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Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)

Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)
Authors:
Jacob C Hartz, MD, MPH
Sarah D de Ferranti, MD, MPH
Section Editor:
David R Fulton, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Apr 2025. | This topic last updated: Apr 29, 2025.

INTRODUCTION — 

Atherosclerotic vascular changes can begin in early childhood, setting the stage for atherosclerotic cardiovascular disease (ASCVD) events in adulthood. For most children, atherosclerotic vascular changes can be minimized or even prevented with adherence to a healthy lifestyle. However, in some children, the atherosclerotic process is accelerated because of underlying conditions and/or identifiable risk factors (table 1).

The evidence linking atherosclerotic changes in childhood to ASCVD later in life will be reviewed here. Related topics include:

●(See "Overview of the management of the child or adolescent at risk for premature atherosclerotic cardiovascular disease (ASCVD)".)

●(See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis".)

●(See "Dyslipidemia in children and adolescents: Management".)

●(See "Familial hypercholesterolemia in children".)

●(See "Hypertension in children and adolescents: Evaluation".)

●(See "Hypertension in children and adolescents: Nonemergency treatment".)

ASSOCIATION BETWEEN PEDIATRIC RISK FACTORS AND ADULT ASCVD — 

Evidence for the development of atherosclerosis in childhood includes:

●Autopsy studies showing atherosclerotic changes in the young (see 'Evidence from autopsy studies' below)

●Studies using noninvasive imagining to evaluate vascular changes in children, adolescents, and young adults (see 'Evidence of subclinical atherosclerosis' below)

●Longitudinal studies showing associations between ASCVD risk factors (eg, overweight/obesity, hypertension, dyslipidemia, and smoke exposure) in childhood/adolescence and development of clinical ASCVD in adulthood (see 'Evidence linking childhood risk factors to ASCVD events in adulthood' below)

In addition, ASCVD risk factors often track into adulthood and children with ASCVD risk factors are more likely to be at-risk adults.

These data, along with evidence from adult studies, are the basis for promoting healthy behaviors in childhood to prevent and reduce risk factors associated with premature atherosclerosis and, by extension, overt ASCVD. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children" and "Overview of the management of the child or adolescent at risk for premature atherosclerotic cardiovascular disease (ASCVD)".)

Evidence from autopsy studies — Autopsy studies in children and young adults who have died of noncardiovascular causes demonstrate that atherosclerosis can begin in childhood. Findings in these studies included fatty streaks (accumulation of lipid-filled macrophages within the intima of the artery that are early atherosclerotic changes) and fibrous plaques (a more advanced stage of atherosclerosis).

Examples of these studies include:

●In the Bogalusa Heart Study, autopsies performed in 204 young subjects (2 to 39 years of age, mean age 19.6 years) demonstrated fatty streaks in 50 percent of cases between 2 and 15 years of age and in 85 percent of older subjects between 21 and 39 years of age [1]. The prevalence of raised fibrous plaques in the aorta and coronary arteries also increased with age from approximately 20 percent in subjects between 2 and 15 years of age to 70 percent in those between 26 and 39 years of age. The prevalence and the extent of atherosclerosis found in the aorta and coronary arteries were greater with increasing body mass index (BMI), blood pressure measurements, and levels of serum total cholesterol and low-density lipoprotein cholesterol (LDL-C). The degree of atherosclerotic changes increased with worsening severity and greater numbers of risk factors.

●The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study examined the right coronary arteries and aortas in autopsies of 2876 individuals between 15 and 34 years of age [2,3]. In subjects who were 15 to 19 years of age, raised fatty streaks were present in 10 percent of coronary arteries and 30 percent of aortas. The extent of fatty streaks increased with increasing age, elevated blood pressure, higher serum LDL-C, and lower serum high-density lipoprotein cholesterol. Female patients lagged by five years behind male patients in the progression of the extent of raised lesions in the right coronary arteries. In a subsequent report, individuals with early and more severe atherosclerotic changes were more likely to have had one or more ASCVD risk factor (including dyslipidemia, obesity, hyperglycemia, hypertension, or smoking) [4]. The prevalence of risk factors among adolescents and young adults in the PDAY study mirror that of population-based data of general pediatric population [5].

●A subsequent study examined autopsy reports of 3832 United States military service members who died in combat or due to unintentional injury between 2001 and 2011 [6]. Mean age was 26 (range 18 to 59) years, and 98 percent were male. The presence of any coronary atherosclerosis was noted in 8.5 percent of deceased service members, with 2.3 percent having severe atherosclerosis (defined as ≥50 percent narrowing of one or more vessels). Those with any atherosclerosis had a higher prevalence of dyslipidemia, hypertension, and obesity. Interestingly, smoking did not appear to be a contributor in this study.

Evidence of subclinical atherosclerosis — Studies using noninvasive imaging to evaluate vascular changes in children and adolescents provide indirect evidence for early development of atherosclerosis, which is associated with ASCVD in adulthood [7,8]. These indirect measures include changes in vessel anatomy (ie, increased intima-media thickness [IMT] and coronary calcification), mechanical changes (ie, decreased arterial distensibility or increased stiffness), and physiologic changes (ie, decreased flow mediated vasodilatation) [7].

