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ObjectivesTo describe a well-established marker of cardiovascular risk, carotid intima–media thickness (IMT) and related measures (artery distensibility and elasticity) in children aged 11–12 years old and mid-life adults, and examine associations within parent–child dyads.DesignCross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian major cities and eight selected regional towns, February 2015 to March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1489 children (50.0% girls) and 1476 parents (86.8% mothers) with carotid IMT data were included. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata.Outcome measuresUltrasound of the right carotid artery was performed using standardised protocols. Primary outcomes were mean and maximum far-wall carotid IMT, quantified using semiautomated edge detection software. Secondary outcomes were carotid artery distensibility and elasticity. Pearson’s correlation coefficients and multivariable linear regression models were used to assess parent–child concordance. Random effects modelling on a subset of ultrasounds (with repeated measurements) was used to assess reliability of the child carotid IMT measure.ResultsThe average mean and maximum child carotid IMT were 0.50 mm (SD 0.06) and 0.58 mm (SD 0.05), respectively. In adults, average mean and maximum carotid IMT were 0.57 mm (SD 0.07) and 0.66 mm (SD 0.10), respectively. Mother–child correlations for mean and maximum carotid IMT were 0.12 (95% CI 0.05 to 0.23) and 0.10 (95% CI 0.03 to 0.21), respectively. For carotid artery distensibility and elasticity, mother–child correlations were 0.19 (95% CI 0.10 to 0.25) and 0.11 (95% CI 0.02 to 0.18), respectively. There was no strong evidence of father–child correlation in any measure.ConclusionsWe provide Australian values for carotid vascular measures and report a modest mother–child concordance. Both genetic and environmental exposures are likely to contribute to carotid IMT.

Background Central aortic SBP (cSBP) may have superior prognostic value compared with peripheral SBP (pSBP), but noninvasive cSBP measurement techniques have not been formally validated in children and adolescents. Method This study assessed the accuracy of two automated devices and the radial tonometry/transfer function method (RT-TF) for estimating central pressures and pulse pressure amplification (PPA) in this population, with adherence to validation guidelines for central pressure devices. In 69 children/adolescents aged 3-18 years undergoing clinically indicated aortic catheterization, high fidelity ascending aortic cSBP was measured with a micromanometer-tipped wire and compared with values from SphygmoCor XCEL, Mobil-O-Graph (systolic/diastolic calibration, MoG-C1, or mean/diastolic calibration, MoG-C2) and RT-TF. Reference intra-arterial pSBP was derived from the tonometry pulse calibrated to central mean/diastolic pressures. Results XCEL, MoG-C1 and MoG-C2 overestimated cSBP by 7.9 ± 6.8 mmHg (mean ± SD), 5.7 ± 10.3 mmHg, and 19.1 ± 14.9 mmHg, exceeding the validation cut-off (5 ± 8 mmHg). Brachial pSBP was also overestimated by XCEL (10.9 ± 8.4 mmHg) and Mobil-O-Graph (11.5 ± 12.3 mmHg). By contrast, central and brachial diastolic pressures were underestimated by the automated devices, albeit mostly within acceptable limits; pulse pressures were, therefore, substantially overestimated. Central-brachial PPA (4.5 ± 4.4 mmHg) was overestimated by XCEL (8.7 ± 3.2 mmHg) and MoG-C1 (11.1 ± 6.4 mmHg), but underestimated by MoG-C2 (-3.0 ± 6.6 mmHg). Given accurate pulse calibration, RT-TF achieved acceptable accuracy for cSBP (-0.2 ± 4.6 mmHg) and central-radial PPA (1.9 ± 5.1 mmHg). Conclusion In conclusion, XCEL and Mobil-O-Graph overestimated pSBP and cSBP in children and adolescents. cSBP can be obtained via the same transfer function used in adults, but accurate pressure pulse calibration is critical.Video Abstracts: http://links.lww.com/HJH/B222.

ObjectivesTo describe the epidemiology and parent–child concordance of vascular function in a population-based sample of Australian parent–child dyads at child age 11–12 years.DesignCross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven major Australian cities and eight regional towns or home visits, February 2015–March 2016.ParticipantsOf all participating CheckPoint families (n=1874), 1840 children (49% girls) and 1802 parents (88% mothers) provided vascular function data. Survey weights and methods were applied to account for LSAC’s complex sample design and clustering within postcodes and strata.Outcome measuresThe SphygmoCor XCEL assessed vascular function, generating estimates of brachial and central systolic blood pressure and diastolic blood pressure, central pulse pressure, augmentation index and carotid–femoral pulse wave velocity. Pearson’s correlation coefficients and multivariable linear regression models estimated parent–child concordance.ResultsHypertension was present in 3.9% of children and 9.0% of parents. Mean child and parent values for augmentation index were 4.5% (SD 11.6) and 21.3% (SD 12.3), respectively, and those for carotid–femoral pulse wave velocity were 4.48 m/s (SD 0.59) and 6.85 m/s (SD 1.14), respectively. Parent–child correlation for brachial systolic blood pressure was 0.20 (95% CI 0.15 to 0.24), brachial diastolic blood pressure 0.21 (95% CI 0.16 to 0.26), central systolic blood pressure 0.21 (95% CI 0.16 to 0.25), central diastolic blood pressure 0.21 (95% CI0.17 to 0.26), central pulse pressure 0.19 (95% CI 0.14 to 0.24), augmentation index 0.28 (95% CI 0.23 to 0.32) and pulse wave velocity 0.22 (95% CI 0.18 to 0.27).ConclusionsWe report Australian values for traditional and more novel vascular function markers, providing a reference for future population studies. Cross-generational concordance in multiple vascular function markers is already established by age 11–12 years, with mechanisms of heritability remaining to be explored.

