Review Early atherosclerosis in childhood: Diagnostic approaches and therapeutic strategies Marietta Charakida, Dimitris Tousoulis * , Christodoulos Stefanadis Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece Received 18 March 2005; received in revised form 20 May 2005; accepted 4 June 2005 Available online 14 July 2005 Abstract The long preclinical phase of atherosclerosis involves the interaction of genetic and environmental factors that modulate the progression of disease from early life. Injury to the endothelium is a critical step in atherosclerotic process. Conventional and novel risk factors for coronary artery disease operate from early in life. Noninvasive methods, using mostly ultrasound techniques, have enabled the assessment of early functional and structural arterial disease progression even from the first decade of life. These measures have been shown to be good surrogate markers for atherosclerotic disease progression and future clinical cardiovascular events. Lifestyle and dietary modifications as well as pharmacological interventions have beneficial effects in prevention and restoration of the early arterial changes. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Endothelium; Atherosclerosis; Childhood; Risk factors 1. Introduction Atherosclerosis, the major cause of coronary heart disease, manifests clinically in middle and late adulthood. However, it is well known that this disease has a very long asymptomatic phase of development, which begins very early in life, often during childhood. Postmortem studies in children documented the presence of fatty streaks by the end of first decade of life and in the context of maternal hypercholesterolemia during fetal life suggesting that there is no lower limit for atherogenesis [1]. Both intrinsic characteristics and exposure to risk factors have instrumental role in the development of atheroscle- rosis. Anatomical and ultrasound evidence from population studies have shown that cardiovascular risk factors, when present in childhood, have a detrimental impact on the vascular endothelium and accelerate disease progression during childhood and adulthood [2–4]. This review will describe the methods available for studying preclinical atherosclerotic vascular changes, the determinants of the early disease progression, their impact on the vascular phenotype and also strategies developed for restoration in the young. 2. Non-invasive methods to assess preclinical atherosclerosis The endothelium has a key role in early atherogenesis acting as a transducer of circulatory signals and regulating inflammation, growth factors, cell adhesion, thrombosis and vascular tone of the underlying smooth muscle. Injury to the endothelium is one of the earliest manifestations of subclinical atherosclerosis. Several non-invasive tests appli- cable for studies in children and young adults are now available and may provide assessment of the peripheral arterial function and structure (Table 1). 2.1. Functional measures In childhood, the non-invasive ultrasound assessment of the responsiveness of the arterial endothelium to changes in 0167-5273/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2005.06.010 * Corresponding author. Tel.: +30 210 7782446; fax: +30 210 7784590. E-mail address: drtousoulis@hotmail.com (D. Tousoulis). International Journal of Cardiology 109 (2006) 152 – 159 www.elsevier.com/locate/ijcard