Diseases associated with 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) generally manifests in adulthood, the process of atherosclerosis can begin in early 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 (table 1) .
Pediatric diseases that are associated with an increased risk of accelerated atherosclerosis and CVD will be discussed here. Identification and management of children at risk for atherosclerosis are discussed separately. (See "Risk factors and development of atherosclerosis in childhood" and "Overview of the management of the child at risk for atherosclerosis".)
RISK STRATIFICATION BASED ON SPECIFIC DISEASES
Specific disease states are associated with early cardiovascular disease (CVD) and accelerated atherosclerosis. In a scientific statement from the American Heart Association (AHA), a panel of experts reviewed the literature on premature cardiovascular disease in children and established a disease risk stratification schema for coronary artery disease (CAD), which was revised into a two-tier schema by the National Heart, Lung, and Blood Institute (NHLBI) panel in 2011 (algorithm 1) [2,3].
This schema separates diseases into high and moderate risk categories for CVD as follows:
●High risk conditions – High risk conditions are associated with pathologic or clinical evidence of CAD before 30 years of age, including the following (see 'High-risk conditions' below):
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- 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.
- 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.
- Haller MJ, Stein J, Shuster J, et al. Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes 2007; 8:193.
- Haller MJ, Stein JM, Shuster JJ, et al. Pediatric Atorvastatin in Diabetes Trial (PADIT): a pilot study to determine the effect of atorvastatin on arterial stiffness and endothelial function in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2009; 22:65.
- Nayir A, Bilge I, Kiliçaslan I, et al. Arterial changes in paediatric haemodialysis patients undergoing renal transplantation. Nephrol Dial Transplant 2001; 16:2041.
- Litwin M, Grenda R, Prokurat S, et al. Patient survival and causes of death on hemodialysis and peritoneal dialysis--single-center study. Pediatr Nephrol 2001; 16:996.
- Mitsnefes MM, Kimball TR, Witt SA, et al. Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 2003; 107:864.
- Hussein G, Bughdady Y, Kandil ME, et al. Doppler assessment of brachial artery flow as a measure of endothelial dysfunction in pediatric chronic renal failure. Pediatr Nephrol 2008; 23:2025.
- Litwin M, Wühl E, Jourdan C, et al. Evolution of large-vessel arteriopathy in paediatric patients with chronic kidney disease. Nephrol Dial Transplant 2008; 23:2552.
- Covic A, Mardare N, Gusbeth-Tatomir P, et al. Increased arterial stiffness in children on haemodialysis. Nephrol Dial Transplant 2006; 21:729.
- Bakiler AR, Yavascan O, Harputluoglu N, et al. Evaluation of aortic stiffness in children with chronic renal failure. Pediatr Nephrol 2007; 22:1911.
- Fassett RG, Ball MJ, Robertson IK, et al. The Lipid lowering and Onset of Renal Disease (LORD) Trial: a randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease. BMC Nephrol 2008; 9:4.
- Pahl E, Zales VR, Fricker FJ, Addonizio LJ. Posttransplant coronary artery disease in children. A multicenter national survey. Circulation 1994; 90:II56.
- Dent CL, Canter CE, Hirsch R, Balzer DT. Transplant coronary artery disease in pediatric heart transplant recipients. J Heart Lung Transplant 2000; 19:240.
- Kuhn MA, Jutzy KR, Deming DD, et al. The medium-term findings in coronary arteries by intravascular ultrasound in infants and children after heart transplantation. J Am Coll Cardiol 2000; 36:250.
- Dalla Pozza R, Bechtold S, Urschel S, et al. Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease. J Pediatr 2007; 151:239.
- Ilowite NT, Copperman N, Leicht T, et al. Effects of dietary modification and fish oil supplementation on dyslipoproteinemia in pediatric systemic lupus erythematosus. J Rheumatol 1995; 22:1347.
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- Patel K, Wang J, Jacobson DL, et al. Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus. Circulation 2014; 129:1204.
