Risk factors and development of atherosclerosis in childhood
- Sarah D de Ferranti, MD, MPH
Sarah D de Ferranti, MD, MPH
- Director, Preventive Cardiology Clinic
- Department of Cardiology
- Boston Children's Hospital
- Jane W Newburger, MD, MPH
Jane W Newburger, MD, MPH
- Commonwealth Professor of Pediatrics
- Harvard Medical School
Although cardiovascular disease (CVD) is generally manifest in adulthood, the process of atherosclerosis can begin early in childhood . For most children, atherosclerotic vascular changes are minor and can be minimized or even prevented with adherence to a healthy lifestyle. However, in some children, the process is accelerated because of the presence of identifiable risk factors (eg, obesity and hypertension) and/or specific diseases that are associated with premature CVD (eg, diabetes mellitus) [1,2].
The evidence linking atherosclerotic changes in childhood to CVD will be reviewed here. In addition, risk factors in childhood that are associated with early atherosclerosis and CVD will also be discussed (table 1).
Primary pediatric intervention to reduce or minimize atherosclerosis, and identifying and managing the child at risk for atherosclerosis, are discussed separately. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children" and "Overview of the management of the child at risk for atherosclerosis".)
ATHEROSCLEROTIC CHANGES IN CHILDHOOD
Overview — Evidence for the development of atherosclerosis in childhood includes autopsy studies showing atherosclerotic changes in the young, and noninvasive, indirect data showing vascular changes associated with adult cardiovascular disease (CVD).
In addition, these studies demonstrate an association between premature atherosclerosis and well-established adult CVD risk factors (eg, overweight/obesity, hypertension, dyslipidemia, and smoke exposure).
- Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011; 128 Suppl 5:S213.
- American Academy of Pediatrics. Cardiovascular risk reduction in high-risk pediatric populations. Pediatrics 2007; 119:618.
- Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 1998; 338:1650.
- McGill HC Jr, McMahan CA, Zieske AW, et al. Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol 2000; 20:1998.
- McGill HC Jr, McMahan CA. Determinants of atherosclerosis in the young. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Am J Cardiol 1998; 82:30T.
- McMahan CA, Gidding SS, Malcom GT, et al. Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis. Pediatrics 2006; 118:1447.
- Webber BJ, Seguin PG, Burnett DG, et al. Prevalence of and risk factors for autopsy-determined atherosclerosis among US service members, 2001-2011. JAMA 2012; 308:2577.
- McMahan CA, Gidding SS, Malcom GT, et al. Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study. Cardiovasc Pathol 2007; 16:151.
- Groner JA, Joshi M, Bauer JA. Pediatric precursors of adult cardiovascular disease: noninvasive assessment of early vascular changes in children and adolescents. Pediatrics 2006; 118:1683.
- Aggoun Y, Szezepanski I, Bonnet D. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children. Pediatr Res 2005; 58:173.
- Gaeta G, De Michele M, Cuomo S, et al. Arterial abnormalities in the offspring of patients with premature myocardial infarction. N Engl J Med 2000; 343:840.
- Atabek ME, Kurtoglu S, Pirgon O, Baykara M. Arterial wall thickening and stiffening in children and adolescents with type 1 diabetes. Diabetes Res Clin Pract 2006; 74:33.
- Davis PH, Dawson JD, Riley WA, Lauer RM. Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study. Circulation 2001; 104:2815.
- Li S, Chen W, Srinivasan SR, et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA 2003; 290:2271.
- Raitakari OT, Juonala M, Kähönen M, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 2003; 290:2277.
- Dawson JD, Sonka M, Blecha MB, et al. Risk factors associated with aortic and carotid intima-media thickness in adolescents and young adults: the Muscatine Offspring Study. J Am Coll Cardiol 2009; 53:2273.
- Juonala M, Magnussen CG, Venn A, et al. Influence of age on associations between childhood risk factors and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation 2010; 122:2514.
- Ryder JR, Dengel DR, Jacobs DR Jr, et al. Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children. J Pediatr 2016; 168:205.
- Alpert BS, Collins RT. Assessment of vascular function: pulse wave velocity. J Pediatr 2007; 150:219.
- Im JA, Lee JW, Shim JY, et al. Association between brachial-ankle pulse wave velocity and cardiovascular risk factors in healthy adolescents. J Pediatr 2007; 150:247.
- Li S, Chen W, Srinivasan SR, Berenson GS. Childhood blood pressure as a predictor of arterial stiffness in young adults: the bogalusa heart study. Hypertension 2004; 43:541.
- Urbina EM, Dolan LM, McCoy CE, et al. Relationship between elevated arterial stiffness and increased left ventricular mass in adolescents and young adults. J Pediatr 2011; 158:715.
- Urbina EM, Kimball TR, Khoury PR, et al. Increased arterial stiffness is found in adolescents with obesity or obesity-related type 2 diabetes mellitus. J Hypertens 2010; 28:1692.
- Urbina EM, Kimball TR, McCoy CE, et al. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation 2009; 119:2913.
- Juonala M, Viikari JS, Kähönen M, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study. Eur Heart J 2010; 31:1745.
