INTRODUCTION — While cardiovascular disease (CVD) events primarily occur in adulthood, the atherosclerotic process may begin in childhood. For most children, vascular changes, if present, are mild and can be minimized with adherence to a healthy lifestyle. However, in some children, the atherosclerotic process is accelerated because of the presence of identifiable risk factors (table 1) [1]. Identification of children and adolescents at risk for accelerated atherosclerosis allows for timely interventions targeted at modifiable risk factors to slow the atherosclerotic process and thereby potentially prevent or delay CVD [1-3].
An overview of the management of the child or adolescent at risk for atherosclerosis will be presented here. Primary prevention of atherosclerosis in children, identifying the child at risk for atherosclerosis, and the risk factors for pediatric atherosclerosis are discussed separately. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children" and "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
RATIONALE FOR INTERVENTION — Large, prospective, population-based, randomized controlled trial studies in adults demonstrate that reducing risk factors associated with cardiovascular disease (CVD) decreases the occurrence of future CVD events. (See "Overview of established risk factors for cardiovascular disease", section on 'Established risk factors for atherosclerotic CVD'.)
Similar long-term outcome data based on randomized clinical trials are not available for the pediatric population. Prospective observational studies link the development of early-onset CVD risk factors to premature atherosclerotic changes in children. Furthermore, CVD risk factors track from childhood to adulthood. Short-term randomized controlled trials in children have demonstrated that lifestyle and pharmacotherapy interventions can successfully reduce CVD risk factors in high-risk pediatric populations. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Atherosclerotic changes in childhood'.)
As a result, it is reasonable to assume, based on the evidence from adult studies and limited pediatric data, that timely interventions to decrease or eliminate CVD risk factors in children can potentially slow the atherosclerotic process and thereby prevent or delay the onset of CVD [2-5].
CARDIOVASCULAR DISEASE RISK FACTORS
Modifiable risk factors — Modifiable cardiovascular disease (CVD) risk factors that may present during childhood and adolescence include the following (table 1) [4,5]:
●Dyslipidemia (see 'Dyslipidemia' below)
●Hypertension (HTN) (see 'Hypertension' below)
●Insulin resistance and diabetes mellitus (see 'Insulin resistance and diabetes mellitus' below)
●Obesity (see 'Obesity' below)
●Smoking cigarettes and other nicotine exposures (see 'Smoking and nicotine exposure' below)
●Physical inactivity (see 'Activity and inactivity' below)
In addition, concomitant conditions contributing to a higher risk of atherosclerosis and CVD should be considered when deciding whether to initiate therapeutic interventions aimed at reducing CVD risk. (See 'Other conditions' below and "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
Other conditions — In addition to the conditions listed above, other specific conditions are associated with accelerated atherosclerosis and premature CVD. These conditions are summarized in the table and are discussed in greater detail separately (table 1) [4,5] (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Other conditions'.):
For children with one of these conditions, heightened awareness and evaluation for concurrent CVD risk factors are warranted. Similar to adults, in whom multiple risk factors are considered in the evaluation of risk for CVD, each of the additional risk factors described below are considered when making treatment decisions (algorithm 1).
Management of these patients should include treatment of both the underlying primary disease and any comorbid CVD risk factors. The decision to initiate treatment and the nature of intervention are dependent upon the assessment of the degree of CVD risk for the individual child, based upon his/her underlying disease and the presence of comorbid conditions such as HTN, dyslipidemia, and obesity. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
DYSLIPIDEMIA — Dyslipidemias are disorders of lipoprotein metabolism defined by abnormalities in the lipid (table 2) [5]. The rationale for initiating therapy to control lipid disorders in children and adolescents is based upon increasing evidence that pediatric dyslipidemia (particularly elevated low-density lipoprotein cholesterol) contributes to premature atherosclerosis and the early development of cardiovascular disease (CVD).
Lipid screening in children and the management of pediatric dyslipidemias are discussed in detail separately. (See "Dyslipidemia in children and adolescents: Definition, screening, and diagnosis" and "Dyslipidemia in children and adolescents: Management".)
HYPERTENSION — Hypertension (HTN) in children is defined based on the normative distribution of blood pressure (BP) in healthy children (table 3 and table 4 and table 5). The diagnosis of HTN is based on repeated multiple BP measurements separated over time. (See "Definition and diagnosis of hypertension in children and adolescents".)
Treatment for HTN includes both nonpharmacologic and pharmacologic interventions. Management decisions are dependent upon the severity of HTN, underlying cause, evidence of end-organ damage, and presence of other cardiovascular disease (CVD) risk factors [6].
