HDL-Cholesterol, Blood Pressure, and Asymmetric Dimethylarginine Are Significantly Associated With Arterial Wall Thickness in Children

Abstract

Objective-Atherosclerosis is found at autopsy in the arteries of adolescents and young adults. Arterial wall thickening may be assessed in vivo by ultrasound measurement of the carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis. As the determinants of arterial wall thickness in childhood are unknown, we assessed the influence of cardiovascular risk factors on CIMT in 8-year-old children. Methods and Results-A community-based sample of 405 children (age 8.0Ϯ0.1 years, 49% girls) had anthropometry, family history, blood pressure (BP), and CIMT measured. A blood sample was collected for HDL and non-HDL cholesterol, apolipoproteins A1 and B, high-sensitivity C-reactive protein, bilirubin, and asymmetric dimethylarginine (ADMA, an endogenous nitric oxide inhibitor Key Words: HDL-cholesterol Ⅲ asymmetric dimethylarginine Ⅲ pediatric Ⅲ intima-media thickness Ⅲ blood pressure S tructural evidence of early atherosclerosis is commonly found in adolescents and young adults when their arteries are examined at autopsy. The extent of these lesions increases with age and with the number and severity of traditional cardiovascular risk factors. 1,2 B-mode ultrasound examination of the arterial wall, performed during life, produces a characteristic image that correlates with the histological intima-media complex. 3 In adults, the carotid artery intimamedia thickness (CIMT) is correlated with coronary and carotid atherosclerosis and is a significant predictor of future cardiovascular events. 4 For these reasons, CIMT has been used in numerous cross-sectional and intervention studies as a surrogate end point for atherosclerosis. 5 Although high-risk children, such as those with familial hypercholesterolemia and type 1 diabetes mellitus, have increased CIMT compared with healthy controls 6,7 and risk factors present in childhood are associated with CIMT in adult life, 8,9 the factors that influence CIMT in healthy children are largely unknown. We undertook a study of 8-year-old boys and girls to explore the effects of cardiovascular risk factors on arterial wall thickness in early childhood. We hypothesized that the traditional cardiovascular risk factors, such as blood pressure, lipoprotein levels, family history, and relative body weight would have an important effect on arterial wall thickness in healthy children in the first decade of life. We aimed to examine the extent to which markers of inflammation or endothelial dysfunction influenced arterial structural changes in childhood. The effects of prenatal factors, such as birth weight, pregnancy-induced hypertension, and preeclampsia, and maternal cigarette usage were also assessed.

Weight Gain in Infancy and Vascular Risk Factors in Later Childhood

“…Nonetheless, participants had an anthropometric and cardiovascular risk profile similar to that from an unselected community-based population of a similar age from the same geographical area. 7,32 We cannot exclude potential residual confounding by socioeconomic status; however, additional adjustment for paternal education, maternal and paternal employment, and maternal and paternal country of birth did not materially alter our results. Finally, we analyzed a sample of 395 subjects from the 616 originally randomized subjects.…”

“…7,8 In particular, we were interested in assessing carotid intima-media thickness (IMT), a marker of atherosclerosis extent and an independent determinant of cardiovascular risk in adulthood. 9 We therefore hypothesized that early weight gain, from birth to age 18 months would be associated with incident obesity, higher blood pressure, an adverse lipid profile, systemic inflammation, and arterial wall thickening in later childhood.…”

Osteoprotegerin is Associated With Endothelial Function and Predicts Early Carotid Atherosclerosis in Patients With Coronary Artery Disease

“…29,30) Ayer, et al 31) showed higher levels of ADMA and a lower HDL cholesterol level to be significantly associated with a greater CIMT in early childhood. Additionally, the present study showed that OPG plays an important role in the pathogenesis of early carotid atherosclerosis in patients with CAD.…”

Family History in Public Health Practice: A Genomic Tool for Disease Prevention and Health Promotion

“…Although most chronic conditions do not manifest until adulthood, an increasing number of studies indicate that children and adolescents with family histories of some conditions already show preclinical signs of these conditions (98). For example, children with a strong family history of coronary artery disease may show early signs of atherosclerosis, such as elevated markers of inflammation and plaque instability and increased carotid intima media thickness (4,39,93). However, the use of family history to assess the risk that children might develop chronic diseases as adults has not been thoroughly evaluated.…”