Adrenal Steroid Metabolism and Blood Pressure in 5- to 7-Year-Old Children Born Preterm as Compared to Peers Born at Term

Background: Previous studies indicated preterm birth to be a risk factor for hypertension in adolescence and adulthood. However, studies in children investigating the underlying mechanisms are scarce.Objective: We hypothesized children born preterm to have higher excretion of cortisol and/or androgen metabolites per day concomitantly with higher blood pressure as compared to peers born at term. We thus aimed to compare urinary steroid profiles and blood pressure between 5- to 7-year-old children born preterm and peers born at term. Furthermore, aldosterone precursor excretion per day was compared between both groups.Methods: Blood pressure was measured in 236 children (preterms n = 116; gestational age 29.8 ± 2.6 (30; 24–33) weeks [mean ± standard deviation (median; range)]) using an automatic oscillometric device. Urinary steroid profiles were determined in 24-h urine samples (preterms n = 109; terms n = 113) using gas chromatographic-mass spectrometric analysis. To assess excretion of cortisol and androgen metabolites per day, major cortisol and androgen metabolites were summed, respectively. To assess aldosterone excretion per day tetrahydrocorticosterone, 5α-tetrahydrocorticosterone, and tetrahydro-11-deydrocorticosterone were summed.Results: Multiple regression analyses showed prematurity to be associated with systolic but not with diastolic blood pressure. When adjusted for potential confounders (prematurity, gender, age at day of examination, being born small for gestational age, breastfeeding, accelerated weight gain during infancy, family history of cardiovascular disease, parental hypertension, and body mass index) prematurity was shown to be associated with an increase in systolic blood pressure by 2.87 mmHg (95% confidence interval 0.48–5.27; p = 0.02). Cortisol, androgen metabolite, and aldosterone precursor excretion per day were not higher in individuals born preterm. In contrast to our hypothesis, multiple regression analysis showed prematurity to independently decrease cortisol and aldosterone precursor excretion per day (p < 0.001 and 0.04, respectively).Conclusion: This study provides further evidence for systolic blood pressure to be higher after preterm birth as early as at the age of 5 to 7 years. However, this seems not to be explained by elevated excretion of cortisol and/or androgen metabolites.

Abstract 51: Ambulatory Blood Pressure Phenotype And Cardiovascular Risk In Youth: The Ship-ahoy Study

We investigated whether blood pressure (BP) phenotype based on clinic & 24-hour ambulatory BP (ABP) was associated with intermediate markers of cardiovascular disease (CVD) in 374 adolescents enrolled in a study of the relationship of BP to CV risk. Clinic BP was measured by auscultation and categorized using the 2017 AAP guideline. ABP was measured for 24 hours by an oscillometric device and analyzed using the adult ABP wake SBP cut-point (130 mmHg). This created 4 BP phenotype groups: normal BP (n=224), white coat hypertensive (n=48), ambulatory hypertensive (n=57) & masked hypertensive (n=45). Echocardiographic parameters & carotid-femoral pulse wave velocity (PWVcf) were measured to assess CVD risk. Left ventricular mass (LVM) was lowest in the normal BP group, whereas multiple measures of cardiac function and PWVcf were worse in the masked and ambulatory hypertensive groups: Generalized linear models adjusted for body mass index (BMI) were constructed to examine the associations between BP phenotype and the measured CVD variables. ABP phenotype was an independent predictor of LVM, diastolic and systolic function and PWVcf in the unadjusted model. ABP phenotype remained significantly associated with diastolic function (E/e’, e’/a’), systolic function (ejection fraction) and increased arterial stiffness (PWVcf) after adjustment for BMI percentile (all p<=0.05). We conclude that BP phenotype is an independent predictor of markers of increased CVD risk in adolescents, including impaired cardiac function and increased vascular stiffness. ABP monitoring has an important role in CVD risk assessment in youth.