●Carotid IMT (CIMT) – Adults with increased CIMT detected by ultrasonography have a higher likelihood of experiencing an ASCVD event. Among children and adolescents, increased CIMT may be seen in patients with certain high-risk conditions (eg, familial hypercholesterolemia [FH]) and in children with ASCVD risk factors (ie, family history of premature ASCVD, overweight, dyslipidemia, hypertension, diabetes mellitus [DM]) [9-19]. Dyslipidemia in childhood and adolescence is associated with increased CIMT in adulthood, even after accounting for sex, obesity, and hypertension [13,20,21]. (See "Overview of possible risk factors for cardiovascular disease", section on 'Arterial intima-media thickness'.)

●Arterial stiffness – Arterial stiffness can be measured as pulse wave velocity (PWV), which is the speed at which an aortic pulse travels between arteries in the upper body to the lower body. In adults, increased arterial stiffness is associated with a higher likelihood of ASCVD. PWV measurements vary among adolescents and young adults based upon age and sex [22]. A high burden of ASCVD risk factors (ie, high BMI, hypertension, hypertriglyceridemia, glucose intolerance) is associated with higher PWV in adolescents and young adults, even after adjusting for age and sex [22-24]. Increased arterial stiffness can lead to cardiac remodeling and is associated with higher left ventricular mass in adolescents and young adults [25]. In one study of 670 adolescents and young adults (age range 10 to 24 years) stratified into three groups based upon BMI (lean [BMI <85th percentile], overweight and obese [BMI ≥85th percentile], and overweight/obese with type 2 DM), there was a progressive increase in PWV from the lean group to the obese and obese/type 2 DM groups [26]. (See "Overview of possible risk factors for cardiovascular disease", section on 'Arterial stiffness'.)

●Flow-mediated dilation – Flow-mediated dilation (FMD) measures the endothelial response to an adverse stimulus (eg, ischemia induced by an inflated blood pressure cuff) by brachial artery ultrasonography (also referred to as brachial artery reactivity). Lower brachial artery reactivity has been identified in children with obesity [14], a family history of premature coronary disease [15], type 1 DM, and Kawasaki disease with aneurysms. (See "Coronary endothelial dysfunction: Clinical aspects", section on 'Noninvasive testing'.)

Numerous longitudinal studies have demonstrated an association between the traditional ASCVD risk factors (ie, dyslipidemia, obesity, hypertension, smoke exposure, and DM) during childhood and evidence of early atherosclerotic changes in adulthood based upon one or more of the above measures (CIMT, PWV, and/or FMD).

●Bogalusa study – In a cohort of 486 adults (age range 25 to 37 years), childhood measurements of LDL-C levels and BMI positively predicted CIMT [10].

●Muscatine study – In a cohort of 725 adults (age range 33 to 42 years), childhood total cholesterol levels and BMI were predictors of CIMT in adulthood [9].

●Cardiovascular Risk in Young Finns study – In a cohort of Finnish patients followed for >25 years, CIMT increased as the number of ASCVD risk factors increased [27]. In particular, elevated childhood levels of LDL-C and insulin, as well as obesity, were predictive of increased CIMT [28]. In subsequent studies, carotid artery elasticity decreased as the number of childhood ASCVD risk factors increased and FMD was lower in male patients who had hypertension during adolescence [29,30]. In this cohort, exposure to ASCVD risk factors over time correlated with the extent of coronary artery calcification by computed tomography [31,32]. In follow-up studies of this cohort at age 34 to 49 years, the number of early life ASCVD risk factors correlated with worse midlife cognitive function [33,34].

●Coronary Artery Risk Development in Young Adults (CARDIA) study – In a cohort of patients initially recruited at 18 to 30 years of age and followed for 15 years, baseline ASCVD risk factors (smoking, dyslipidemia, glucose intolerance, hypertension) were associated with increased risk of coronary artery calcification later in life [35,36].

Evidence linking childhood risk factors to ASCVD events in adulthood — Evidence linking childhood risk factors to ASCVD events in adulthood comes from several i3C (international Childhood Cardiovascular Cohort Consortium) studies that analyzed combined data from multiple prospective studies [13,37,38].

In a study comprised of data from seven different longitudinal studies including >11,000 participants who had risk factors assessed in adolescence and were then followed into adulthood, 4.4 percent experienced at least one ASCVD event by a mean age of 50 years [38]. ASCVD events included fatal or nonfatal myocardial infarction, stroke, transient ischemic attack, ischemic heart failure, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, or coronary revascularization. In multivariable analysis, each of the following risk factors in adolescence was independently associated with experiencing an ASCVD event in adulthood:

●Elevated blood pressure (hazard ratio [HR] 1.25, 95% CI 1.03-1.52)

●Obesity (HR 2.19, 95% CI 1.62-2.98)

●Smoking (HR 1.63, 95% CI 1.37-1.95)

●Elevated total cholesterol (HR 1.79, 95% CI 1.39-2.31)

The likelihood of experiencing an ASCVD event increased with increasing number of risk factors, ranging from 2.5 percent among participants with no risk factors in adolescence to 7.7 percent among those with ≥3 adolescent risk factors [38].

Elevated total cholesterol and elevated LDL-C were both independent predictors of ASCVD events in this study, whereas the study did not detect a significant association between elevated TG levels and ASCVD events. The investigators evaluated multivariable risk prediction models with and without lipid measurements and found that including lipid levels in the model did not improve its accuracy. However, HDL levels were not routinely available in all cohorts, limiting the interpretation of this finding.

