Dyslipidemia in children and adolescents: Definition, screening, and diagnosis

INTRODUCTION — 

Dyslipidemias are disorders of lipoprotein metabolism that result in the following abnormalities:

●High total cholesterol (TC)

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

●High non-high-density lipoprotein cholesterol (non-HDL-C)

●High triglycerides

●Low HDL-C

In adults, dyslipidemia is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), and correcting dyslipidemia reduces the risk of ASCVD. Dyslipidemia often begins in childhood and adolescence. Identifying children with dyslipidemia and successfully improving their lipid profile may reduce their risk of accelerated atherosclerosis and premature ASCVD.

The definition of pediatric dyslipidemia and the approach to screening, evaluation, and diagnosis of lipid disorders in children will be reviewed here. Management of pediatric dyslipidemia is discussed separately. (See "Dyslipidemia in children and adolescents: Management".)

Other related topics include:

●(See "Familial hypercholesterolemia in children".)

●(See "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)".)

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

●(See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia".)

●(See "Screening for lipid disorders in adults".)

DEFINITION

Normative values — Normal lipid and lipoprotein values in children vary by age and sex (table 1) [1,2]. Normative values are derived from population-based data from the Lipid Research Clinical Prevalence Study, which obtained fasting lipoprotein profiles from 15,626 children (age range 0 to 19 years) between 1972 and 1976 [3], and from the United States National Health and Nutrition Examination Surveys (NHANES), which collected lipid levels in 7000 children from 1988 to 1994 [4-7].

Lipid levels change with normal growth and maturation. Lipoproteins are very low in cord blood at birth and rise slowly in the first two years of life. Higher cholesterol levels are seen in breastfed babies related to the higher saturated fat content of breast milk [8]. Lipid levels are relatively stable from two years of age until adolescence. During puberty, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels decrease with increasing age, before rising in the late teenage years. Males experience a decrease in high-density lipoprotein (HDL) levels during late puberty, whereas HDL levels remain stable in females until menopause.

Definition of pediatric dyslipidemia — Based on the above normative data, cutoff points are used to delineate lipid values as "acceptable," "borderline," and "abnormal," as shown in the table (table 2). Dyslipidemia is defined as one or more abnormal lipid level:

●TC ≥200 mg/dL (5.2 mmol/L)

●LDL-C ≥130 mg/dL (3.4 mmol/L)

●Non-high-density lipoprotein cholesterol (non-HDL-C) ≥145 mg/dL (3.8 mmol/L)

●HDL-C <40 mg/dL (1.0 mmol/L)

●Triglycerides ≥100 mg/dL (1.1 mmol/L) in children <10 years and ≥130 mg/dL (1.5 mmol/L) in children >10 years

These definitions are consistent with guidelines of the National Heart, Lung, and Blood Institute, the American Academy of Pediatrics, and the American Heart Association/American College of Cardiology [1,9-11]. However, it should be noted that these cutoff points have not been validated as accurate predictors for accelerated atherosclerosis or atherosclerotic cardiovascular disease (ASCVD) events.

Lipoprotein(a) and apolipoproteins A and B levels are generally not included in the definition of pediatric dyslipidemia, though they play a role in the pathogenesis of atherosclerosis. This is discussed separately. (See "Lipoprotein(a)" and "Lipoprotein classification, metabolism, and role in atherosclerosis".)

PREVALENCE — 

In the United States, approximately 20 percent of children (age 6 to 19 years) have adverse levels of one or more lipid value [2,12-14]. The prevalence of adverse lipid levels increases with age, with 15 percent of children aged 6 to 11 years and 25 percent of adolescents aged 12 to 19 years having at least one adverse level [14].

The prevalence of specific abnormalities are as follows (note that a child may have more than one abnormality) [14]:

●Elevated total cholesterol (TC; ≥200 mg/dL [5.2 mmol/L]) – 7.1 percent

●Elevated low-density lipoprotein cholesterol (LDL-C; ≥130 mg/dL [3.4 mmol/L]) – 6.4 percent

●Elevated non-high-density lipoprotein cholesterol (non-HDL-C) levels (≥145 mg/dL [3.8 mmol/L]) – 6.4 percent