Although there is no direct evidence that initiating therapy to lower BP in children and adolescents with persistent HTN lowers the risk of subsequent CVD [6,7], there are indirect data that HTN in childhood and adolescence contributes to premature atherosclerosis and early development of CVD [8-10]. These data suggest that lowering the BP in hypertensive children would reduce the risk of accelerated atherosclerosis and, subsequently, premature CVD in adults.
The treatment of HTN in children and adolescents is discussed in greater detail separately. (See "Nonemergent treatment of hypertension in children and adolescents".)
INSULIN RESISTANCE AND DIABETES MELLITUS — Insulin resistance, hyperinsulinemia, and elevated blood glucose are associated with atherosclerotic cardiovascular disease (CVD). In addition, children with diabetes mellitus are at increased risk for other atherogenic risk factors such as hypertension (HTN) and dyslipidemia.
Randomized trials in adults and adolescents with type 1 diabetes mellitus have established that poor glycemic control contributes to long-term vascular sequelae. In addition, adult and adolescent clinical trials demonstrate that intensive insulin therapy, resulting in hemoglobin A1c levels <7, decreases the incidence of CVD. As a result, intensive glycemic control is recommended for children and adolescents with type 1 diabetes with age-specific goals for hemoglobin A1c levels. Similar recommendations are made for children with type 2 diabetes mellitus, particularly as these children are more commonly overweight, and some believe their CVD risk may be higher. (See "Overview of the management of type 1 diabetes mellitus in children and adolescents" and "Complications and screening in children and adolescents with type 1 diabetes mellitus" and "Management of type 2 diabetes mellitus in children and adolescents".)
Children with type 1 or type 2 diabetes should undergo screening for dyslipidemia and should be evaluated for HTN at each medical encounter [5,6,11]. It should be noted that most clinical guidance recommends using lower thresholds for initiating lipid-lowering therapy for patients with type 1 or type 2 diabetes. (See "Complications and screening in children and adolescents with type 1 diabetes mellitus" and "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus".)
OBESITY — Obesity, particularly central adiposity, is associated with accelerated atherosclerosis in childhood and increased risk of cardiovascular disease (CVD) in adulthood. Treatment for obesity in childhood is difficult and involves lifestyle changes at many levels. A multidisciplinary approach is encouraged, involving nutritional modification, behavioral counseling, and increased physical activity. The targeted body mass index is ideally less than the 85th percentile for age and gender. These issues are addressed in separate topic reviews. (See "Prevention and management of childhood obesity in the primary care setting" and "Clinical evaluation of the child or adolescent with obesity" and "Overview of the health consequences of obesity in children and adolescents".)
SMOKING AND NICOTINE EXPOSURE — Because smoke exposure, including secondhand smoke, increases the risk of cardiovascular disease (CVD), all patients and their close contacts who smoke should be counseled to quit smoking on a regular basis. A number of approaches, including behavioral therapy, nicotine replacement therapy, and other pharmacologic therapies, are available. (See "Management of smoking and vaping cessation in adolescents" and "Behavioral approaches to smoking cessation" and "Secondhand smoke exposure: Effects in children" and "Control of secondhand smoke exposure", section on 'Pediatrics' and "Overview of smoking cessation management in adults".)
ACTIVITY AND INACTIVITY — Evidence from both adult and pediatric studies demonstrates that daily vigorous activity and reduction in sedentary behavior improves cardiovascular disease (CVD) risk factors and decreases the occurrence of CVD events. The American Academy of Pediatrics and the National Heart, Lung, and Blood Institute expert panels recommend age-based daily activity for all children (table 6) [5]. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children", section on 'Physical activity'.)
In a child who has been inactive, we generally start at a lower intensity and frequency, moving to the ultimate goal of at least 60 minutes of moderate to vigorous physical activity for at least five days a week. The exercise regimen is increased gradually week by week to avoid setting unattainable goals. Directions on the expected exercise goals should be specific and clear to both the patient and family.
We also suggest limiting inactivity in the form of screen time (eg, computer, video games, television) to ≤2 hours per day.
Physical activity and cardiovascular health in children and adults are discussed separately. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children", section on 'Physical activity' and "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease".)