Another study that linked data from the United States National Health and Nutrition Examination Survey (NHANES) (1988 to 1994) with the National Death Index demonstrated that diabetes, obesity, and smoking during adolescence and young adulthood (12 to 39 years of age) were associated with an increased risk for death before 55 years of age after accounting for age, sex, and race/ethnicity [39]. Because there were relatively few deaths, it was not possible to determine whether these factors were associated with cause-specific mortality (eg, cardiovascular deaths).

PEDIATRIC ASCVD RISK FACTORS — 

Traditional ASCVD risk factors and other specific conditions in children and adolescents are associated with accelerated atherosclerosis and early ASCVD (table 1 and algorithm 1) [40,41].

Prenatal exposures — There is emerging evidence that prenatal factors impact offspring cardiovascular health in adulthood. These include [42-44]:

●Fetal growth restriction (see "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns", section on 'Impact on health status in adulthood')

●Gestational and pregestational diabetes mellitus (see "Infants of mothers with diabetes (IMD)", section on 'Long-term outcome')

●Prepregnancy and pregnancy-induced hypertension and pre-eclampsia (see "Gestational hypertension" and "Preeclampsia: Intrapartum and postpartum management and long-term prognosis", section on 'Long-term risks in offspring')

●Excessive weight gain during pregnancy (see "Gestational weight gain" and "Obesity in pregnancy: Complications and maternal management")

●Maternal hyperlipidemia

●Smoking before, during, and/or after pregnancy(see "Cigarette and tobacco products in pregnancy: Screening and impact on pregnancy and the neonate")

Traditional ASCVD risk factors — Traditional ASCVD risk factors include (table 1) (see "Overview of established risk factors for cardiovascular disease"):

●Dyslipidemia (see 'Dyslipidemia' below)

●Elevated body mass index (BMI) (see 'Obesity' below)

●Diabetes mellitus (DM) (see 'Diabetes mellitus' below)

●Hypertension (see 'Hypertension' below)

●Family history of premature ASCVD (see 'Family history of premature ASCVD' below)

●Smoking (see 'Nicotine exposure' below)

These ASCVD risk factors are common in the pediatric population. In studies using data from the United States National Health and Nutrition Examination Survey (NHANES), the reported prevalence of ASCVD risk factors in children and adolescents age 8 to 19 years were [45-48]:

●Dyslipidemia – 20 to 30 percent

●Prediabetes/DM – 15 percent

●High blood pressure (BP) in the hypertensive range – 8 to 14 percent

The data linking these risk factors in childhood to ASCVD events are described above (see 'Association between pediatric risk factors and adult ASCVD' above). In addition, longitudinal studies demonstrate a moderate correlation between childhood blood pressure, serum lipid levels, and BMI with analogous values measured in middle age [49]. Thus, children with ASCVD risk factors are more likely to be at-risk adults.

Dyslipidemia — Dyslipidemias are disorders of lipoprotein metabolism that result in at least one of the following abnormalities (table 2) [40]:

●High total cholesterol

●High low-density lipoprotein cholesterol (LDL-C)

●Low high-density lipoprotein cholesterol

●High triglycerides

The evaluation and management of children with abnormal lipid profiles are discussed separately. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis" and "Dyslipidemia in children and adolescents: Management".)

Obesity — Numerous studies have shown that higher BMI during childhood is associated with increased risk of ASCVD in adulthood. For example, a large prospective cohort study of >270,000 Danish children born from 1930 to 1976 demonstrated that childhood BMI was associated with risk of experiencing ischemic coronary events in adulthood (eg, angina pectoris, acute myocardial infarction, other ischemic heart disease) [50]. There was a positive linear association between increasing BMI at every age from 7 to 13 years and the number of events in adulthood, with stronger associations in males as compared with females. The effect of excess weight on the risk of an event rose with increasing age. Relatively small increases in weight in childhood were associated with increased ASCVD risk in adulthood.

Other studies have shown that children or adolescents who are overweight (defined as BMI ≥85th percentile) or obese (defined as BMI percentile >95th percentile), compared with healthy-weight children, are more likely to be hypertensive, have dyslipidemia, develop insulin resistance and type 2 DM, and develop ASCVD as they age [51,52]. The cardiovascular comorbidities and complications of obesity in childhood are discussed in greater detail separately. (See "Overview of the health consequences of obesity in children and adolescents", section on 'Cardiovascular'.)

Studies demonstrating associations between elevated BMI in childhood/adolescence and preclinical atherosclerosis and/or ASCVD events later in life are discussed above. (See 'Association between pediatric risk factors and adult ASCVD' above.)

Overweight children are also more likely to be inactive, have obstructive sleep apnea, and have increased left ventricular mass, all of which are associated with ASCVD in adults. (See "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Persistence of obesity' and "Overweight and obesity in adults: Health consequences".)

Diabetes mellitus — Insulin resistance, hyperinsulinemia, and elevated blood glucose are associated with ASCVD. In addition, children with DM compared with those without DM are at increased risk for other ASCVD risk factors, such as hypertension and dyslipidemia. (See "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus" and "Overview of established risk factors for cardiovascular disease", section on 'Diabetes mellitus'.)

●Type 1 DM – In adolescents with type 1 DM, accelerated atherosclerotic changes have been described at autopsy and in studies demonstrating preclinical markers of atherosclerosis (eg, increased CIMT), abnormal arterial stiffness, and impaired endothelial function [53]. There have also been reports of myocardial infarctions in young adults with type 1 DM.

