Early Arterial Intimal Thickening and Plaque Is Related with Treatment Regime and Cardiovascular Disease Risk Factors in Young Adults Following Childhood Hematopoietic Stem Cell Transplantation

The long-term vascular effects following childhood hematopoietic stem cell transplantation (HSCT) are not well characterized. We compared arterial wall morphology and function using very-high resolution ultrasound (25–55 MHz) in 62 patients following autologous (n = 19) or allogenic (n = 43) HSCT for childhood malignancies and hematological disease (median age 25.9 years, IQR 21.1–30.1; median follow-up time 17.5 years IQR 14.1–23.0) with an age matched healthy control group (n = 44). Intima-media thickness of carotid (CIMT 0.49 ± 0.11 vs. 0.42 ± 0.06 mm, p 0.06 mm) of femoral or radial arteries (n = 17) and subclinical carotid or femoral plaques (n = 18) were more common (p 30 kg/m2, hsCRP >2.5 mg/L, hypertension, HbA1c > 42 mmol/L, and cumulative anthracycline >150 mg/m2. Cumulative metabolic syndrome criteria and cardiovascular disease (CVD) risk factors were more common among HSCT and related with CIMT (p < 0.001), but CIMT was similar among controls and HSCT without CVD risk factors. Long-term childhood HSCT survivors show early arterial aging related with radiation, metabolic, and CVD risk factors. Prevention of risk factors could potentially decelerate early arterial wall thickening

Childhood cardiovascular morphology and function following abnormal fetal growth

Studies examining the link between abnormal fetal growth and cardiac changes in childhood have presented conflicting results. We studied the effect of abnormal fetal growth on cardiac morphology and function during childhood, while controlling for body size, composition and postnatal factors. We report on the follow-up of 90 children (median age 5.81 years, IQR 5.67; 5.95) born appropriate for gestational age (AGA, N = 48), small for gestational age (SGA, N = 23), or large for gestational age (LGA, N = 19); SGA and LGA defined as birth weight Z-score + 2, respectively. We examined the heart using echocardiography, including Doppler and strain imaging, in relation to anthropometrics, body composition, blood pressure, physical activity, and diet. Although groupwise differences in body size decreased during the first year after birth, LGA remained larger at follow-up, with higher lean body mass and BMI, while SGA were smaller. Slight changes in left ventricular diastolic function were present in SGA and LGA, with SGA showing increased mitral diastolic E- and A-wave peak flow velocities, and increased septal E/E ' ratio, and LGA showing larger left atrial volume adjusted for sex and lean body mass. In univariate analyses, lean body mass at follow-up was the strongest predictor of cardiac morphology. We found no groupwise differences at follow-up for ventricular sphericity, cardiac morphology adjusted for lean body mass and sex, or blood pressure, diet, or physical activity. Cardiac morphology is predicted by lean body mass during childhood, even in the setting of abnormal fetal growth. Our results are consistent with a limited effect of fetal programming on cardiac dimensions during childhood. Minor changes in diastolic function are present in both SGA and LGA children, however, the clinical significance of these changes at this stage is likely small.Peer reviewe

Arterial health during early childhood following abnormal fetal growth

Background Abnormal fetal growth is associated with increased cardiovascular risk in adulthood. We investigated the effect of fetal programming on arterial health and morphology during early childhood. Methods We examined 90 children (median age 5.81 years, interquartile range: 5.67; 5.95), born small for gestational age with fetal growth restriction, large or appropriate for gestational age (SGA, N = 23, LGA, N = 19, AGA N = 48). We measured body composition, anthropometrics, blood pressure, pulse wave velocity (PWV), lipids, glucose and inflammatory markers, and assessed carotid, brachial, radial and femoral arterial morphology and stiffness using very-high resolution ultrasound (46-71 MHz). Results LGA showed increased anthropometry, lean body mass and body mass index. SGA displayed decreased anthropometry and lean body mass. Blood pressure, PWV, carotid artery stiffness and blood work did not differ groupwise. Differences in lumen diameters, intima-media thicknesses (IMT) and adventitia thicknesses disappeared when adjusted for lean body mass and sex. In multiple regression models arterial dimensions were mainly predicted by lean body mass, with birth weight remaining associated only with carotid and brachial lumen dimensions, and not with IMTs. Carotid-femoral PWV was predicted by height and blood pressure only. No independent effect of adiposity was observed. Conclusions Arterial dimensions in childhood associate with current anthropometrics, especially lean body mass, and sex, explaining differences in arterial layer thickness. We found no signs of fetal programming of cardiovascular risk or arterial health in early childhood.Peer reviewe