●Elevated triglyceride (≥130 mg/dL [1.5 mmol/L]) – 10.2 percent

●Low HDL-C (<40 mg/dL [1.0 mmol/L]) – 12.1 percent

Lipid levels are impacted by obesity. In an analysis of the United States National Health and Nutrition Examination Survey (NHANES) data from 1996 to 2006, the likelihood of adverse lipid values was higher in adolescents with greater body mass index (BMI). The prevalence among youths who were healthy weight, overweight (BMI 85^th to 95^th percentile), and obese (BMI >95^th percentile) were 14, 22, and 43 percent, respectively [15]. However, lipid abnormalities are also common in youth with normal weight. In an analysis of 12- to 19-year-olds enrolled in NHANES from 1988 to 2016, approximately 52 percent of those with high TC, 38 percent of those with low HDL-C, and 41 percent of youth with high non-HDL-C had a BMI in the normal weight range [16].

Reported rates of pediatric dyslipidemia in other countries are generally comparable to those in the US, including similar relationships to obesity [17,18].

Lipid levels have improved over time. In an analysis of NHANES data from 1999 and 2016, favorable temporal trends were observed in mean lipid levels and in the distribution of ideal and adverse lipid levels among youths aged 6 to 19 years [14]. Mean TC level declined from 164 mg/dL in 1999-2000 to 155 mg/dL in 2015-2016; mean HDL-C level increased from 52.5 mg/dL in 2007-2008 to 55.0 mg/dL in 2015-2016. Trends were generally consistent across racial/ethnic groups and BMI categories. Despite these favorable trends, it was estimated at the end of the study period that only one-half of youths in the United States had all lipids at ideal levels and approximately one in five had at least one adverse level.

ETIOLOGY — 

The etiology of dyslipidemia can be categorized as follows [19]. In some patients, dyslipidemia may be caused by more than one of these mechanisms.

●Dietary causes – Excessive dietary intake of saturated and trans fats is an important cause or contributor to elevated low-density lipoprotein and excessive intake of refined carbohydrates and simple sugars raises triglyceride levels. (See "Dyslipidemia in children and adolescents: Management", section on 'Dietary modification'.)

●Secondary causes – Many specific diseases and conditions are associated with dyslipidemia. Common secondary causes include obesity, type 2 diabetes mellitus, hypothyroidism, and nephrotic syndrome. Other secondary causes of dyslipidemia are summarized in the table and are discussed in greater detail separately (table 3). (See "Secondary causes of dyslipidemia".)

●Genetic causes – This includes monogenic and polygenic defects (table 4):

•Familial hypercholesterolemia (FH) is a monogenic condition characterized by elevated low-density lipoprotein cholesterol (LDL-C), most commonly caused by mutations in the LDL-receptor, PCSK9, or apolipoprotein B genes. (See "Familial hypercholesterolemia in children".)  

•Some patients may have a clinical phenotype similar to that of FH but without a single mutation of sufficient pathogenicity to produce it. Such patients likely have multiple gene variants, each of which makes a small independent contribution. These patients are said to have polygenic hypercholesterolemia. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia", section on 'Polygenic hypercholesterolemia'.)

•Familial chylomicronemia syndrome is a monogenic cause of severe hypertriglyceridemia, most frequently due to lipoprotein lipase (LPL) deficiency. (See "Hypertriglyceridemia in adults: Approach to evaluation", section on 'Severe hypertriglyceridemia'.)

RATIONALE FOR LIPID SCREENING

Benefits of screening — Screening for lipid disorders in childhood is based on the rationale that early identification and control of pediatric dyslipidemia will reduce the risk and severity of atherosclerotic cardiovascular disease (ASCVD) in adulthood [1]. Lipid disorders are clinically silent in the vast majority of cases, and selective screening alone (ie, screening only children with a positive family history) fails to identify a substantial number of children with lipid disorders.

●Early identification of individuals with FH – The rationale for universal screening is based, in large part, on the possibility of identifying and treating the greatest number of individuals with familial hypercholesterolemia (FH), a group at high risk for significant morbidity and early mortality [20]. (See "Familial hypercholesterolemia in children".)

●Prevention of ASCVD – There are no randomized trials evaluating the long-term effectiveness of screening for and treating dyslipidemia in childhood, and few data are available on the cost-effectiveness of pediatric lipid screening [21]. The evidence supporting the potential benefits of lipid screening in children comes from studies demonstrating links between pediatric dyslipidemia and early ASCVD.