●Type 2 DM – In adolescents with type 2 DM, cardiovascular abnormalities, such as increased left ventricular wall thickness and increased arterial stiffness, have been reported. Children with type 2 DM often have comorbid obesity and are at increased risk of developing metabolic syndrome (also referred to as syndrome X or insulin resistance syndrome), a condition of multiple ASCVD risk factors (ie, dyslipidemia, hypertension, type 2 DM, and obesity). (See 'Clustered ASCVD risk factors' below and "Metabolic syndrome (insulin resistance syndrome or syndrome X)".)

The management of types 1 and 2 DM, including screening and prevention of ASCVD, are discussed separately. (See "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Cardiovascular disease' and "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus", section on 'Other microvascular complications'.)

Hypertension — In adults, hypertension is a well-established risk factor for ASCVD. (See "Cardiovascular risks of hypertension".)

Studies demonstrating associations between hypertension in childhood/adolescence and preclinical atherosclerosis and/or ASCVD events later in life are discussed above. (See 'Association between pediatric risk factors and adult ASCVD' above.)

In addition, patients with elevated blood pressure in childhood are more likely to have hypertension in adulthood.

The evaluation and treatment of hypertension in children and adolescents are discussed separately. (See "Hypertension in children and adolescents: Definition and diagnosis" and "Hypertension in children and adolescents: Nonemergency treatment".)

Family history of premature ASCVD — Individuals with first-degree relatives (parent or sibling) who have experienced premature ASCVD are at increased risk of ASCVD. Premature ASCVD in this context is generally defined as myocardial infarction, treated angina, interventions for coronary artery disease, sudden cardiac death, or ischemic stroke before age 55 (males) or 65 (females). (See "Overview of established risk factors for cardiovascular disease", section on 'Family history'.)

In children, subclinical vascular abnormalities can be seen among offspring of individuals with premature ASCVD. Evidence of accelerated atherosclerosis (eg, lower brachial arterial reactivity and greater CIMT) is more commonly detected in adolescent offspring of individuals with premature myocardial infarction compared with controls without a family history of premature ASCVD [15]. However, the sensitivity of a positive family history for detection of ASCVD or dyslipidemia appears to be relatively low. Several studies have shown that a positive family history fails to detect 30 to 60 percent of children with dyslipidemia [54] and that the risk of dyslipidemia may be independent of a family history of ASCVD [55]. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis", section on 'Rationale for lipid screening'.)

Nevertheless, individuals with a family history positive for early ASCVD disease have twice the risk of ASCVD as those without, even after adjusting for conventional risk factors [56]. The impact of a positive family history upon ASCVD is more fully discussed separately. (See "Overview of established risk factors for cardiovascular disease", section on 'Family history' and "Coronary artery disease and myocardial infarction in young people", section on 'Family history'.)

Nicotine exposure — Smoke exposure, including secondhand cigarette smoke, increases the risk of ASCVD [57]. Because of its addictive nature, pediatric tobacco use increases the risk of persistent adult smoking. The risk of CVD due to smoke exposure is discussed separately. (See "Cardiovascular risk of smoking and benefits of smoking cessation" and "Secondhand smoke exposure: Effects in children", section on 'Atherogenesis'.)

There is also evidence that the use of electronic nicotine delivery systems also may increase the risk of hypertension and ASCVD [58]. (See "Vaping and e-cigarettes", section on 'Adverse health effects'.)

Clustered ASCVD risk factors — Risk factors for premature ASCVD often cluster together. For example, a child or adolescent may have high BMI, elevated BP, dyslipidemia, and type 2 DM. The risk of premature ASCVD rises as the number of risk factors increases [1,13,27,47].

In a NHANES study, the likelihood of having one or more additional ASCVD risk factors rose with increasing BMI (37 percent for adolescents with normal BMI, 49 percent for those with overweight BMI [≥85th percentile], and 61 percent for those with obesity [BMI >95th percentile]) [47]. Among adolescents with obesity, 8 percent had ≥3 additional ASCVD risk factors. These data highlight the high prevalence of ASCVD risk factors in adolescents in the United States, especially among individuals with obesity.

The association between elevated BMI and other ASCVD risk factors was described in a meta-analysis of 63 observational studies, including >49,000 children [59]. Compared with children with healthy weight, those with obesity had higher systolic BP (mean difference 7.5 mmHg), higher total cholesterol (mean difference 6 mg/dL [0.15 mmol/L]), higher triglyceride levels (mean difference 23 mg/dL [0.26 mmol/L]), and increased left ventricular size.

The constellation of ASCVD risk factors that includes type 2 DM, abdominal obesity, hyperglycemia, dyslipidemia, and hypertension is sometimes referred to as metabolic syndrome. In one study, children between the ages of 6 to 19 years who were identified as meeting criteria for metabolic syndrome had a >10-fold higher risk of ASCVD at 25-year follow-up compared with the general school-age population (odds ratio [OR] 14.6, 95% CI 4.8-45.3) [60]. They were also more likely to have metabolic syndrome in adulthood (OR 6.2, 95% CI 2.8-13.8).

The construct of metabolic syndrome in childhood is primarily used in research. It is not used in routine clinical care because there is no consensus on the pediatric definition and the relationship between childhood metabolic syndrome and ASCVD events is not well characterized [61]. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)", section on 'Children and adolescents'.)

