Atherosclerosis 208 (2010) 501–505 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Cardiovascular risk factors and non-invasive assessment of subclinical atherosclerosis in youth K.M. Morrison ∗ , L. Dyal, W. Conner, E. Helden, L. Newkirk, S. Yusuf, E. Lonn Mc Master University, HSC 3A59, 1200 Main Street W, Hamilton, ON, L8N 3Z5, Canada article info Article history: Received 30 March 2009 Received in revised form 25 June 2009 Accepted 13 July 2009 Available online 23 July 2009 Keywords: Carotid intima media thickness Children Hyperlipidemia Obesity Determinants Family history abstract Our understanding of the natural history of atherosclerosis in childhood and its response to cardiovas- cular (CV) risk factor reduction have been hampered by the lack of a reliable, non-invasive measure of atherosclerosis. Carotid intima media thickness (IMT), a surrogate marker of atherosclerosis in adults, is increased in youth heterozygous for familial hypercholesterolemia (FH) and declines with lipid low- ering pharmacotherapy. The age at which vascular changes can be reliably identified using IMT and the influence of CV risk factors beyond FH on IMT remains unclear. Objective: To examine the influence of demographic, family history, anthropometric characteristics and traditional CV risk factors on IMT in children 5–16 years of age (mean age 11 year). Methods: In a cross-sectional study, we assessed IMT in 148 children (51 with elevated low density lipoprotein (LDL)-cholesterol, 44 with overweight and 53 controls). Measures included: family history of premature coronary heart disease (CHD), physical activity, pubertal stage, smoking history, fasting glucose, insulin, lipid profile, apolipoproteins A1 and B, anthropometry, blood pressure and IMT. Results: The groups were similar for age and family history of premature CHD. Compared to controls, average maximum IMT (0.403 ± 0.04 vs 0.387 ± 0.029) and average mean IMT were elevated in the hyper- lipidemia group (p < 0.05), but not in the overweight group (max IMT 0.393 ± 0.034; p vs control = 0.17). Using multiple regression modelling, age, family history of premature CHD and apoliprotein A1 and B predicted 17% of the variability in IMT. No measure of adiposity predicted IMT. Conclusion: Age is an important predictor of IMT in youth. Among traditional CV risk factors, dyslipidemia and family history of premature CHD are independent predictors of IMT. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Although the clinical manifestations of atherosclerosis are present in adulthood, early atherosclerotic change is apparent in youth studied post-mortem and the extent of atherosclerosis is related to the presence of cardiovascular (CV) risk factors [1]. Thus, primary prevention of atherosclerosis should begin with youth, but our understanding of its natural history and the influence of CV risk factor reduction in childhood has been hindered by the lack of a reliable non-invasive measure of atherosclerosis. In adults, carotid intima media thickness (IMT) is a reliable, non-invasive surrogate for the anatomic extent of atherosclerosis and predicts future risk for coronary heart disease (CHD) and stroke even after controlling for traditional CV risk factors [2–6]. IMT is increased in adolescents with heterozygous familial hypercholesterolemia (FH) [7–9], and progression is slowed by lipid lowering therapy after 2 years [10]. In children under 10 years of age ∗ Corresponding author. Tel.: +1 905 521 2100x75702; fax: +1 905 308 7548. E-mail address: kmorrison@mcmaster.ca (K.M. Morrison). increased IMT was not seen [11], suggesting that the identification of increased IMT may be age dependent. Adolescents with other dis- orders that increase their CV risk, including obesity [12,13], hyper- tension [14] and type 1 diabetes [15] had increased IMT in some, but not in all studies [16,17]. The age at which vascular structural changes can be identified using non-invasive imaging techniques, and the determinants of IMT in youth remain poorly defined. We compared IMT in children 5–17 years of age with elevated low density lipoprotein (LDL)-cholesterol or overweight to lean controls with normal lipid profiles. The influence of age, gender, pubertal status, body size, body fat, CV risk factors and family his- tory of premature CHD on IMT was assessed. 2. Methods 2.1. Subjects Study participants were recruited from the Pediatric Lipid Clinic (n =51) and the Children’s Exercise and Nutrition Cen- tre at McMaster Children’s Hospital (MCH) in Hamilton, Canada (n = 44) and during well-child visits in a Pediatrician’s office (n = 53) 0021-9150/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2009.07.034