The pathogenesis of Kawasaki disease (KD) remains unknown and there is accumulating evidence for the importance of the innate immune system in initiating and mediating the host inflammatory response. We compared innate immune responses in KD and toxic shock syndrome (TSS) participants more than two years after their acute illness with control participants to investigate differences in their immune phenotype. Toxic shock syndrome shares many clinical features with KD; by including both disease groups we endeavoured to explore changes in innate immune responses following acute inflammatory illnesses more broadly. We measured the in vitro production of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10 following whole blood stimulation with toll-like receptor and inflammasome ligands in 52 KD, 20 TSS, and 53 control participants in a case-control study. Analyses were adjusted for age, sex, and unstimulated cytokine concentrations. Compared to controls, KD participants have reduced IL-1ra production in response to stimulation with double stranded RNA (geometric mean ratio (GMR) 0.37, 95% CI 0.15, 0.89, p = 0.03) and increased IL-6 production in response to incubation with Lyovec™ (GMR 5.48, 95% CI 1.77, 16.98, p = 0.004). Compared to controls, TSS participants have increased IFN-γ production in response to peptidoglycan (GMR 4.07, 95% CI 1.82, 9.11, p = 0.001), increased IL-1β production to lipopolysaccharide (GMR 1.64, 95% CI 1.13, 2.38, p = 0.01) and peptidoglycan (GMR 1.61, 95% CI 1.11, 2.33, p = 0.01), and increased IL-6 production to peptidoglycan (GMR 1.45, 95% CI 1.10, 1.92, p = 0.01). Years following the acute illness, individuals with previous KD or TSS exhibit a pro-inflammatory innate immune phenotype suggesting a possible underlying immunological susceptibility or innate immune memory.

Objective: To assess whether reservoir pressure (Pres) in young individuals with a compliant aorta is uniform throughout the aorta, as has recently been reported in older adults with cardiovascular disease (1). Methods: High fidelity pressure was measured with a Verrata wire (Philips Volcano) in 5 aortic locations (ascending-to-abdominal) via pull-back in 11 children with a normal aorta (age 10.4 ± 4.9 years, mean ± SD). Pres was calculated using the ‘pressure-only’ approach (2), with exponential fitting over the whole of diastole (1) (WholeDia) or the period when pressure declined in an approximately exponential fashion (ExpDia). Results: ExpDia produced a better fit than WholeDia (R2=0.99 ± 0.01 vs 0.91 ± 0.11, P < 0.001). Pres amplitude (ΔPres) in the ascending aorta from WholeDia fitting (12.0 ± 4.1 mmHg) was less than with ExpDia fitting (19.0 ± 5.2, P = 0.001). The zero-flow asymptotic pressure (Pinf) obtained from the fitting procedure was negative (non-physiological) in 76% (WholeDia) and 44% (ExpDia) of recordings, but fixing Pinf to 37 mmHg (average of physiological values) had little effect on the resulting ΔPres. ΔPres varied by 5.7 ± 3.0 mmHg (WholeDia) and 7.3 ± 3.7 mmHg (ExpDia) between aortic locations (both P

Objective: The aims of this study in children were to 1) evaluate two brachial oscillometric devices for estimating central augmentation index (AIx) and reflection magnitude (RM), and 2) test whether AIx or RM are associated with left ventricular mass index (LVMI). Methods: Intra-aortic (IA) AIx was calculated from high-fidelity pressure measured with a Verrata wire (Philips Volcano) in 60 children (9.2 ± 4.7 years) with unobstructed aorta undergoing clinically-indicated catheterisation. AIx was also obtained from SphygmoCor XCEL (SC, AtCor) and/or Mobil-o-Graph (MB, IEM) brachial oscillometric devices. RM(IA) was calculated via wave separation using a representative normalised flow waveform obtained from MRI in a separate group of normal adolescents, RM(SC) via the triangulation method, and RM(MB) provided by the proprietary software. LVMI was estimated via echocardiography. Results: Invasive vs non-invasive AIx and RM are compared in the Table. AIx(IA) correlated weakly with AIx(SC) (R = 0.27, P = 0.04) but not AIx(MB) (P = 0.4). Neither RM(SC) nor RM(MB) correlated with RM(IA) (P = 0.13 and P = 0.96 respectively). RM(IA) was moderately correlated with AIx(IA) (R = 0.69, P < 0.001) and weakly correlated with AIx(SC) (R = 0.36, P = 0.007) but not AIx(MB) (P = 0.7). In a multivariable regression, height (P < 0.001) and RM (IA) (P = 0.04) were independently and positively associated with LVMI (adjusted R2 = 0.24), whereas there were no associations of any AIx or non-invasively estimated RM with LVMI. Conclusion: Central AIx and RM were poorly estimated by SC and MB in children. Unlike RM(IA), none of the non-invasive indices of wave reflection correlated with LVMI, likely due to inadequate estimation of the central pressure waveform shape in this age group.