Modifiable health behaviors — The following health behaviors, while not considered independent risk factors for ASCVD per se, are nevertheless important aspects of promoting a heart-healthy lifestyle. These behaviors often contribute to some of the risk factors discussed above (eg, obesity, type 2 diabetes, dyslipidemia, hypertension). (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children".)

Diet — For all children, health care providers should promoting a heart-healthy diet that is rich in vegetables, fruits, and whole grains; low in saturated fat; and devoid of trans fats (table 3). (See "Dietary recommendations for toddlers and preschool and school-age children".)

Physical activity — Studies involving children and adults have shown that engaging in daily moderate or vigorous physical activity and limiting sedentary behavior improve cardiovascular health and reduce the risk of ASCVD in adulthood. Age-based goals for daily physical activity for children are summarized in the table (table 4) and discussed in greater detail separately. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children", section on 'Physical activity' and "Prevention and management of childhood obesity in the primary care setting", section on 'Physical activity goals' and "Physical activity and strength training in children and adolescents: An overview", section on 'Benefits of regular physical activity'.)

Sleep habits — In adults, abnormal sleep duration (both too little and too much) and sleep disordered breathing (eg, obstructive sleep apnea) have been linked to increased risk of ASCVD. These associations are discussed elsewhere. (See "Insufficient sleep: Definition, epidemiology, and adverse outcomes", section on 'Cardiovascular morbidity' and "Obstructive sleep apnea and cardiovascular disease in adults".)

There are fewer data establishing a link between sleep problems in childhood and risk of premature ASCVD. Nevertheless, establishing healthy sleep habits (table 5A-B), including appropriate duration of sleep (figure 1), is generally considered part of a heart-healthy lifestyle. (See "Assessment of sleep disorders in children".)

Other conditions — In addition to the risk factors listed above, other conditions that are associated with accelerated atherosclerosis and premature ASCVD include the following (algorithm 1 and table 1) [40,41,62].

Familial hypercholesterolemia — Familial hypercholesterolemia (FH) is an autosomal codominant genetic disease. The clinical syndrome (phenotype) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) level from birth, xanthomata in untreated adults and patients with homozygous FH, and a propensity to early-onset ASCVD.

The diagnosis and treatment of FH are discussed separately. (See "Familial hypercholesterolemia in children" and "Familial hypercholesterolemia in children", section on 'Management'.)

Children with other monogenetic defects or with a high abundance of polygenic contributions can have a phenotype similar to FH. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

Chronic kidney disease

●Nephrotic syndrome – Individuals with childhood-onset nephrotic syndrome are at increased risk for early atherosclerosis in part due to hyperlipidemia, which is a characteristic feature of nephrotic syndrome. Other factors that may play a role include chronic inflammation, hypercoagulability, and the effects of corticosteroid therapy. Studies have demonstrated evidence of preclinical atherosclerosis (increased CIMT, abnormal FMD]) in patients with childhood-onset nephrotic syndrome [63-65]. Complications of pediatric nephrotic syndrome and clinical implications of lipid abnormalities in nephrotic syndrome are discussed separately. (See "Complications of nephrotic syndrome in children" and "Lipid abnormalities in nephrotic syndrome", section on 'Clinical implications'.)

●Other types of chronic kidney disease (CKD) – Children with CKD are at increased risk for developing ASCVD. Accelerated atherosclerosis has been demonstrated in iliac artery samples at the time of kidney transplantation and at autopsy [66,67].Children with CKD often have additional ASCVD risk factors, including hypertension and dyslipidemia. Studies have demonstrated evidence of preclinical atherosclerosis (eg, coronary artery calcification, abnormal flow-mediated dilation [FMD], increased carotid intima-medial thickness [CIMT], increased aortic stiffness) and left ventricular hypertrophy in pediatric patients with CKD [67-72]. These abnormalities seem to be, in part, related to the degree of uremia. In addition, some medications used to prevent kidney transplant rejection are associated with ASCVD risk factors (eg, cyclosporine is associated with hypertension; rapamycin is associated with dyslipidemia; corticosteroids are associated with hypertriglyceridemia, hypertension, and diabetes mellitus [DM]). (See "Chronic kidney disease in children: Complications", section on 'Risk for cardiovascular disease'.)

Kawasaki disease — Kawasaki disease (KD; also called mucocutaneous lymph node syndrome) is one of the most common vasculitides of childhood and is associated with the development of coronary artery aneurysms, which can lead to myocardial ischemia or infarction (movie 1 and movie 2). In resource-abundant countries, KD has surpassed rheumatic fever as the leading cause of acquired cardiovascular disease in childhood.

The risk of ASCVD in patients with a history of KD depends upon initial aneurysm size, occurrence of coronary thrombosis, and degree and nature of remodeling of the arterial wall over time. This is discussed in detail separately. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Atherosclerotic coronary artery disease'.)

Coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children (MIS-C) can cause a clinical illness similar to that of KD. Coronary involvement can occur in MIS-C, though it is less common than in KD. It is unclear if children who have recovered from MIS-C are at increased risk for premature ASCVD since long-term follow-up data are not available. Follow-up in patients with MIS-C is discussed separately. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Follow-up'.)