Dyslipidemia often begins in childhood and adolescence. Pediatric dyslipidemia contributes to early atherosclerosis and, by extrapolation, to premature ASCVD [1,10]. Moreover, in the high-risk subset of children with severe dyslipidemia due to FH, treatment reduces the risk of cardiovascular events. (See "Familial hypercholesterolemia in children".)

Evidence for the development of atherosclerosis in childhood comes from longitudinal studies showing associations between dyslipidemia in childhood/adolescence and development of clinical ASCVD in adulthood. In a study comprised of data from seven different longitudinal studies including >11,000 participants who had lipid levels measured in adolescence and were then followed into adulthood, elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were both independent predictors of ASCVD events in adulthood (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) [22]. By age 50 years, 5.3 percent of participants who had elevated TC in adolescence had experienced at least one ASCVD event compared with 4.3 percent of those with normal TC in adolescence (adjusted hazard ratio 1.79, 95% CI 0.39-2.31).

Additional evidence comes from autopsy studies showing atherosclerotic changes in the young and studies demonstrating preclinical atherosclerotic vascular changes on using noninvasive imaging in children, adolescents, and young adults. These data are discussed separately. (See "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)", section on 'Association between pediatric risk factors and adult ASCVD'.)

Pediatric lipid disorders often track into adulthood. Approximately one-half of children with abnormal TC and LDL-C levels continue to have elevated TC and LDL-C in adulthood [1,19,23,24]. Children with severely elevated TC and LDL-C levels consistent with FH show stronger tracking to adulthood. Children's lipid values correlate with those of adult family members, and children with dyslipidemia are more commonly found in families with ASCVD [25]. Cumulative exposure to dyslipidemia appears to be closely correlated with ASCVD risk later in life. (See "Familial hypercholesterolemia in children" and "Familial hypercholesterolemia in adults: Overview".)

Additional evidence for the impact of lifetime cumulative LDL-C exposure comes from studies of individuals with genetic polymorphisms in the genes that control LDL-C catabolism. For example, individuals with PCSK9 gene polymorphisms associated with loss of function have low LDL-C levels, and this is associated with low lifetime risk of coronary artery disease. By contrast, lifetime exposure to high LDL-C levels due to gain-of-function variants in the same gene is associated with high ASCVD risk. (See "Familial hypercholesterolemia in adults: Overview", section on 'Mutations in the PCSK9 gene'.)

An important part of the rationale for lipid screening in childhood and adolescence is to facilitate early intervention for those who are found to have elevated LDL-C, including lifestyle interventions and statin therapy, if warranted. Studies supporting the efficacy of these interventions for pediatric dyslipidemia are discussed separately. (See "Dyslipidemia in children and adolescents: Management", section on 'Heart-healthy lifestyle' and "Dyslipidemia in children and adolescents: Management", section on 'Statin therapy' and "Familial hypercholesterolemia in children", section on 'Management'.)

●Family history: Insensitive predictor – A positive family history of premature ASCVD (ie, heart attack, treated angina, interventions for coronary artery disease, stroke, or sudden cardiac death in a male parent or sibling before 55 years of age or a female parent or sibling before 65 years of age) doubles the risk of ASCVD in children and is a well-established ASCVD risk factor in adults [26,27]. However, when used as the sole basis for selective screening in children, positive family history is an insensitive predictor of dyslipidemia.

Selective screening based on family history alone misses a considerable number (30 to 60 percent) of children with dyslipidemia [1,28,29]. In a population-based study of >20,000 5^th grade children, the prevalence of abnormal LDL-C levels was similar in children with or without a positive family history [30].

The widespread use of statin therapy in adults for primary prevention of ASCVD has lowered the rate of clinical cardiovascular events, which may explain why family history of premature ASCVD is less predictive of pediatric dyslipidemia than was previously thought.

Despite its limitations as the sole basis for screening, family history is an important consideration, and children with a positive family history should undergo selective screening for dyslipidemia earlier than the recommended universal screening timeframe. A detailed family history is particularly important when evaluating children with possible FH. (See 'Approach to screening' below and "Familial hypercholesterolemia in children".)

Harms of screening — In the absence of direct long-term data demonstrating that lipid screening in childhood leads to reduced ASCVD in adulthood, some experts have raised concerns that screening may identify a large number of patients who may be harmed by further diagnostic testing and/or initiation of drug therapy with uncertain benefit [31-35].

It is estimated that 100,000 children <17 years and >400,000 adolescents and young adults aged 17 to 21 years in the United States would qualify for statin therapy based on the National Heart, Lung, and Blood Institute screening recommendations [36-38]. Statin treatment may be beneficial for these patients. However, the potential risks of statin therapy in this population must also be considered. In pediatric trials, statins were generally well tolerated. Rare but important side effects of statin therapy include myopathy, new-onset type 2 diabetes mellitus, and hepatic enzyme elevation. These are discussed separately. (See "Dyslipidemia in children and adolescents: Management", section on 'Adverse effects' and "Statins: Actions, side effects, and administration", section on 'Side effects'.)

APPROACH TO SCREENING — 

The following sections outline our suggested approach to screening for dyslipidemia during childhood and adolescence. We use an approach that combines universal, selective, and cascade screening strategies.

Our approach is generally consistent with the guidelines of the National Heart, Lung, and Blood Institute, the American Academy of Pediatrics, the American Heart Association, and the American College of Cardiology [1,9-11]. However, this approach is not universally accepted. A 2023 report of the United States Preventive Services Task Force, after review of the available literature, concluded that data were insufficient to recommend for or against routine screening in children and adolescents [28]. The 2008 National Institute for Health and Care Excellence guidelines and the 2015 consensus statement of the European Atherosclerosis Society recommend selective screening and cascade screening to identify children and adults with FH [39,40]. Links to these and other published guidelines are provided separately. (See 'Society guideline links' below.)

Who should be screened — We suggest using a combined approach of universal and selective screening based on the age of the child and the presence of underlying risk factors that increase the risk of early atherosclerotic cardiovascular disease (ASCVD) (algorithm 1).

●Children with ASCVD risk factors – For children with one or more risk factors for premature ASCVD (table 5), we suggest regular screening for dyslipidemia. Screening typically begins at the age when the ASCVD risk factor is first identified. For children with diabetes mellitus, screening should be performed near the time of diagnosis but after glycemic control is well established. In the case of a family history of hypercholesterolemia or premature atherosclerotic ASCVD, screening typically begins after the age of two years. The interval of subsequent surveillance testing is tailored to the individual's risk profile (typically every one to three years) and continues so long as the risk factor(s) persist.

●Children with close relatives with known monogenic lipid disorders – For children with a first-degree relative (parent or sibling) or second-degree relative (grandparent, aunt, uncle) with a known genetic lipid disorder, such as familial hypercholesterolemia, we recommend cascade testing either with lipid testing as below, or if a molecular diagnosis has been made, testing for the specific identified genetic variant. This issue is discussed in greater detail separately. (See "Familial hypercholesterolemia in children", section on 'Testing family members'.)

●Children without ASCVD risk factors – For children without any risk factors for premature ASCVD, we suggest routine screening for dyslipidemia twice during childhood and late adolescence. The first screening should be performed between age 9 and 11 years and the second between age 17 and 21 years. Between ages 12 and 16 years, screening is not recommended for children without ASCVD risk factors, because changes in lipid levels that normally occur during puberty decrease the sensitivity and specificity for predicting adult low-density lipoprotein cholesterol (LDL-C) levels and increase false-negative results in this age group.

Choice of screening test — Lipid levels can be measured either in a fasting or nonfasting state. Treatment decisions are generally made based on fasting lipid profiles; however, screening can be accomplished with nonfasting lipid levels. If the initial screen is performed with a nonfasting test and the result is abnormal, a follow-up fasting lipid profile should be obtained. At least two fasting profiles should be used to guide clinical decision-making, including pharmacologic therapy. (See 'Follow-up after screening' below.)

●Lipid profile – The full lipid profile includes:

•Total cholesterol (TC), measured directly

•High-density lipoprotein cholesterol (HDL-C), measured directly

•Triglycerides (TG), measured directly – Since TG levels are influenced by recent food intake, treatment decisions should be based on fasting levels

•LDL-C, calculated using the Friedewald formula (calculator 1), Sampson-National Institutes of Health (NIH) Equation, or the Martin-Hopkins equation [41-43]

Nonfasting lipid levels often are more practical as a screening test for pediatric patients because many patients and families find it challenging to comply with fasting. Differences in TC and HDL-C measurements between the fasting or nonfasting state are small and clinically insignificant [44]. The nonfasting non-HDL-C level (which is calculated based on the difference between TC and HDL-C) appears to be a sensitive screening test for dyslipidemia in children [45]. Non-HDL-C includes all cholesterol present in lipoprotein particles that are considered atherogenic, including LDL-C, lipoprotein(a), intermediate-density lipoprotein, and very-low-density lipoprotein.

In an analysis from the Bogalusa study, non-HDL-C was at least as good a predictor as other lipid tests (ie, LDL-C, TC, HDL-C, and the ratio of TC:HDL-C) for predicting increased carotid intima-media thickness (an indirect marker for atherosclerosis) [46]. Another report from the Bogalusa study found that abnormal levels of childhood non-HDL-C persisted into adulthood and were predictive of adult dyslipidemia independent of baseline body mass index (BMI) and BMI changes over 27 years [45].

In the Pathobiological Determinants of Atherosclerosis in Youth study (PDAY study), non-HDL-C and HDL-C levels were the best lipid predictors of pathologic atherosclerotic lesions in autopsies of children who had died from noncardiac causes [47].

Of note, the Friedewald formula, which is used to calculate LDL-C levels in the fasting lipid profile is valid only if the TG level is <400 mg/dL (<4.5 mmol/L). The Sampson-NIH equation can be used for patients with TG levels up to 800 mg/dL [43]. In patients with more pronounced hypertriglyceridemia, LDL-C levels can be measured directly (direct LDL-C). We do not routinely use direct LDL as a screening test because non-HDL-C performs well, is readily available, and is less costly [48,49]. (See "Measurement of blood lipids and lipoproteins", section on 'Measurement'.)

FOLLOW-UP AFTER SCREENING — 

After the initial screening test, repeat testing is required for those with abnormal results to confirm the diagnosis of pediatric dyslipidemia and determine the need for intervention (algorithm 2).

Normal screen — Patients with "acceptable" values on lipid screening (table 2) do not require any further evaluation. They should continue to undergo regular cardiovascular health assessments, including lipid screening at the intervals outlined above (algorithm 1). (See 'Approach to screening' above.)

Borderline screen — For patients with borderline lipid results, recommendations for a heart-healthy lifestyle should be reinforced as for all children and adolescents. Further follow-up and testing is tailored to the specific clinical scenario. Important considerations include the age of the patient and underlying medical conditions or other risk factors (table 5). In most cases, it is reasonable to repeat testing in one year. (See "Dyslipidemia in children and adolescents: Management", section on 'Dietary modification' and "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children".)

Abnormal screen — Patients with adversely high or low values on the initial lipid screening test (table 2) should have confirmatory testing performed with a fasting lipid profile. If dyslipidemia is confirmed, patients should undergo evaluation for secondary causes of dyslipidemia. (See 'Confirmatory testing' below and 'Secondary causes of hypercholesterolemia' below.)

Confirmatory testing — The diagnosis of dyslipidemia requires confirmation testing with fasting lipid profiles obtained on two separate occasions two weeks to three months apart [1]. Decisions regarding the need for pharmacotherapy should be based on the results of at least two low-density lipoprotein cholesterol (LDL-C) values derived from fasting lipid profiles. Counseling regarding dietary and other lifestyle changes should begin with the first abnormal test. (See "Dyslipidemia in children and adolescents: Management".)

Repeated testing is required because there is considerable intraindividual variability. In a report from the Bogalusa study, children with LDL-C levels between 160 and 189 mg/dL (4.1 and 4.9 mmol/L) demonstrated an average decrease in LDL-C by 21 mg/dL (0.5 mmol/L) at the next examination and, among those with levels ≥190 mg/dL (≥4.9 mmol/L), the average decrease was 34 mg/dL (0.9 mmol/L) [50]. Patients and families should be counseled in lifestyle modification to promote normalization of values between testing. (See "Dyslipidemia in children and adolescents: Management", section on 'Heart-healthy lifestyle'.)

Secondary causes of hypercholesterolemia — Patients with confirmed dyslipidemia should be evaluated for secondary causes of hypercholesterolemia, which include (table 3):

●Diabetes mellitus, particularly uncontrolled disease (see "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Cardiovascular disease')

●Nephrotic syndrome (see "Clinical manifestations, diagnosis, and evaluation of nephrotic syndrome in children")

●Hypothyroidism (see "Acquired hypothyroidism in childhood and adolescence")

●Pregnancy (see "Approach to evaluating pregnant patients with elevated liver biochemical and function tests")

●Hepatic disease (see "Metabolic dysfunction-associated steatotic liver disease in children and adolescents")

●Drugs (eg, alcohol, glucocorticoids, isotretinoin, antiretrovirals) (see "Major adverse effects of systemic glucocorticoids", section on 'Cardiovascular effects' and "Oral isotretinoin therapy for acne vulgaris", section on 'Hyperlipidemia')

Many of these conditions can be identified through the history and physical examination. Additional laboratory evaluation may include serum alanine aminotransferase, serum albumin, blood glucose level, kidney function tests (ie, blood urea nitrogen and creatinine), serum thyroid-stimulating hormone, and urine human chorionic gonadotropin screen, if clinically indicated.

Criteria for referral — Referral to a pediatric lipid specialist may be warranted for some children with abnormal lipid screening results, as described below. A pediatric lipid specialist is typically pediatric cardiologist (or an endocrinologist, gastroenterologist, or general pediatrician), who has completed additional training in lipid disorders through a senior fellowship or via professional societies. If a pediatric lipid specialist is not available locally, referral to an adult lipid specialist may be helpful, particularly for adolescents.

Referral to a pediatric lipid specialist is generally warranted for children and adolescents with any of the following:

●Clinical suspicion of familial hypercholesterolemia (FH) – The LDL-C values that should raise suspicion for FH is ≥160 mg/dL (4.1 mmol/L) if there is a family history of premature atherosclerotic cardiovascular disease (ASCVD), or ≥190 mg/dL (4.9 mmol/L) in the absence of a family history of premature ASCVD. Other clinical findings that may raise clinical suspicion for FH (tendon xanthomas, premature ASCVD) are discussed separately. (See "Familial hypercholesterolemia in children", section on 'Clinical suspicion'.)

●Extreme hypertriglyceridemia – Patients with extremely elevated triglyceride (TG) levels (>1000 mg/dL [11.3 mmol/L]) should be referred to a lipid specialist, since TG levels in this range suggest the possibility of a primary genetic hypertriglyceridemia.

●LDL-C ≥130 mg/dL (3.4 mmol/L) in the setting of a high-risk condition – Referral is generally appropriate for patients with conditions that put them at high risk for early ASCVD (table 6) who despite optimal management of the underlying condition have LDL-C levels that warrant lipid-lowering pharmacotherapy (ie, LDL-C ≥130 mg/dL [3.4 mmol/L]).

DIFFERENCES IN PEDIATRIC VERSUS ADULT APPROACHES — 

There are two key differences between the pediatric approach to lipid screening, described above (see 'Approach to screening' above), and adult primary prevention approaches, which are discussed separately (see "Screening for lipid disorders in adults"):

●Global versus individual risk assessment – Adult primary prevention treatment recommendations are based in part on calculating a patient's individual baseline risk for atherosclerotic cardiovascular disease (ASCVD) by using validated risk scores (eg, PREVENT or ASCVD Risk Estimator Plus), which were developed from robust longitudinal data. (See "Cardiovascular disease risk assessment for primary prevention: Risk calculators" and "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'CVD risk assessment'.)

Scoring systems for estimating ASCVD risk in children are not available, because similar robust longitudinal data are generally lacking. Therefore, it is not possible to accurately estimate a child's individual risk for ASCVD.

●Lifetime versus 10-year risk – There are two approaches to assessing ASCVD risk in adults: the 10-year risk and the "lifetime" (eg, 30-year) risk [51]. The lifetime risk approach is more relevant to pediatric practice since the 10-year risk of ASCVD in children and adolescents is exceedingly low. Adult risk assessment scores, which were developed based on the ASCVD risk in a general population, should not be used in individuals with heterozygous familial hypercholesterolemia (FH) who have a lifetime risk for ASCVD events that is not adequately captured by these scores [52,53].

The differences in these two approaches may result in a discrepancy of recommendations regarding statin therapy as older adolescents transition their care from pediatric to adult primary care clinicians [38]. The "right" approach to treating lipid disorders in young adults remains to be determined.

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

●Definitions – Dyslipidemias are disorders of lipoprotein metabolism that result in one or more of the following abnormalities (table 2) (see 'Introduction' above and 'Definition of pediatric dyslipidemia' above):

•Total cholesterol (TC) ≥200 mg/dL (5.2 mmol/L)

•Low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL (3.4 mmol/L)

•Non-high-density lipoprotein cholesterol (non-HDL-C) ≥145 mg/dL (3.8 mmol/L)

•HDL-C <40 mg/dL (1.0 mmol/L)

•Triglycerides (TG) ≥100 mg/dL (1.1 mmol/L) in children <10 years and ≥130 mg/dL (1.5 mmol/L) in children >10 years

●Etiology – Pediatric dyslipidemia can be caused by any of the following mechanisms, alone or in combination (see 'Etiology' above):

•Excessive dietary intake of saturated and trans fats (see "Dyslipidemia in children and adolescents: Management", section on 'Dietary modification')

•Secondary causes such as obesity, type 2 diabetes mellitus, and nephrotic syndrome (table 3) (see "Secondary causes of dyslipidemia")

•Genetic causes, including monogenetic and polygenic defects (see "Familial hypercholesterolemia in children" and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia")

●Rationale for screening – Dyslipidemia often begins in childhood and adolescence and tracks into adulthood. Pediatric dyslipidemia contributes to early atherosclerosis and, by extrapolation, to premature atherosclerotic cardiovascular disease (ASCVD). In the high-risk subset of children with severe dyslipidemia due to familial hypercholesterolemia (FH), treatment reduces the risk of cardiovascular events. Screening for lipid disorders in childhood is based on the rationale that early identification and control of pediatric dyslipidemia will reduce the risk and severity of ASCVD in adulthood. (See 'Benefits of screening' above.)

●Approach to screening – Our approach to screening for dyslipidemia in children and adolescents uses a strategy of combined age-based universal and selective screening (algorithm 1) (see 'Approach to screening' above):

•Children with risk factors – For children with one or more risk factors for premature ASCVD (table 5), we suggest regular screening for dyslipidemia (Grade 2C). Screening typically begins at the age when the ASCVD risk factor is first identified (generally, not earlier than age two years, unless there is clinical suspicion for homozygous FH). The interval of testing is tailored to the individual's risk profile (typically, every one to three years) and continues so long as the risk factor(s) persist. (See 'Who should be screened' above.)

•Children without risk factors – For children without any risk factors for premature ASCVD, we suggest routine screening for dyslipidemia twice during childhood and late adolescence (Grade 2C). The first screening should be performed between age 9 and 11 years and the second between age 17 and 21 years. Screening should not be performed at age 12 to 16 years in children without ASCVD risk factors, because changes in lipid levels that normally occur during puberty decrease the sensitivity and specificity of screening. (See 'Who should be screened' above.)

•Choice of screening test – Lipid screening can be performed with a full fasting lipid profile or with nonfasting lipid levels (with the latter, non-HDL-C is calculated based on the TC and HDL-C levels). Abnormal results require confirmatory testing. (See 'Choice of screening test' above.)

●Follow-up after screening

•Repeat lipid profile – For patients with abnormal results, repeat testing is performed with a fasting lipid profile to confirm the diagnosis and determine the need for intervention (algorithm 2). (See 'Confirmatory testing' above.)

•Evaluation for secondary causes – Patients with confirmed dyslipidemia should be evaluated for secondary causes of hypercholesterolemia, which include diabetes mellitus, nephrotic syndrome, hypothyroidism, pregnancy, hepatic disease, and certain medications (table 3). (See 'Secondary causes of hypercholesterolemia' above.)

●Referral – Referral to a pediatric lipid specialist is generally warranted for children and adolescents with any of the following (see 'Criteria for referral' above):

•Clinical suspicion of FH – FH should be suspected if the LDL-C is ≥160 mg/dL (4.1 mmol/L) in the setting of a family history of premature ASCVD, or LDL-C ≥190 mg/dL (4.9 mmol/L) in the absence of a family history of premature ASCVD. (See "Familial hypercholesterolemia in children", section on 'Clinical suspicion'.)

•Extremely elevated TG levels (>1000 mg/dL [11.3 mmol/L]), since TG levels in this range suggest the possibility of a primary genetic hypertriglyceridemia.

•LDL-C ≥130 mg/dL (3.4 mmol/L) in the setting of a high-risk condition – Referral is generally appropriate for patients with conditions that put them at high risk for early ASCVD (table 6) who despite optimal management of the underlying condition have LDL-C levels that warrant lipid-lowering pharmacotherapy (ie, LDL-C ≥130 mg/dL [3.4 mmol/L]).

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Jane Newburger, MD, MPH, who contributed to earlier versions of this topic review.