values of PWVcf obtained by the volumetric and a tonometric method (SphygmoCor) in children. METHOD: Vicorder PWVcf and PWVbf were compared in 156 children (3–18 years, 110 with chronic kidney disease), and PWVcf by Vicorder was compared to PWVcf by SphygmoCor in a subset of 122 patients. RESULTS: PWVcf by Vicorder was moderately correlated with PWVcf by SphygmoCor (R = 0.50, P < 0.000). PWVbf and PWVcf Vicorder were more closely correlated (R = 0.75, P < 0.0001), but with a significant systematic difference. Applying a correction factor to PWVbf measurements gave results similar to those obtained over the carotid-femoral path. Within-patient coefficients of variation for repeated measures were 5.9, 7.8, and 8.5% for PWVbf (Vicorder), PWVcf (Vicorder) and PWVcf (SphygmoCor), respectively. All PWV values showed a similar relation to age. CONCLUSION: Volumetric methods appear reproducible and are easy to use in children, but values obtained by Vicorder and SphygmoCor are not interchangeable even when measured over the same pathway

Reproducibility of sequential ambulatory blood pressure and pulse wave velocity measurements in normotensive and hypertensive individuals

Errors in blood pressure (BP) measurement account for a large proportion of misclassified hypertension diagnoses. Ambulatory blood pressure monitoring (ABPM) is often considered to be the gold standard for measurement of BP, but uncertainty remains regarding the degree of measurement error. The aim of this study was to determine reproducibility of sequential ABPM in a population of normotensive and well controlled hypertensive individuals. METHODS: Individual participant data from three randomized controlled trials, which had recorded ABPM and carotid-femoral pulse wave velocity (PWV) at least twice were combined (n = 501). We calculated within-individual variability of daytime and night-time BP and compared the variability between normotensive (n = 324) and hypertensive (n = 177) individuals. As a secondary analysis, variability of PWV measurements was also calculated, and multivariable linear regression was used to assess characteristics associated with blood pressure variability (BPV). RESULTS: Within-individual coefficient of variation (CoV) for systolic BP was 5.4% (day) and 7.0% (night). Equivalent values for diastolic BP were 6.1% and 8.4%, respectively. No statistically significant difference in CoV was demonstrated between measurements for normotensive and hypertensive individuals. Within-individual CoV for PWV exceeded that of BP measurements (10.7%). BPV was associated with mean pressures, and BMI for night-time measurements. PWV was not independently associated with BPV. CONCLUSION: The variability of single ABPM measurements will still yield considerable uncertainty regarding true average pressures, potentially resulting in misclassification of hypertensive status and incorrect treatment regimes. Repeated ABPM may be necessary to refine antihypertensive therapy

Decreased arterial elasticity in children with nondialysis chronic kidney disease is related to blood pressure and not to glomerular filtration rate

We compared large artery mechanical properties in children with nondialysis stages of chronic kidney disease with those in children with normal renal function, examining the potential effect of blood pressure (BP) components and level of renal dysfunction. Common carotid artery mechanical properties, carotid-femoral pulse wave velocity, and carotid and peripheral BP were measured in children (n=226) with nondialysis chronic kidney disease (n=188; 11.9±3.7 years; 26%, 25%, 30%, 16%, and 3% in stages 1, 2, 3, 4 and 5, respectively) and healthy controls (n=38; 11.5±3.3 years). In children with nondialysis chronic kidney disease when compared with healthy controls, at similar levels of peripheral and carotid BP, carotid artery diastolic diameter and wall thickness were similar. In those with suboptimal BP (≥75th percentile), indices of arterial elasticity indicated greater stiffness than in healthy normotensive controls (distensibility: 92±31 versus 114±33 kPa −1 ×10 −3 , P =0.03; compliance: 2.1±0.7 versus 2.6±0.7 m 2 kPa −1 ×10 −6 , P =0.02; Young elastic modulus: 0.151±0.068 versus 0.109±0.049 kPa×10 3 , P =0.02; and wall stress: 83.6±23.5 versus 68.7±14.9 kPa, P =0.02). In all children, mechanical properties were independently related to carotid and peripheral BP components but not to estimated glomerular filtration rate. In children with nondialysis chronic kidney disease, changes in elastic properties of the carotid artery are primarily related to BP and not to glomerular renal function. </jats:p

Genetic aetiology of blood pressure relates to aortic stiffness with bi-directional causality:evidence from heritability, blood pressure polymorphisms, and Mendelian randomization

AIMS: Haemodynamic determinants of blood pressure (BP) include cardiac output (CO), systemic vascular resistance (SVR), and arterial stiffness. We investigated the heritability of these phenotypes, their association with BP-related single-nucleotide polymorphisms (SNPs), and the causal association between BP and arterial stiffness. METHODS AND RESULTS: We assessed BP, central BP components, and haemodynamic properties (during a single visit) including CO, SVR, and pulse wave velocity (PWV, measure of arterial stiffness) in 3531 (1934 monozygotic, 1586 dizygotic) female TwinsUK participants. Heritability was estimated using structural equation modelling. Association with 984 BP-associated SNP was examined using least absolute shrinkage and selection operator (LASSO) and generalized estimating equation regression. One and two-sample Mendelian randomization (MR) was used to estimate the causal direction between BP and arterial stiffness including data on 436 419 UK Biobank participants. We found high heritability for systolic and pulsatile components of BP (>50%) and PWV (65%) with overlapping genes accounting for >50% of their observed correlation. Environmental factors explained most of the variability of CO and SVR (>80%). Regression identified SNPs (n = 5) known to be associated with BP to also be associated with PWV. One-sample MR showed evidence of bi-directional causal association between BP and PWV in TwinsUK participants. Two-sample MR, confirmed a bi-directional causal effect of PWV on BP (inverse variance weighted (IVW) beta = 0.11, P < 0.02) and BP on arterial stiffness (IVW beta = 0.004, P < 0.0001). CONCLUSION: The genetic basis of BP is mediated not only by genes regulating BP but also by genes that influence arterial stiffness. Mendelian randomization indicates a bi-directional causal association between BP and arterial stiffness