Childhood cancer — As life expectancy for pediatric cancer survivors has improved, it has become increasingly apparent that these patients are at risk for premature ASCVD [73-75]. The increased risk in this population is likely due to a combination of damaged myocardium and direct vascular effect from chemotherapeutic agents, particularly anthracyclines [76]. Radiation therapy, particularly to the mediastinum, is also associated with premature atherosclerosis [77]. In addition, survivors of childhood cancer are more likely to have other ASCVD risk factors including obesity, insulin resistance, and dyslipidemia [78-83]. Issues related to cancer survivorship are discussed in greater detail separately. (See "Cancer survivorship: Cardiovascular and respiratory issues" and "Overview of cancer survivorship in adolescents and young adults".)

Cardiac transplant vasculopathy — In children who undergo cardiac transplantation, transplant vasculopathy is a significant long-term complication and cause of death [84]. A multicenter autopsy study demonstrated severe coronary stenosis in 28 of 36 children deceased after cardiac transplant [84]. Approximately three-quarters of children with cardiac transplantation have evidence of coronary artery abnormalities detected by angiography and intracoronary ultrasonography [85,86].

Cardiac transplant vasculopathy leads to the development of vessel narrowing secondary to thickening of the intimal and medial layers of the coronary. It appears to be multifactorial in origin, with both immunologic and nonimmunologic factors being implicated. Among the factors associated with vasculopathy are cellular and vascular rejection, anti-human leukocyte antigen antibody production, and cytomegalovirus infection. Patients with cardiac transplants are likely to have other ASCVD risk factors, such as dyslipidemia, hypertension, elevated body mass index (BMI), DM, and deconditioning. Similar to children who undergo kidney transplantation, these additional risk factors may be associated with medications used to prevent rejection. (See "Heart transplantation in adults: Cardiac allograft vasculopathy risk factors, surveillance, and diagnosis".)

The management of patients with cardiac transplantation to prevent and treat cardiac transplant vasculopathy, as well as to screen and treat dyslipidemia, is discussed separately. (See "Heart transplantation: Prevention and treatment of cardiac allograft vasculopathy" and "Heart transplantation: Hyperlipidemia after transplantation".)

Congenital heart disease — Congenital heart disease (CHD) occurs in approximately 1 percent of live births. Because of improvements in surgical, transcatheter, and perioperative management, many more children with CHD are surviving to adulthood in the contemporary era compared with previous eras. As a result, there is increasing evidence that some CHD defects are associated with an increased risk for premature ASCVD.

Risk of ASCVD is likely to be greatest in those with coronary artery abnormalities or left-sided obstructive lesions.

●Coronary artery abnormalities – In patients with coronary artery anomalies, premature atherosclerosis of the coronary artery has been demonstrated in autopsies [87] and detected by coronary artery angiography [88]. In addition, surgical manipulation of the coronary arteries, especially associated with the arterial switch operation for transposition of the great arteries, is associated with increased risk for coronary artery stenosis, premature atherosclerosis, and coronary artery dysfunction [89-91]. (See "D-transposition of the great arteries (D-TGA): Management and outcome", section on 'Early atherosclerotic coronary artery disease'.)

●Left-sided obstructive lesions – Cardiac lesions that obstruct the left ventricle or aorta, such as aortic stenosis and coarctation, are associated with an increased risk of ASCVD in adulthood. In children with coarctation of the aorta, the aorta is less compliant and reactive and the CIMT and femoral IMT is increased [92]. Hypertension is common in patients with coarctation, even years after apparently successful repair. (See "Valvar aortic stenosis in children" and "Clinical manifestations and diagnosis of coarctation of the aorta".)

●Comorbid obesity – Children with CHD are not immune to the obesity epidemic. Observational data suggest the prevalence of overweight and obesity in children with CHD is similar to that of the general population [93,94]. However, the physiologic consequences of obesity may be greater in the CHD population.

Chronic inflammatory diseases — It is well established that the prevalence of ASCVD is increased in adults with chronic inflammatory illnesses, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Increasing evidence suggests that children and adolescents affected by these disorders often have increased ASCVD risk factors [62], with nearly three-quarters reported to have accelerated atherosclerosis associated with dyslipidemia, and a higher risk of premature ASCVD [95]. Children and adolescents with SLE have increased CIMT compared with healthy controls [96]. (See "Childhood-onset systemic lupus erythematosus (cSLE): Clinical manifestations and diagnosis", section on 'Cardiac and vascular' and "Systemic lupus erythematosus in adults: Coronary artery disease".)

HIV infection — Considerable progress has been made in the treatment and prevention of pediatric HIV infection, and life expectancy for HIV-infected children has improved considerably in the era of potent antiretroviral therapy. However, in children infected with HIV early in life, prolonged exposure to HIV and antiretroviral therapy is associated with a number of long-term complications, including dyslipidemia, DM, lipodystrophy, and hypertension [97]. For instance, patients with perinatally acquired HIV infection have been found to have indirect evidence of subclinical coronary vascular disease (ie, increased coronary artery wall thickness) [98,99]. ASCVD risk in youth with perinatal HIV infection is likely multifactorial. In addition to traditional ASCVD risk factors, chronic inflammation, abnormal immune function, side effects of antiretroviral therapy, and direct HIV viral effects may contribute. Long-term morbidities in HIV-infected children are discussed in greater detail separately. (See "Pediatric HIV infection: Epidemiology, clinical manifestations, and outcome", section on 'Long-term morbidities'.)

