Andersons pediatric cardiology 1975

lowest birth weight.419 Another proposed mechanism is the impairment of synthesis of elastin in the arterial wall.337 Superimposed circulatory imbalance, as happens in the donor twins in twin-twin transfusion syndrome,415 probably acts synergistically with growth restriction to cause the vascular programming, although the exact mechanism remains to be defined The exact mechanism of endothelial dysfunction in individuals with low birth weight is even more elusive Nutritional Issues The association between early growth restriction and arterial dysfunction highlights the potential importance of nutrition in antenatal and early postnatal life on long-term vascular programming In a recent mother-offspring study, higher consumption of oily fish by mothers in late pregnancy has been associated with lower aortic pulse-wave velocity measured in their children at the age of 9 years Leeson et al studied the relation between duration of breastfeeding and brachial artery distensibility in a young adult population-based cohort.420 They found an inverse relation between duration of breastfeeding and arterial distensibility even after adjusting for current lipid profile, body mass index, and social class A study in 10-year-old children also demonstrated a positive association between the duration of breastfeeding and stiffness of the aortofemoral arterial segment as determined by pulse-wave velocity.385 On the other hand, data from the Cardiovascular Risk in Young Finns Study suggest that adult men who had been breast-fed have better brachial endothelial function compared with those who had been formula-fed.421 It is important to realize, however, that there is to date little consistent evidence that breastfeeding influences subsequent mortality related to cardiovascular disease422 and that the current advice on breastfeeding practice has not been altered by these findings In children receiving long-term parenteral nutrition, a significant increase in the elastic modulus of the common carotid artery and impairment of brachial artery flow-mediated dilation have been demonstrated.423 Although the mechanisms are unclear, animal studies suggest that the infusion of lipid emulsions or high-concentration dextrose can cause endothelial damage and vascular remodeling.424,425 It remains unknown whether vascular dysfunction is reversible after the reestablishment of enteral feeding Childhood Vasculitides Kawasaki disease, a childhood vasculitis of unknown etiology, is the most common cause of acquired heart disease in children in developed countries (see Chapter 53) The inflammatory damage to coronary and other medium-sized arteries in the acute phase of the disease is well described.426 Long-term structural alteration and functional disturbance of the coronary arteries are also clearly documented.427–429 Increasingly, systemic arterial dysfunction is recognized in children with a history of Kawasaki long after the acute illness Impaired brachial artery flow-mediated dilation has been demonstrated in patients, even in those without early coronary arterial involvement, studied at a median of 11 years after the acute illness.430 Intravenous administration of vitamin C may improve the impaired flow-mediated dilation.431 An increase in circulating endothelial cells has also been found in patients with and without coronary artery aneurysms years after the acute illness.432 Increased stiffness of the carotid433,434 and brachioradial arteries435 occurs in a dose-dependent manner to the degree of coronary arterial involvement This corroborates the findings of reduced characteristic impedance and total peripheral arterial compliance in Kawasaki patients regardless of persistence of coronary artery aneurysms.436 Additionally, the mannose-binding lectin genotype437 and polymorphisms of the C-reactive protein and tumor necrosis factor-α genes438 may exert a modulating effect on arterial stiffness in the long term in these patients Chronic low-grade inflammation, as reflected by elevated high-sensitivity Creactive protein,439,440 in patients with coronary aneurysm formation has been associated positively with carotid arterial stiffness.439 There is histologic evidence of fibrointimal thickening and infiltration of lymphocytes and plasma cells in the coronary arterial walls in fatal cases of Kawasaki disease years after the apparent resolution of vascular inflammation and in the absence of early detectable coronary arterial abnormalities.441 Chronic activation of the monocyte chemoattractant protein-1/chemokine receptor CCR2 pathway and inducible nitric oxide synthase may play a role in this chronic low-grade inflammatory process.442 Positron emission tomography scanning provides in vivo evidence of ongoing inflammation of giant coronary and axillary aneurysms.443,444 This vascular inflammatory remodeling may be dampened by the use of statins.443 Marked acceleration of atherosclerosis is evident in a mouse model of Kawasaki disease.445 Although cross-sectional studies of carotid intima-media thickening in patients with Kawasaki disease have been conflicting, the finding of an increase in carotid intima-media thickening in patients with persistent coronary aneurysms appears to be a more consistent one.446,447 In the only longitudinal study performed to date, Dietz et al found an initial increase but with subsequent normalization of carotid intima-media thickness in patients without coronary aneurysms.448 On the other hand, patients with giant coronary aneurysms showed a trend toward persistent increase in carotid intima-media thickness Whether this long-term structural change of the artery represents premature atherosclerosis or a distinct type of vasculopathy continues to be a matter of debate Limited data exist for systemic arterial dysfunction in other types of childhood vasculitis Transient impaired of forearm vascular endothelium-dependent relaxation has been found in children during the acute phase of HenochSchönlein purpura.449 In children with polyarteritis nodosa, a chronic vasculitis characterized by recurrent episodes of inflammatory exacerbation, stiffening of the brachioradial artery with amplification during episodes of inflammatory exacerbation has been demonstrated.335 Endothelial microparticles have also been found to be significantly increased in children with systemic vasculitis and to correlate with disease activity score.450 Vasculopathies in Syndromal Disorders Patients with Marfan syndrome have increased aortic stiffness, as evidenced by the decreased distensibility and increased stiffness indexes,451–454 increased pulse-wave velocity,455 and decreased tissue Doppler-derived systolic and diastolic velocities of the aortic wall.456 The correlation between fibrillin-1 genotype and aortic stiffness in these patients is, however, poor.457 Endothelial dysfunction in Marfan syndrome may be related to a defective role of subendothelial fibrillin in endothelial cell mechanotransduction458 and downregulation of signaling of nitric oxide production,459 which contributes further to arterial stiffening Importantly, aortic stiffness has been shown to be an independent predictor of progressive aortic dilation460,461 and aortic dissection.461 β-Blocker therapy,455 angiotensin-converting enzyme inhibition,462 and losartan463,464 appear to reduce aortic stiffness, which may in turn slow aortic dilation and delay aortic root replacement, although robust data