Abstract P117: Comparison Between Routine Clinical And Research Blood Pressure Measurements

Background: Prior studies have found a large difference between blood pressure (BP) when measured routinely in the clinic compared with research studies. We aimed to compare routine clinic BP to research-grade BP in a large, integrated health care system that has initiatives to standardize clinic BP measurements. Methods: We identified Kaiser Permanente Southern California members ≥ 65 years old diagnosed with hypertension and taking antihypertensive medication from the Ambulatory Blood Pressure in Older Adults (AMBROSIA) study. Research-grade BPs were obtained under standardized conditions by certified research staff using a semi-automatic oscillometric device, pre-programmed to take 3 measurements at 1-minute intervals. The average of the 3 BPs was used. The most recent (prior to study enrollment) routine clinic BP from an outpatient, non-urgent clinical care encounter, measured using a semi-automatic oscillometric device, was obtained via electronic health records. If there were multiple BP readings on the same day, the first reading was used. The mean difference between clinic BP and research-grade BP was tested using paired t-tests, while the Pearson correlation and a Bland-Altman analysis were used to assess level of agreement. Results: We included 309 participants (mean age 75 ± 6 years; 54% female; 49% non-Hispanic white, 17% non-Hispanic Black, 17% Hispanic, 15% Asian/Pacific Islander). When measured in routine clinic practice and in the research study, the mean (SD) systolic BP (SBP) was 135 (16) mm Hg and 132 (15) mm Hg, respectively, (mean difference = - 2.7 mm Hg; 95% CI -4.6 to -0.9; limits of agreement = -36 to 30 mm Hg) and the mean diastolic BP (DBP) was 70 (10) mm Hg and 69 (10) mm Hg, respectively (mean difference = - 0.9 mm Hg; 95% CI -2.1 to 0.3; limits of agreement = -22 to 20 mm Hg). Pearson correlation analysis showed modest correlations between the two types of BP measurements (SBP r=0.40, p<0.01; DBP r=0.45, p<0.01). Conclusion: The difference between clinic and research-grade BP was, on average, small, but differences at the individual level were often substantial.

Association of Parental Socioeconomic Status and Physical Activity with Development of Arterial Stiffness in Prepubertal Children

The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children (initial age 6–8 years) were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54–4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64–4.77) m/s) (p = 0.049). Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.

Association between central non-dipping pattern and platelet morphology in adults with type 1 diabetes without cardiovascular disease: a cross-sectional study

The non-dipping pattern is nighttime systolic blood pressure (SBP) fall of less than 10%. Several studies showed that the non-dipping pattern, increased mean platelet volume (MPV), and platelet distribution width (PDW) are associated with elevated cardiovascular risk. Hypertensives with the non-dipping pattern have higher MPV than the dippers but this relationship was never investigated among people with type 1 diabetes mellitus (T1DM). This study aimed to investigate the association between the central dipping pattern and platelet morphology in T1DM subjects. We measured the central and brachial blood pressure with a validated non-invasive brachial oscillometric device—Arteriograph 24—during twenty-four-hour analysis in T1DM subjects without diagnosed hypertension. The group was divided based on the central dipping pattern for the dippers and the non-dippers. From a total of 62 subjects (32 males) aged 30.1 (25.7–37) years with T1DM duration 15.0 (9.0–20) years, 36 were non-dippers. The non-dipper group had significantly higher MPV (MPV (10.8 [10.3–11.5] vs 10.4 [10.0–10.7] fl; p = 0.041) and PDW (13.2 [11.7–14.9] vs 12.3 [11.7–12.8] fl; p = 0.029) than dipper group. Multivariable logistic regression revealed that MPV (OR 3.74; 95% CI 1.48–9.45; p = 0.005) and PDW (OR 1.91; 95% CI 1.22–3.00; p = 0.005) were positively associated with central non-dipping pattern adjusting for age, sex, smoking status, daily insulin intake, and height. MPV and PDW are positively associated with the central non-dipping pattern among people with T1DM.

Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood

Metformin is widely used in pregnancy, despite lack of long-term safety for children. We hypothesised that metformin exposure in utero is associated with increased cardiovascular risk. We tested this hypothesis in a follow-up study of children born to obese mothers who had participated in a randomised controlled trial of metformin versus placebo in pregnancy (EMPOWaR). We measured body composition, peripheral blood pressure (BP), arterial pulse wave velocity and central haemodynamics (central BP and augmentation index) using an oscillometric device in 40 children of mean (SD) age 5.78 (0.93) years, exposed to metformin (n = 19) or placebo (n = 21) in utero. There were no differences in any of the anthropometric or vascular measures between metformin and placebo-exposed groups in univariate analyses, or after adjustment for potential confounders including the child’s behaviour, diet and activity levels. Post-hoc sample size calculation indicated we would have detected large clinically significant differences between the groups but would need an unfeasible large number to detect possible subtle differences in key cardiovascular risk parameters in children at this age of follow-up. Our findings suggest no evidence of increased cardiovascular risk in children born to obese mothers who took metformin in pregnancy and increase available knowledge of the long-term safety of metformin on childhood outcomes.

Improved Carotid Elasticity but Altered Central Hemodynamics and Carotid Structure in Young Athletes

Young athletes most often exceed the physical activity recommendations of the World Health Organization. Therefore, they are of special interest for investigating cardiovascular adaptions to exercise. This study aimed to examine the arterial structure and function of young athletes 12–17 years old and compare these parameters to reference values of healthy cohorts. Carotid intima-media thickness (cIMT), carotid diameter, cIMT÷carotid diameter-ratio (cIDR), arterial compliance (AC), elastic modulus (Ep), β stiffness index (β), and carotid pulse wave velocity (PWVβ) were determined using ultrasound in 331 young athletes (77 girls; mean age, 14.6 ± 1.30 years). Central systolic blood pressure (cSBP) and aortic PWV (aPWV) were measured using the oscillometric device Mobil-O-Graph. Standard deviation scores (SDS) of all parameters were calculated according to German reference values. The 75th and 90th percentiles were defined as the threshold for elevated cIMT and arterial stiffness, respectively. Activity behavior was assessed with the MoMo physical activity questionnaire, and maximum power output with a standard cardiopulmonary exercise test. One-sample t-tests were performed to investigate the significant deviations in SDS values compared to the value “0”. All subjects participated in competitive sports for at least 6 h per week (565.6 ± 206.0 min/week). Of the 331 young athletes, 135 (40.2%) had cIMT &gt;75th percentile, 71 (21.5%) had cSBP &gt;90th percentile, and 94 (28.4%) had aPWV&gt;90th percentile. We observed higher cIMT SDS (p &lt; 0.001), cIDR SDS (p = 0.009), and AC SDS (p &lt; 0.001) but lower β SDS (p &lt; 0.001), Ep SDS (p &lt; 0.001), and PWVβ SDS (p &lt; 0.001) compared to the reference cohort. The cSBP SDS (p &lt; 0.001) and aPWV SDS (p &lt; 0.001) were elevated. In conclusion, cIMT and cIDR were higher in young athletes than in a reference cohort. Furthermore, young athletes presented better carotid elasticity and lower arterial stiffness of the carotid artery. However, central arterial stiffness was higher compared to the reference cohort. The thickening of the carotid intima-media complex in combination with a reduction in arterial stiffness indicates a physiological adaptation to exercise in youth.

No significant association of serum klotho concentration with blood pressure and pulse wave velocity in a Chinese population

Klotho, an important anti-aging protein, may be related to elevated blood pressure (BP) and arterial stiffness. We aimed to investigate associations between the serum klotho concentration and peripheral/central BP and arterial stiffness based on the carotid–femoral pulse wave velocity (cfPWV) in a Chinese population. We invited all inhabitants aged ≥ 18 years in two Dali communities for participation. The SphygmoCor system was used to record radial arterial waveforms. Aortic waveforms were derived using a generalized transfer function. The central BP was assessed by calibrating the brachial BP, which was measured using an oscillometric device. The serum klotho concentration was measured using an enzyme-linked immunosorbent assay and logarithmically transformed. Of the 716 participants (mean age: 51.9 ± 12.6 years), 467 (65.2%) were women. The median serum klotho concentration was 381.8 pg/mL. The serum klotho concentration did not significantly differ between patients with and without hypertension (P > 0.05) and between those with and without arterial stiffness (cfPWV ≥ 10 m/s) (P > 0.05). After adjusting for confounders, the serum klotho concentration was not significantly associated with the peripheral or central BP (P > 0.05) and cfPWV (P > 0.05). Our data indicated that the serum klotho concentration was not associated with BP or cfPWV in the general Chinese population.