Depressive and bipolar disorders — Growing evidence suggests that major depressive disorder and bipolar disorder in adolescence may be associated with premature ASCVD. The mechanism appears to be multifactorial and multiple systemic processes have been implicated, including inflammation, oxidative stress, and autonomic dysfunction [100]. The association between depressive and bipolar disorders, particularly major depression, and ASCVD in adults is well established. (See "Psychosocial factors in acute coronary syndrome", section on 'Depression' and "Psychosocial factors in coronary and cerebral vascular disease".)

Depressive and bipolar disorders that begin in childhood or adolescence can persist into adulthood. In addition, many traditional ASCVD risk factors (eg, DM, obesity, sedentary lifestyle, smoking) are more prevalent among adolescents with major depressive disorder and bipolar disorder compared with the general pediatric population [100]. In observational studies of adolescents and young adults, the relationship between major depressive disorder and bipolar disorder and indirect measures of atherosclerosis (ie, CIMT, ultrasound-determined brachial artery flow-mediated dilation, or digital pulse-wave amplitude) is inconsistent [100]. (See "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis" and "Pediatric bipolar disorder: Clinical manifestations and course of illness".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lipid disorders and atherosclerosis in children".)

SUMMARY AND RECOMMENDATIONS

●Atherosclerotic changes in childhood – Although atherosclerotic cardiovascular disease (ASCVD) generally manifests clinically in adulthood, there is substantial evidence that atherosclerosis can begin in childhood. A childhood origin of ASCVD is supported by direct evidence from autopsy studies, indirect data showing subclinical vascular changes, and longitudinal studies linking ASCVD risk factors in childhood/adolescence to development of clinical ASCVD in adulthood. (See 'Association between pediatric risk factors and adult ASCVD' above.)

●Traditional risk factors – Traditional ASCVD risk factors include (table 1) (see 'Traditional ASCVD risk factors' above):

•Dyslipidemia (see 'Dyslipidemia' above and "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis")

•Overweight/obesity (see 'Obesity' above and "Definition, epidemiology, and etiology of obesity in children and adolescents")

•Diabetes mellitus (DM; type 1 or 2) (see 'Diabetes mellitus' above)

•Hypertension (see 'Hypertension' above and "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology")

•Family history of premature ASCVD (see 'Family history of premature ASCVD' above)

•Smoking/nicotine exposure (see 'Nicotine exposure' above and "Secondhand smoke exposure: Effects in children" and "Prevention of smoking and vaping initiation in children and adolescents")

●Other conditions – Other conditions associated with increased risk of premature CVD include (table 1) (see 'Other conditions' above):

•Familial hypercholesterolemia (FH) (see 'Familial hypercholesterolemia' above and "Familial hypercholesterolemia in children")

•Chronic kidney disease (CKD) (see 'Chronic kidney disease' above and "Chronic kidney disease in children: Complications", section on 'Risk for cardiovascular disease')

•Kawasaki disease (see 'Kawasaki disease' above and "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation", section on 'Atherosclerotic coronary artery disease')

•Childhood cancer (See 'Childhood cancer' above and "Cancer survivorship: Cardiovascular and respiratory issues".)

•Cardiac transplant vasculopathy (see 'Cardiac transplant vasculopathy' above)

•Certain congenital heart disease (CHD) defects and cardiomyopathies (see 'Congenital heart disease' above)

•Chronic inflammatory disease (eg, systemic lupus erythematosus [SLE]) (see 'Chronic inflammatory diseases' above and "Systemic lupus erythematosus in adults: Coronary artery disease")

•HIV (see 'HIV infection' above and "Pediatric HIV infection: Epidemiology, clinical manifestations, and outcome", section on 'Long-term morbidities')

•Adolescent mood disorders (see 'Depressive and bipolar disorders' above and "Psychosocial factors in coronary and cerebral vascular disease")

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Jane Newburger, MD, MPH, and Michael Mendelson, MD, ScM, who contributed to an earlier version of this topic review.

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Topic 5781 Version 49.0

References

1 : Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study.

2 : 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.

3 : Determinants of atherosclerosis in the young. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

4 : Pathobiological determinants of atherosclerosis in youth risk scores are associated with early and advanced atherosclerosis.

5 : Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study.

6 : Prevalence of and risk factors for autopsy-determined atherosclerosis among US service members, 2001-2011.

7 : Pediatric precursors of adult cardiovascular disease: noninvasive assessment of early vascular changes in children and adolescents.

8 : Noninvasive assessment of arterial stiffness and risk of atherosclerotic events in children.

9 : Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study.

10 : Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study.

11 : Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study.

12 : Risk factors associated with aortic and carotid intima-media thickness in adolescents and young adults: the Muscatine Offspring Study.

13 : 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.

14 : Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children.

15 : Arterial abnormalities in the offspring of patients with premature myocardial infarction.

16 : Carotid intima-media thickness in children with familial hypercholesterolemia.

17 : Arterial wall thickening and stiffening in children and adolescents with type 1 diabetes.

18 : Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function.

19 : Non-HDL Cholesterol Levels in Childhood and Carotid Intima-Media Thickness in Adulthood.

20 : 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.

21 : Impact of Lipid Measurements in Youth in Addition to Conventional Clinic-Based Risk Factors on Predicting Preclinical Atherosclerosis in Adulthood: International Childhood Cardiovascular Cohort Consortium.

22 : Assessment of vascular function: pulse wave velocity.

