Hypercholesterolaemia plays a major causal role in atherogenesis and reduction of blood cholesterol is therefore a primary therapeutic target. Although great progress has been made in identifying pathogenic mechanisms of atherosclerosis, in particular with regard to the role of apolipoproteins and scavenger receptors, low density lipoprotein (LDL) oxidation, adhesion molecules, growth factors, interleukins, nitric oxide, and intracellular signalling in arterial cells [ 1–7], little is known about genes or other factors that determine the basic susceptibility to atherosclerosis in humans. Recent studies provided new insights by showing that the atherogenic process begins in fetal arteries and that the fetal onset of atherogenesis profoundly influences the rate of its progression throughout childhood and adolescence. The potential clinical implications of these findings will be discussed here.

Until recently, atherogenesis was thought to begin during late childhood, even though fatty streaks had occasionally been observed in younger childre n [8, 9]. A single fatty streak had also been reported in a human fetus with familial hypercholesterolaemia [ 10], but elevated maternal cholesterol levels during pregnancy were not considered to be a risk factor of atherosclerosis, because animal studies had indicated that the placenta is impermeable to large, cholesterolcarrying apolipoproteins [11], and because in the absence of heritable defects of the lipoprotein metabolism, cholesterol levels in term-newborns are not correlated with maternal cholesterol levels. However, a systematic morphometric analysis of crosssections through the entire aorta of premature human fetuses (fetal age 6· 21· 3 months) demonstrated that the formation of fatty streaks, the precursors of more advanced atherosclerotic lesions, is prevalent in all fetal aortas, and that their number and size is markedly increased in fetuses whose mothers were hypercholesterolaemic during pregnancy [ 12]. Fetal lesions contained elements typical of early atherosclerotic lesions, such as native and oxidized LDL and macrophages, and reached intimal medial ratios