Atherosclerosis begins in childhood or adolescence and progresses during the young adult years to cause clinical coronary heart disease (CHD) in middle-aged and older individuals. This article reviews evidence regarding the association of the major established CHD risk factors with atherosclerosis in adolescents and young adults, with emphasis on the findings of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Age, non-high-density lipoprotein cholesterol concentration, smoking, hypertension, obesity, and hyperglycemia are positively associated with atherosclerotic lesions, whereas female gender and high-density lipoprotein cholesterol concentration are negatively associated with lesions. The PDAY study developed a risk score that provides a weighted summary of the risk factor effects on advanced atherosclerosis. Although developed to predict advanced atherosclerotic lesions, the risk score is also associated with all stages of lesion severity, including the transition from normal tissue to the earliest anatomically detectable lesion. Application of the PDAY risk score to data from longitudinal studies of risk factors in young adults shows that early measurement of risk factors predicts atherosclerosis assessed noninvasively up to 15 years later, and that subsequent change in risk score during the 15-year interval also predicts atherosclerosis. These findings provide strong support for maintaining a low lifetime risk and for focusing on preventing atherosclerosis as the most effective way to prevent CHD. Risk-factor control beginning in the late teenage years will retard development of the earliest stage of atherosclerosis and its progression, and will reduce or delay occurrence of CHD. © 2008 National Lipid Association.
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