Associations Between Sedentary Time, Physical Activity, and Cardiovascular Health in 6-Year-Old Children Born to Mothers With Increased Cardiometabolic Risk.

PURPOSE: To assess associations between sedentary time (ST), physical activity (PA), and cardiovascular health in early childhood. METHOD: Cross-sectional study including 160 children (age 6.1 y [SD 0.5], 86 boys, 93 maternal body mass index ≥ 30 kg/m2, and 73 gestational diabetes) assessed for pulse wave velocity, echocardiography, ultra-high frequency 48-70 MHz vascular ultrasound, and accelerometery. RESULTS: Boys had 385 (SD 53) minutes per day ST, 305 (SD 44) minutes per day light PA, and 81 (SD 22) minutes per day moderate to vigorous PA (MVPA). Girls had 415 (SD 50) minutes per day ST, 283 (SD 40) minutes per day light PA, and 66 (SD 19) minutes per day MVPA. In adjusted analyses, MVPA was inversely associated with resting heart rate (ß = -6.6; 95% confidence interval, -12.5 to -0.7) and positively associated with left ventricular mass (ß = 6.8; 1.4-12.3), radial intima-media thickness (ß = 11.4; 5.4-17.5), brachial intima-media thickness (ß = 8.0; 2.0-14.0), and femoral intima-media thickness (ß = 1.3; 0.2-2.3). MVPA was inversely associated with body fat percentage (ß = -3.4; -6.6 to -0.2), diastolic blood pressure (ß = -0.05; -0.8 to -0.1), and femoral (ß = -18.1; -32.4 to -0.8) and radial (ß = -13.4; -24.0 to -2.9) circumferential wall stress in boys only. ST and pulse wave velocity showed no significant associations. CONCLUSIONS: In young at-risk children, MVPA is associated with cardiovascular remodeling, partly in a sex-dependant way, likely representing physiological adaptation, but ST shows no association with cardiovascular health in early childhood.

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 and > + 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.

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.

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.

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.

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 < 0.001), brachial, femoral, radial arteries, and local carotid stiffness, but not adventitial thickness, were increased (p < 0.001). Diffuse intimal thickening (>0.06 mm) of femoral or radial arteries (n = 17) and subclinical carotid or femoral plaques (n = 18) were more common (p < 0.001). Radiation predicted plaques (p < 0.001) and local carotid stiffness (p < 0.001), but not intimal thickening. CIMT was predicted by age, BMI >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.

Diagnostic performance and utility of very high-resolution ultrasonography in diagnosing giant cell arteritis of the temporal artery.

OBJECTIVE: Very-high resolution US (VHRU; 55 MHz) provides improved resolution and could provide non-invasive diagnostic information in GCA of the temporal artery. The objective of this study was to assess the diagnostic utility of VHRU-derived intima thickness (VHRU-IT) in comparison to high-resolution US halo-to-Doppler ratio (HRU-HDR) in patients referred for temporal artery biopsy. METHODS: VHRU and HRU of the temporal artery were performed before a biopsy procedure in 78 prospectively recruited consecutive patients who had received glucocorticoid treatment for a median of 8 days (interquartile range 0-13 days) before imaging. Based on the final diagnosis and biopsy findings, the study population was divided into the following four groups: non GCA (n = 40); clinical GCA with no inflammation on biopsy (n = 15); clinical GCA with inflammation limited to adventitia (n = 9); and clinical GCA with transmural inflammation (TMI; n = 11). RESULTS: Both VHRU and HRU were useful for identifying subjects with TMI, with VHRU outperforming HRU (area under curve: VHRU-IT 0.99, 95% CI 0.97, 1.00; HRU-HDR 0.74, 95% CI 0.52, 0.96; P=0.026). The diagnostic utility for diagnosing clinical GCA (negative biopsy) or inflammation limited to the adventitia was poor for both VHRU and HRU-HDR. From 5 days after initiation of glucocorticoid treatment, VHRU-IT was increased in eight of nine patients, whereas HRU-HDR was positive in three of seven patients. Both methods showed excellent inter-observer agreement (Cohen's κ: VHRU-IT 0.873; HRU-HDR 0.811). CONCLUSION: In suspected GCA, VHRU allows non-invasive real-time imaging of TMI manifestations of the temporal artery wall. VHRU-derived intimal thickness measurement seems to be more sensitive than the halo sign and HRU-HDR in detecting TMI in patients with prolonged glucocorticoid treatment.

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.

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 ±â€¯5.6 kg/m2, 96 with GDM) and their children at 6.1 years (SD 0.5). RESULTS: Child BMI (z-score 0.45 ±â€¯0.92; p < 0.001) and common carotid intima-media thickness (IMT, z-score 0.15 ±â€¯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: r2 = 0.068, p < 0.001; BA: r2 = 0.108, p < 0.001; IMT: BA: r2 = 0.161, p < 0.001) and carotid LD (r2 = 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.

Neonatal Arterial Morphology Is Related to Body Size in Abnormal Human Fetal Growth.

BACKGROUND: Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size. METHODS AND RESULTS: We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35-55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (R( 2) range, 0.37-0.47 for LD; 0.09-0.35 for intima-media thickness; 0.21-0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models P<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (P<0.01), but not with arterial wall layers. CONCLUSIONS: These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex.

Feasibility and precision of transcutaneous very-high resolution ultrasound for quantification of arterial structures in human neonates - comparison with conventional high resolution vascular ultrasound imaging.

BACKGROUND: Non-invasive transcutaneous very-high resolution ultrasound (VHRU, 25-55 MHz) has recently been developed to quantify superficial vascular structures in humans. The performance of the method has yet not been evaluated in vivo in neonates. The aim of the study was to compare VHRU with conventional high-resolution ultrasound (HRU, 7-12 MHz), and to assess the feasibility and precision of VHRU in this population. METHODS: 150 images from central elastic (common carotid, CCA) and peripheral muscular (brachial, BA; femoral, FA) arteries were obtained in 25 neonates of different gestational ages (range 33 + 0 to 41 + 5 gestational weeks) and weights (range 1570-4950 g) with VHRU, and the use of HRU for comparison assessed in five. RESULTS: Images were captured from CCAs with 35 MHz, FAs using 35 and 55 MHz, and BAs using 55 MHz. 12 MHz was unable to assess FAs and BAs, and the CCA IMT was grossly overestimated compared with 35-55 MHz. IMTs of the smallest BAs and FAs were beyond the axial resolution of VHRU (<0.05 mm), thus immeasurable. For VHRU, the intra-, inter- and test-retest coefficients of variation (CV) were for LDs (range 1.44-2.62 mm, CVs between 1.6 and 4.8%), IMATs (range 0.141-0.161 mm, CVs between 8.8 and 19.9%), and IMTs (range 0.062-0.165 mm, CVs between 12.8 and 24.8%) for the different arteries. CONCLUSION: VHRU is feasible, accurate and precise in the assessment of superficial proximal conduit arteries but unable to assess the abdominal aorta in human neonates HRU-derived neonatal conduit arterial wall layer thicknesses are below the ultrasound axial resolution.