23 : Association between brachial-ankle pulse wave velocity and cardiovascular risk factors in healthy adolescents.

24 : Childhood blood pressure as a predictor of arterial stiffness in young adults: the bogalusa heart study.

25 : Relationship between elevated arterial stiffness and increased left ventricular mass in adolescents and young adults.

26 : Increased arterial stiffness is found in adolescents with obesity or obesity-related type 2 diabetes mellitus.

27 : Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study.

28 : Conventional cardiovascular risk factors and metabolic syndrome in predicting carotid intima-media thickness progression in young adults: the cardiovascular risk in young Finns study.

29 : Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study.

30 : Elevated blood pressure in adolescent boys predicts endothelial dysfunction: the cardiovascular risk in young Finns study.

31 : Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study.

32 : Life-course risk factor levels and coronary artery calcification. The Cardiovascular Risk in Young Finns Study.

33 : Risk Factor Profile in Youth, Genetic Risk, and Adulthood Cognitive Function: The Cardiovascular Risk in Young Finns Study.

34 : Cardiovascular Risk Factors From Childhood and Midlife Cognitive Performance: The Young Finns Study.

35 : Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study.

36 : Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study.

37 : Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

38 : Predictors in Youth of Adult Cardiovascular Events.

39 : Cardiometabolic risk factors among US adolescents and young adults and risk of early mortality.

40 : Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report.

41 : Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement From the American Heart Association.

42 : Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study.

43 : Maternal obesity during pregnancy and cardiovascular development and disease in the offspring.

44 : Maternal Hypertension During Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis.

45 : Hypertension Among Youths - United States, 2001-2016.

46 : Prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999-2012.

47 : Prevalence of cardiovascular disease risk factors among US adolescents, 1999-2008.

48 : Trends in Levels of Lipids and Apolipoprotein B in US Youths Aged 6 to 19 Years, 1999-2016.

49 : Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study.

50 : Childhood body-mass index and the risk of coronary heart disease in adulthood.

51 : Childhood Body Weight in Relation to Cause-Specific Mortality: 67 Year Follow-up of Participants in the 1947 Scottish Mental Survey.

52 : Cardiometabolic Risks and Severity of Obesity in Children and Young Adults.

53 : Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes.

54 : Screening and treatment for lipid disorders in children and adolescents: systematic evidence review for the US Preventive Services Task Force.

55 : Universal versus targeted blood cholesterol screening among youth: The CARDIAC project.

56 : Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.

57 : Cardiovascular Consequences of Childhood Secondhand Tobacco Smoke Exposure: Prevailing Evidence, Burden, and Racial and Socioeconomic Disparities: A Scientific Statement From the American Heart Association.

58 : 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

59 : Cardiovascular disease risk in healthy children and its association with body mass index: systematic review and meta-analysis.

60 : Metabolic syndrome in childhood predicts adult cardiovascular disease 25 years later: the Princeton Lipid Research Clinics Follow-up Study.

61 : 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.

62 : 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.

63 : Carotid intima-media thickness in children with idiopathic nephrotic syndrome: A single center cross-sectional study
.

64 : Long-term complications in patients with childhood-onset nephrotic syndrome.

65 : Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control study.

66 : Arterial changes in paediatric haemodialysis patients undergoing renal transplantation.

67 : Patient survival and causes of death on hemodialysis and peritoneal dialysis--single-center study.

68 : Left ventricular mass and systolic performance in pediatric patients with chronic renal failure.

69 : Doppler assessment of brachial artery flow as a measure of endothelial dysfunction in pediatric chronic renal failure.

70 : Evolution of large-vessel arteriopathy in paediatric patients with chronic kidney disease.

71 : Increased arterial stiffness in children on haemodialysis.

72 : Evaluation of aortic stiffness in children with chronic renal failure.

73 : Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort.

74 : Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study.

75 : Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population-based cohort study of 32,308 one-year survivors.

76 : Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention.

77 : Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group.

78 : Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors.

79 : Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence.

80 : Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

81 : Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood.

82 : Cardiovascular status, subsequent risk, and associated factors in long-term survivors of childhood cancer in a population-based study

83 : Cardiovascular risk and insulin resistance in childhood cancer survivors.

84 : Posttransplant coronary artery disease in children. A multicenter national survey.

85 : Transplant coronary artery disease in pediatric heart transplant recipients.

86 : The medium-term findings in coronary arteries by intravascular ultrasound in infants and children after heart transplantation.

87 : Major anomalies of coronary arterial origin seen in adulthood.

88 : Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival--a report from the Coronary Artery Surgery Study.

89 : Detection of coronary complications after the arterial switch operation for transposition of the great arteries: first experience with multislice computed tomography in children.

90 : Intracoronary ultrasound assessment late after the arterial switch operation for transposition of the great arteries.

91 : 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.

92 : Increased carotid and femoral intima-media thickness in patients after repair of aortic coarctation: influence of early repair.

93 : Obesity is a common comorbidity in children with congenital and acquired heart disease.

94 : Risk factors and comorbidities associated with obesity in children and adolescents after the arterial switch operation and Ross procedure.

95 : Effects of dietary modification and fish oil supplementation on dyslipoproteinemia in pediatric systemic lupus erythematosus.

96 : Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.

97 : Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

98 : Increased coronary vessel wall thickness in HIV-infected young adults.

99 : Effects of paediatric HIV infection on childhood vasculature.

100 : Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.