Arterial stiffness in preschool children

Arterial stiffness (AS) is recognised as a marker for the development of atherosclerotic diseases in adults. AS describes the loss of capability of an artery to react on pressure changes due to loss of elasticity; it is influenced by several parameters such as: male sex, hypertension, smoking, dyslipidaemia, chronic inflammatory disease, older age, increased weight, a lower height, low birth weight, higher gestational age and breastfeeding in the first year of life.1–5 AS happens through a complex interaction between dynamic and stable adaptations involving cellular elements and the extracellular matrix of the vascular wall.6–11 AS is expressed in many parameters, such as carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIX) of the aorta and the brachial artery. cfPWV is used as a direct marker for AS, AIX is used as a direct marker for wave reflection and an indirect marker for AS.12–14 Central measures of AS are strongly related to cardiovascular disease compared to measurements made in the peripheral arterial segments.13 Central systolic blood pressure (BP) is an important parameter describing AS and shows in several studies a strong correlation with an increased AS.13,14 cfPWV and AIX increase with ageing and both provide information about the status of the arterial system.14 In particular, aortic pulse wave velocity (PWV) has been shown as a predictor of cardiovascular events and all-cause mortality.15 In this issue of the journal, Maaike and colleagues investigated 168 healthy children, aged 3.3–4.1 years, and measured anthropometric data and recorded other determinants using a questionnaire. AS, expressed in aortic PWV and AIX, using a non-invasive oscillometric device (arteriograph) was registered. In 100 children, at least one valid AS measurement was obtained. The mean aortic PWV was 5.56 m/s, and the mean AIX of the aorta was 19.7 m/s. The AIX was significantly inversely associated with body height, with a regression coefficient of −0.78 (m/s)/cm. The AIX was not significantly associated with age, sex or (birth) weight. The authors identified height as the most important determinant of the AIX in preschool children.16 In a previous study, the authors showed that the influence of body height changes over time were probably due to a change in aorta growth rate.17 In other studies in childhood, using different devices, other authors also found evidence for age and weight as determinants of AS.1,18–19 The authors of that study found comparable AS in men and women, while previous studies (older age groups) found evidence for increased AS in men; and these differences might be influenced by hormonal – puberty-related changes.20,21 A recent meta-analysis indicated that obesity in children/adolescents is associated with greater AS. It was verified a positive relationship between arterial pressure and PWV independent of obesity.22 Increased AS is a complex phenomenon characterised by decreased complacency (distensibility) of the large arteries.23 The increased AS can manifest itself through an increase in pulse pressure and isolated systolic hypertension.24,25 Children with obesity have a higher risk of hypertension; however, the relationship between hypertension and AS in children is unclear.26 These changes related to AS are influenced by haemodynamic forces and extrinsic factors, such as hormones and inflammatory mediators, which may be linked to the balance of sodium and glucose.27–31 The loss or disorganisation of the elastin and its substitution by collagen determines the increase in the stiffness of the wall, with the imbalance of this system, which can be caused by pro-inflammatory substances, alterations in the inhibition or activation of metalloproteinases, and pressure overload leading to collagen overproduction and/or the reduction of elastin, thus contributing to the decrease in vascular distensibility.32–34 Stabouli et al., in a study of 138 consecutive young patients (age range 4–20 years) referred to the hypertension centre, reported that 10.6% of the patients had cfPWV values equal to or higher than the 95th percentile of the study population,35 and cfPWV was higher in hypertensive compared to the normotensive patients, classified by ambulatory BP levels even after adjustment for age and sex, suggesting that increased systolic BP variability is closely associated with AS in children and adolescents.35 Sen et al. reported in a study with 60 obese children and 60 age and sex-matched healthy controls, that obesity in children increases AS, which suggests that the joint effect of insulin resistance, serum leptin and adipokine levels and obesity can have a considerable impact on preclinical arterial changes and could play an important role in the pathophysiology of macrovascular disease.36 Gupta et al. studied aortic stiffness in children with Kawasaki disease. There was a noticeable trend towards lower aortic strain, higher pressure strain elastic modulus and normalised pressure strain elastic modulus in children in the study group.37 A trend towards lower distensibility and higher stiffness of the abdominal aorta was seen in cases compared with controls and significantly higher QT dispersion was seen in cases compared with controls.37 These dates could indicate a predictor of premature atherosclerosis in the long term. Dos and colleagues reported a study in children and adolescents with type 1 diabetes (T1DM). The authors identified that in T1DM increased pulse pressure is a marker for accelerated AS and ageing, and should be considered as an additional risk factor in the treatment of children with diabetes, and the elevated pulse pressure in children with T1DM may contribute to the high risk of the early development of atherosclerosis.38 Galler et al. examined the associations between AS indices and serum adiponectin concentrations in children and adolescents with T1DM. Children and adolescents with T1DM had increased AS and reduced arterial distensibility and arterial compliance; however, there were no associations between arterial functional alterations and adiponectin concentrations.39 Geerts and colleagues studied the relation between body size measures and vascular characteristics in healthy 5-year-old children. That study demonstrated that increased general body mass and particularly waist circumference and intra-abdominal fat are related to thicker and stiffer arteries already early in life.40 Sinha et al. compared large artery mechanical properties in children with non-dialysis stages of chronic kidney disease with those in children with normal renal function, examining the potential effect of BP components and the level of renal dysfunction.41 It has been observed that in children with chronic non-dialysed renal disease, changes in the elastic properties of the carotid artery are mainly related to artery pressure and not to glomerular renal function.41 In a recent study the authors compared observed PWVcf assessed by applanation tonometry in children enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. In this study of children with mild kidney dysfunction, AS was comparable to that of normal children.42 In conclusion, the article by Hidvegi and colleagues17suggests that height is the determinant of the AIX in the population studied. Of course, additional research is necessary to assess whether weight, and its association with dyslipidaemia, corpuscle mass index, waist circumference, BP, diabetes, metabolic syndrome and cardiovascular disease are related to AS in preschool children, and in which these changes related to AS in preschool may benefit from preventive measures or therapeutic interventions. The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. The author(s) received no financial support for the research, authorship and/or publication of this article.