HIV-infected children had a vascular dysfunction in the absence of cardiovascular risk factors. In this short series, no additional detrimental effects were observed after a mean of 5 years of antiretroviral therapy.

Noninvasive assessment of vascular dysfunction in the pediatric population has taken advantage of the development of high-resolution ultrasound techniques. The most frequently used methods are the quantification of flow-mediated endotheliumdependent dilation of the brachial artery and measurement of the intima-media thickening of the carotid artery. Both reduced flow-mediated dilation and increased intima-media thickness have been proven to correlate with late cardiovascular events and/or mortality in adults. As these noninvasive methods can easily be applied in children, there have been recent investigations in high-risk pediatric patients harboring classical cardiovascular risk factors. Endothelial dysfunction and increased thickness of the intima media are currently observed in children with familial hypercholesterolemia, obesity, and type 1 diabetes mellitus. The association of early vascular dysfunction with a known risk factor is an important issue as these anomalies precede the formation of atherosclerotic plaques. Therefore, they may help in stratification of the risk for cardiovascular event and to better tailor therapeutic interventions in at risk children. Finally, these methods have been applied in specific pediatric populations, such as children with end-stage renal disease, chronic parenteral nutrition, HIV infection, and coarctation of the aorta. In these conditions, endothelial dysfunction and vascular remodeling are also present early in life and these data raise new possibilities in the understanding of the pathogenesis of atherosclerosis in these populations. Atherosclerosis begins in childhood as deposits of cholesterol and its esters, referred to as fatty streaks, in the intima of large muscular arteries. Evidence regarding the associations of adult coronary artery disease risk factors with atherosclerosis in young persons have been described (1). These observations raise implications for the long-range prevention of coronary artery disease, starting in the pediatric practice. Before the use of high-resolution ultrasound techniques to assess vascular function, anatomical and functional evidence for atherogenesis could only be recognized by invasive investigations or on postmortem examination (2). Today, these noninvasive methods are commonly used to assess endothelial function and to detect early anatomical evidence of atherogenesis in adult and pediatric populations. The most widely used test to evaluate endothelial function measures the vasodilator response to increased blood flow of the brachial artery (flow mediated vasodilatation) (3). Adult studies have demonstrated that the endothelial function of the peripheral circulation is closely related to that of the coronary circulation. The remodeling of the large arteries can be evaluated by the measure of the thickening of the intima and media of the common carotid arteries, or of the aorta (4). These approaches give an estimation of the local or regional function of the examined arterial bed. However, a more global evaluation of the physic...

The prevalence of germline mutations in paediatric pulmonary hypertension (PH) is poorly documented. The objective of this study was to determine the mutation frequency in PH genes in a paediatric cohort and describe the clinical characteristics of mutation carriers.The study involved 66 index cases with PH: 35 children with idiopathic pulmonary arterial hypertension (IPAH); five children with familial PAH (FPAH); three children with pulmonary veno-occlusive disease (PVOD); and 23 children with PAH associated with congenital heart disease (APAH-CHD).No mutations were found in the 23 children with APAH-CHD. In the 40 children with IPAH or FPAH, 12 mutations were found: five on BMPR2; four on ACVRL1; and three on TBX4. In the three PVOD cases, two carried the EIF2AK4 mutation. Mutation carriers had a more severe disease at diagnosis and more aggressive first-line therapy was required. The three patients with PVOD had a very severe disease at diagnosis and required a lung transplantation.The genetic architecture of paediatric PAH is enriched in ACVRL1 and TBX4 mutations compared to adult PAH, but further studies are required to confirm these results. Childhood-onset PAH in children carrying a mutation in one of the genes tested has a more severe presentation at diagnosis but a similar outcome to that observed in non-carriers.