APPROACH TO THERAPY — The medical judgment of care providers, the clinical setting, and the preference of patients and their families inform decision-making. Ideally, the decision to initiate therapy to reduce the risk of cardiovascular disease (CVD) should be based upon an estimate of the absolute risk reduction and the potential risk of significant side effects of the therapeutic intervention. Although data are available to estimate the risk-benefit of intervention for individual adults, similar data for children are not available. Thus, treatment decisions are based on estimates of benefits and risks that are imprecise at best. In particular, the decision to intervene in children with multiple risk factors is challenging because evidence is often indirect and the desire to limit the use of medications must be balanced against the benefits of global risk factor reduction. In addition, the thresholds for initiation of pharmacologic management of one risk factor may vary depending upon the severity of other risk factors. For example, a child with dyslipidemia associated with type 1 diabetes may require more stringent lipid management than a child without diabetes. In some cases, intervention is warranted regardless of comorbidities, such as in children with very high low-density lipid levels suggestive of familial hypercholesterolemia or individuals with severe hypertension (HTN). Shared decision-making is encouraged. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood" and "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach".)
Our management approach is as follows and is consistent with published guidelines (algorithm 1) [5,6]. Therapy includes nonpharmacologic and pharmacologic interventions.
●Counseling for weight reduction in overweight/obese patients including dietary factors and increased physical activity. (See 'Obesity' above.)
●Promoting a healthy diet rich in vegetables, fruits, and whole grains; low in saturated fat; and devoid of trans fats (table 7).
●Counseling to foster increased activity to an ultimate goal of at least 60 minutes of moderate to vigorous physical activity for most days of the week and limiting screen time (eg, computer and television) to less than two hours a day (table 6). (See 'Activity and inactivity' above.)
●Counseling for smoking cessation for patients or family members who smoke, prevention of secondhand smoke exposure, and avoidance of initiation of nicotine use. (See "Management of smoking and vaping cessation in adolescents" and "Behavioral approaches to smoking cessation" and "Control of secondhand smoke exposure", section on 'Pediatrics'.)
●In patients with an underlying disease associated with an increased risk of CVD, treatment of the primary disease. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
●Management of modifiable risk factors such as dyslipidemia, HTN, and diabetes, as discussed in the above sections and separate topic reviews, with the strength of the intervention based upon the severity of the child's condition and existence of other comorbid conditions. (See "Dyslipidemia in children and adolescents: Management" and "Nonemergent treatment of hypertension in children and adolescents" and "Overview of the management of type 1 diabetes mellitus in children and adolescents" and "Management of type 2 diabetes mellitus in children and adolescents".)
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
●The rationale to treat children who are at risk for atherosclerosis, delaying the onset of the atherosclerotic process and, by extension, cardiovascular disease (CVD), is based on evidence from large adult population studies and more limited pediatric data that demonstrate an association between premature atherosclerosis and modifiable cardiovascular risk factors. These risk factors include dyslipidemia, hypertension (HTN), overweight or obesity, insulin resistance and diabetes mellitus, and smoke exposure (table 1). (See 'Rationale for intervention' above and "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
●The decision of whether to initiate therapy for an individual child at risk for atherosclerosis is based upon an estimate of the global risk for that child and the potential risk of significant side effects of the therapeutic intervention. Therapy includes nonpharmacologic and pharmacologic interventions. The initiation and aggressiveness of the therapy are generally based upon the number of CVD risk factors and their severity (ie, dyslipidemia, HTN, and overweight) as well as the preference of patients and their families. (See 'Approach to therapy' above.)
●Our management approach includes all of the following components (algorithm 1):
•Counseling for weight reduction in obese patients including dietary intervention and increased physical activity. (See 'Obesity' above.)
•Promoting a healthy diet rich in vegetables, fruits, and whole grains; low in saturated fat; and devoid of trans fats (table 7).
•Counseling to foster increased activity to an ultimate goal of at least 60 minutes of moderate to vigorous physical activity for most days of the week and limiting screen time (eg, computer and television) to less than two hours a day. (See 'Activity and inactivity' above.)
•Counseling for smoking cessation for patients or family members who smoke, prevention of secondhand smoke exposure, and avoidance of initiation of nicotine use. (See "Management of smoking and vaping cessation in adolescents" and "Behavioral approaches to smoking cessation" and "Control of secondhand smoke exposure", section on 'Pediatrics'.)
•In patients with an underlying disease associated with an increased risk of CVD, treatment of the primary disease (table 1). (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood".)
•Management of modifiable risk factors such as dyslipidemia, HTN, and diabetes, with the strength of the intervention based upon the severity of the child's condition and existence of other comorbid conditions. (See "Dyslipidemia in children and adolescents: Management" and "Nonemergent treatment of hypertension in children and adolescents".)
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.