- Abd-Elmoniem KZ, Unsal AB, Eshera S, et al. Increased coronary vessel wall thickness in HIV-infected young adults. Clin Infect Dis 2014; 59:1779.
- Idris NS, Grobbee DE, Burgner D, et al. Effects of paediatric HIV infection on childhood vasculature. Eur Heart J 2016; 37:3610.
- Ordoñez JD, Hiatt RA, Killebrew EJ, Fireman BH. The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int 1993; 44:638.
- Radhakrishnan J, Appel AS, Valeri A, Appel GB. The nephrotic syndrome, lipids, and risk factors for cardiovascular disease. Am J Kidney Dis 1993; 22:135.
- Mulrooney DA, Yeazel MW, Kawashima T, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009; 339:b4606.
- Haddy N, Diallo S, El-Fayech C, et al. Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study. Circulation 2016; 133:31.
- Shankar SM, Marina N, Hudson MM, et al. Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group. Pediatrics 2008; 121:e387.
- Neville KA, Cohn RJ, Steinbeck KS, et al. Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors. J Clin Endocrinol Metab 2006; 91:4401.
- Green DM, Hyland A, Chung CS, et al. Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. J Clin Oncol 1999; 17:3207.
- Oeffinger KC, Mertens AC, Sklar CA, et al. Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2003; 21:1359.
- Birkebaek NH, Fisker S, Clausen N, et al. Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood. Med Pediatr Oncol 1998; 30:351.
- Lipshultz SE, Lipsitz SR, Hinkle AS, et al. Cardiovascular status, subsequent risk, and associated factors in long-term survivors of childhood cancer in a population-based study. Circulation 2005; 112 (Suppl 2):476.
- Steinberger J, Sinaiko AR, Kelly AS, et al. Cardiovascular risk and insulin resistance in childhood cancer survivors. J Pediatr 2012; 160:494.
- Pinto NM, Marino BS, Wernovsky G, et al. Obesity is a common comorbidity in children with congenital and acquired heart disease. Pediatrics 2007; 120:e1157.
- Roberts WC. Major anomalies of coronary arterial origin seen in adulthood. Am Heart J 1986; 111:941.
- Click RL, Holmes DR Jr, Vlietstra RE, et al. Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival--a report from the Coronary Artery Surgery Study. J Am Coll Cardiol 1989; 13:531.
- Ou P, Mousseaux E, Azarine A, et al. Detection of coronary complications after the arterial switch operation for transposition of the great arteries: first experience with multislice computed tomography in children. J Thorac Cardiovasc Surg 2006; 131:639.
- Pedra SR, Pedra CA, Abizaid AA, et al. Intracoronary ultrasound assessment late after the arterial switch operation for transposition of the great arteries. J Am Coll Cardiol 2005; 45:2061.
- Gagliardi MG, Adorisio R, Crea F, et al. Abnormal vasomotor function of the epicardial coronary arteries in children five to eight years after arterial switch operation: an angiographic and intracoronary Doppler flow wire study. J Am Coll Cardiol 2005; 46:1565.
- Pasquali SK, Marino BS, Pudusseri A, et al. Risk factors and comorbidities associated with obesity in children and adolescents after the arterial switch operation and Ross procedure. Am Heart J 2009; 158:473.
- Vriend JW, de Groot E, de Waal TT, et al. Increased carotid and femoral intima-media thickness in patients after repair of aortic coarctation: influence of early repair. Am Heart J 2006; 151:242.
- RISK STRATIFICATION BASED ON SPECIFIC DISEASES
- HIGH-RISK CONDITIONS
- Diabetes mellitus
- Chronic kidney disease
- Cardiac transplantation
- Kawasaki disease
- MODERATE-RISK CONDITIONS
- Chronic inflammatory diseases
- HIV infection
- Nephrotic syndrome
- Depressive and bipolar disorders
- OTHER CONDITIONS
- Familial hypercholesterolemia
- Childhood cancer
- Congenital heart disease
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- INFORMATION FOR PATIENTS