NON-INVASIVE VASCULAR VERY-HIGH RESOLUTION ULTRASOUND TO QUANTIFY ARTERY INTIMA LAYER THICKNESS : VALIDATION OF THE FOUR-LINE PATTERN

Preliminary findings suggest that very-high resolution ultrasound (VHRU, 55 MHz) could differentiate arterial intima layer thickness (IT) non-invasively in vivo. We aimed to validate ultrasound-derived IT measurements and describe a four-line pattern consistent with intimal thickening. VHRU was applied to temporal arteries of 37 patients with suspected giant cell arteritis without inflammation on histology. Anatomically matched ultrasound-derived measurements of arterial layer thickness with the leading-edge method was compared to histology. Intimal thickening (IT >0.06 mm on histology) was identified as a four-line pattern in VHRU with a sensitivity of 96.3% and a specificity of 100%. Histologic and VHRU IT measurement agreement was excellent (mean difference 0.007 mm; 95% limits of agreement, -0.043 to 0.057) and intra-class coefficient (ICC) 0.923 (95% confidence interval [CI], 0.833-0.964). Intra- and inter-observer agreements for VHRU IT were high: ICC 0.946 (95% CI, 0.877-0.976) and 0.872 (95% CI, 0.773-0.943). VHRU utilizing the leading-to-leading edge method allows accurate and reliable measurements of arterial IT in patients with IT >0.06 mm. Measurements of IT will provide the opportunity to explore early subclinical structural intimal changes in the arterial wall increasing with age. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.Peer reviewe

Ultra-high frequency ultrasound delineated changes in carotid and muscular artery intima-media and adventitia thickness in obese early middle-aged women

Obesity is linked to increased arterial size, carotid intima-media thickness and arterial stiffness. The effects of obesity and body composition on muscular artery intima-media and adventitia thickness has previously not been established. The aim of this study was to explore associations between carotid and muscular artery wall layer thickness with body composition and cardiovascular risk factors in early middle-aged women. This is a cross-sectional study including 199 women aged 40 +/- 4 years. Arterial lumen (LD), intima-media (IMT) and adventitia thickness (AT) were measured from carotid, brachial and radial arteries using ultra-high frequency ultrasound (22-71 MHz). Women with obesity had increased IMT in carotid (0.47 vs 0.45 mm), brachial (0.19 vs 0.17 mm) and radial arteries (0.16 vs 0.15 mm) and increased brachial AT (0.14 vs 0.13 mm). In multiple regression models all arterial LD (beta-range 0.02-0.03 mm/kg/m(2)), IMT (beta-range 0.91-3.37 mu m/kg/m(2)), AT (beta-range 0.73-1.38 mu m/kg/m(2)) were significantly associated with BMI. The IMT of all arteries were significantly associated with systolic blood pressure (beta-range 0.36-0.85 mu m/mmHg), attenuating the association between IMT and BMI (beta-range 0.18-2.24 mu m/kg/m(2)). Obese early middle-aged women have increased arterial intima media thickness and brachial artery adventitia thickness compared to non-obese counterparts. The association between BMI and intima-media thickness is partly mediated through blood pressure levels.Peer reviewe

Maternal obesity and gestational diabetes : Impact on arterial wall layer thickness and stiffness in early childhood - RADIEL study six-year follow-up

Background and aims: Gestational diabetes (GDM) and maternal obesity are linked to weight gain in childhood and an increased risk of cardiovascular disease later in life. We assessed the effects of GDM and maternal obesity on arterial function and morphology in relation to body anthropometrics and composition in early childhood. Methods: We assessed body size and composition, blood pressure (BP), arterial morphology and stiffness in 201 pairs of obese mothers (pre-pregnancy BMI 30.7 +/- 5.6 kg/m(2), 96 with GDM) and their children at 6.1 years (SD 0.5). Results: Child BMI (z-score 0.45 +/- 0.92; p <0.001) and common carotid intima-media thickness (IMT, z-score 0.15 +/- 0.75, p=0.003) were increased compared with a healthy Finnish reference population. No associations with maternal GDM was found. Carotid IMT and pulse wave velocity were unrelated to child sex, anthropometrics, body composition, BP, as well as maternal anthropometrics and body composition. Carotid stiffness was independently predicted by second trimester fasting glucose. Child lean body mass was the strongest independent predictor for radial (RA), and brachial artery (BA) lumen diameter (LD) and BA IMT (LD: RA: r(2)=0.068, p <0.001; BA: r(2)=0.108, p <0.001; IMT: BA: r(2)=0.161, p <0.001) and carotid LD (r(2)=0.066, p <0.001). Conclusions: Children of obese mothers have increased BMI, blood pressure and carotid IMT suggesting a transgenerational effect of maternal obesity and clustering of cardiovascular risk factors in the population. Arterial dimensions were mainly predicted by child LBM, and not associated with maternal or child adiposity, or GDM. There was a weak association with maternal gestational fasting glucose and increased carotid artery stiffness.Peer reviewe

No effect of gestational diabetes or pre-gestational obesity on 6-year offspring left ventricular function-RADIEL study follow-up

Aims We aimed to investigate associations between pre-pregnancy obesity, gestational diabetes (GDM), offspring body composition, and left ventricular diastolic and systolic function in early childhood. Methods This is an observational study, including 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL; 96 with GDM, 128 with pre-pregnancy obesity) with follow-up from gestation to 6-year postpartum. Follow-up included dyads anthropometrics, body composition, blood pressure, and child left ventricular function with comprehensive echocardiography (conventional and strain imaging). Results Offspring left ventricular diastolic and systolic function was not associated with gestational glucose concentrations, GDM, or pregravida obesity. Child body fat percentage correlated with maternal pre-pregnancy BMI in the setting of maternal obesity (r = 0.23,P = 0.009). After adjusting for child lean body mass, age, sex, systolic BP, resting HR, maternal lean body mass, pre-gestational BMI, and GDM status, child left atrial volume increased by 0.3 ml (95% CI 0.1, 0.5) for each 1% increase in child body fat percentage. Conclusions No evidence of foetal cardiac programming related to GDM or maternal pre-pregnancy obesity was observed in early childhood. Maternal pre-pregnancy obesity is associated with early weight gain. Child adiposity in early childhood is independently associated with increased left atrial volume, but its implications for long-term left ventricle diastolic function and cardiovascular health remain unknown.Peer reviewe

Comparison of argon and air as thermal insulating gases in drysuit dives during military Arctic diving equipment development tests

Introduction: It is vital to protect divers from the cold, particularly in Arctic conditions. The insulating gas layer within the drysuit is crucial for reducing heat loss. The technical diving community has long claimed the superiority of argon over air as an insulating gas. Although argon is widely used, previous studies have shown no significant differences between the two gases. Owing to its lower heat conductivity, argon should be a better thermal insulating gas than air. Methods: The study aimed to determine whether argon is beneficial for reducing heat loss in divers during development of military drysuit diving equipment in Arctic water temperatures. Four divers completed 14 dives, each lasting 45 minutes: seven dives used air insulation and seven used argon insulation. Rectal and eight skin temperatures were measured from which changes in calculated mean body temperature (MBT) were assessed. Results: There was a significant reduction in area weighted skin temperature over time (0-45 minute) on air dives (Delta T-skin = -4.16 degrees C, SE = 0.445, P <0.001). On argon dives the reduction was significantly smaller compared to air dives (difference between groups = 2.26 degrees C, SE = 0.358, P Conclusion: Compared to air, argon may be superior as a drysuit insulating gas in Arctic water temperatures for some divers. Argon used as insulating gas can make diving safer and may diminish the risks of fatal diving accidents and occupational hazard risks in professional diving.Peer reviewe

Ideal Cardiovascular Health and Vascular Phenotype Associations in Mothers with Obesity and Their Six-Year-Old Children

Background: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype. Methods: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 +/- 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity. Results: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 +/- 0.2 vs 1.2 +/- 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 +/- 0.04 vs 0.35 +/- 0.04 mm, P=0.06). Conclusion: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.Peer reviewe