- Koskinen J, Kähönen M, Viikari JS, et al. Conventional cardiovascular risk factors and metabolic syndrome in predicting carotid intima-media thickness progression in young adults: the cardiovascular risk in young Finns study. Circulation 2009; 120:229.
- Juonala M, Järvisalo MJ, Mäki-Torkko N, et al. Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation 2005; 112:1486.
- Juonala M, Viikari JS, Rönnemaa T, et al. Elevated blood pressure in adolescent boys predicts endothelial dysfunction: the cardiovascular risk in young Finns study. Hypertension 2006; 48:424.
- Hartiala O, Magnussen CG, Kajander S, et al. Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study. J Am Coll Cardiol 2012; 60:1364.
- Hartiala O, Kajander S, Knuuti J, et al. Life-course risk factor levels and coronary artery calcification. The Cardiovascular Risk in Young Finns Study. Int J Cardiol 2016; 225:23.
- Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation 2003; 107:2571.
- Wilkins JT, Li RC, Sniderman A, et al. Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study. J Am Coll Cardiol 2016; 67:193.
- Loria CM, Liu K, Lewis CE, et al. Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study. J Am Coll Cardiol 2007; 49:2013.
- Magnussen CG, Venn A, Thomson R, et al. The association of pediatric low- and high-density lipoprotein cholesterol dyslipidemia classifications and change in dyslipidemia status with carotid intima-media thickness in adulthood evidence from the cardiovascular risk in Young Finns study, the Bogalusa Heart study, and the CDAH (Childhood Determinants of Adult Health) study. J Am Coll Cardiol 2009; 53:860.
- Juhola J, Magnussen CG, Viikari JS, et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J Pediatr 2011; 159:584.
- May AL, Kuklina EV, Yoon PW. Prevalence of cardiovascular disease risk factors among US adolescents, 1999-2008. Pediatrics 2012; 129:1035.
- Saydah S, Bullard KM, Imperatore G, et al. Cardiometabolic risk factors among US adolescents and young adults and risk of early mortality. Pediatrics 2013; 131:e679.
- Friedemann C, Heneghan C, Mahtani K, et al. Cardiovascular disease risk in healthy children and its association with body mass index: systematic review and meta-analysis. BMJ 2012; 345:e4759.
- Baker JL, Olsen LW, Sørensen TI. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 2007; 357:2329.
- Batty GD, Calvin CM, Brett CE, et al. Childhood Body Weight in Relation to Cause-Specific Mortality: 67 Year Follow-up of Participants in the 1947 Scottish Mental Survey. Medicine (Baltimore) 2016; 95:e2263.
- Skinner AC, Perrin EM, Moss LA, Skelton JA. Cardiometabolic Risks and Severity of Obesity in Children and Young Adults. N Engl J Med 2015; 373:1307.
- Steinberger J, Daniels SR, Eckel RH, et al. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2009; 119:628.
- Morrison JA, Friedman LA, Gray-McGuire C. Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study. Pediatrics 2007; 120:340.
- Al-Shaikh AM, Abdullah MH, Barclay A, et al. Impact of the characteristics of patients and their clinical management on outcomes in children with homozygous familial hypercholesterolemia. Cardiol Young 2002; 12:105.
- Haney EM, Huffman LH, Bougatsos C, et al. Screening and treatment for lipid disorders in children and adolescents: systematic evidence review for the US Preventive Services Task Force. Pediatrics 2007; 120:e189.
- Ritchie SK, Murphy EC, Ice C, et al. Universal versus targeted blood cholesterol screening among youth: The CARDIAC project. Pediatrics 2010; 126:260.
- Lloyd-Jones DM, Nam BH, D'Agostino RB Sr, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA 2004; 291:2204.
- Raghuveer G, White DA, Hayman LL, et al. Cardiovascular Consequences of Childhood Secondhand Tobacco Smoke Exposure: Prevailing Evidence, Burden, and Racial and Socioeconomic Disparities: A Scientific Statement From the American Heart Association. Circulation 2016; 134:e336.
- Kavey RE, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2006; 114:2710.
- Goldstein BI, Carnethon MR, Matthews KA, et al. Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation 2015; 132:965.
- Mendelson MM, Lyass A, O'Donnell CJ, et al. Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study. JAMA Cardiol 2016; 1:26.
- Gaillard R. Maternal obesity during pregnancy and cardiovascular development and disease in the offspring. Eur J Epidemiol 2015; 30:1141.
- Ramakrishnan A, Lee LJ, Mitchell LE, Agopian AJ. Maternal Hypertension During Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis. Pediatr Cardiol 2015; 36:1442.
- Skilton MR, Viikari JS, Juonala M, et al. Fetal growth and preterm birth influence cardiovascular risk factors and arterial health in young adults: the Cardiovascular Risk in Young Finns Study. Arterioscler Thromb Vasc Biol 2011; 31:2975.
- Thompson JA, Regnault TR. In utero origins of adult insulin resistance and vascular dysfunction. Semin Reprod Med 2011; 29:211.
- ATHEROSCLEROTIC CHANGES IN CHILDHOOD
- Direct evidence from autopsy studies
- Indirect evidence
- - Longitudinal prospective studies
- RISK FACTORS
- Overweight and obesity
- Metabolic syndrome
- Family history
- Smoke exposure
- Special risk conditions
- Prenatal factors
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS