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 cardiovascular disease (CVD), and correcting dyslipidemia reduces the risk of CVD. 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 CVD.
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, diagnosis and management of familial hypercholesterolemia (FH), other inherited disorders of cholesterol, and screening for lipid disorders in adults are reviewed separately:
●(See "Dyslipidemia in children and adolescents: Management".)
●(See "Familial hypercholesterolemia in children".)
●(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.
African American children have higher TC and HDL cholesterol (HDL-C) levels and lower triglyceride levels compared with other racial/ethnic groups. However, the levels do not appear to be associated with differences in preclinical atherosclerosis in childhood (as measured by carotid intima-media thickness).
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).
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 cardiovascular disease (CVD) events.
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 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
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 normal weight, overweight (BMI 85th to 95th percentile), and obese (BMI >95th percentile) were 14, 22, and 43 percent, respectively [15].
Similar rates of pediatric dyslipidemia with similar relationships to obesity have been reported in other countries [16,17].
In another study based on 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 [18]. 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 dyslipidemia. (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, 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 monogenetic and polygenic defects:
•Monogenic conditions include familial hypercholesterolemia (FH), familial defective apolipoprotein B or PCSK9, and familial hypertriglyceridemia. (See "Familial hypercholesterolemia in children" and "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia" and "Hypertriglyceridemia in adults: Management".)
•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'.)
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 cardiovascular disease (CVD) 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. (See 'Family history: Insensitive predictor' below.)
Randomized controlled trials evaluating the long-term effectiveness of screening and treatment in childhood are lacking, and no data are available on the cost-effectiveness of pediatric lipid screening methods. The evidence supporting the potential benefits of screening and treatment in children comes from short-term trials in high-risk populations and studies demonstrating links between pediatric dyslipidemia and atherosclerosis. (See 'Association with atherosclerosis and cardiovascular disease' below.)
The rationale for universal screening is based, in 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 [19]. (See "Familial hypercholesterolemia in children".)
The approach described below of combined universal and selective screening for dyslipidemia during childhood and adolescence 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 2016 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 infants, children, adolescents, or young adults [20]. 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 [21,22]. These and other published guidelines can be accessed through the links provided below. (See 'Society guideline links' below.)
Association with atherosclerosis and cardiovascular disease — Dyslipidemia often begins in childhood and adolescence. Pediatric dyslipidemia contributes to early atherosclerosis and, by extrapolation, to premature CVD [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 includes autopsy studies showing atherosclerotic changes in the young and noninvasive, indirect data in children and adolescents showing vascular changes that commonly precede adult CVD. This evidence is discussed in greater detail separately. (See "Overview of risk factors for development of atherosclerosis and early cardiovascular disease in childhood", section on 'Atherosclerotic changes in childhood'.)
Pediatric lipid disorders often track into adulthood. Approximately one-half of children with abnormal serum lipoprotein values continue to have elevated lipid levels in adulthood [1,18,23,24]. Children with severely elevated lipid values consistent with familial hyperlipidemia show stronger tracking to adulthood. Cumulative exposure to dyslipidemia appears to be associated with cardiovascular risk later in life. (See "Familial hypercholesterolemia in children" and "Familial hypercholesterolemia in adults: Overview".)
Children's lipid values correlate with those of adult family members, and children with dyslipidemia are more commonly found in families with CVD [25].
Lifetime low low-density lipoprotein cholesterol (LDL-C) resulting from genetic defects (eg, PCSK9 gene polymorphisms associated with loss of function) is associated with low lifetime risk of coronary artery disease, while lifetime high LDL-C due to gain-of-function mutations is associated with high CVD risk. (See "Familial hypercholesterolemia in adults: Overview", section on 'Mutations in the PCSK9 gene'.)
Family history: Insensitive predictor — A positive family history of premature CVD (ie, heart attack, treated angina, interventions for coronary artery disease, stroke, or sudden cardiac disease 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 CVD in children and is a well-established CVD 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 [1,20,28]. In a population-based study of >20,000 5th grade children, the prevalence of abnormal LDL-C levels was similar in children with or without a positive family history [29].
The widespread use of statin therapy in adults for primary prevention of CVD has lowered the rate of clinical cardiovascular events, which may explain why family history of premature CVD 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 CVD 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 [30-34].
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 [35-37]. These patients may benefit from statin treatment for high LDL-C. The potential risks of statin therapy in this population must also be considered. Rare but important side effects of statin therapy in adults include rhabdomyolysis and new-onset type 2 diabetes mellitus. Adverse effects of statin therapy in children are rare and 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'.)
More data are needed to address these important questions and to determine whether there is overall benefit for universal screening of pediatric dyslipidemia.
APPROACH TO SCREENING
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 cardiovascular disease (CVD) risk factors (algorithm 1).
●Children with CVD risk factors – For children with one or more risk factors for premature CVD (table 4), we suggest regular screening for dyslipidemia. Screening typically begins at the age when the CVD risk factor is first identified. In the case of a family history of hypercholesterolemia or premature atherosclerotic CVD, 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 without CVD risk factors – For children without any risk factors for premature CVD, 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. At age 12 to 16 years, screening is not recommended for children without CVD 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 screening can be performed with a full fasting lipid profile or with nonfasting lipid levels (with the latter, non-high-density lipoprotein cholesterol [non-HDL-C] is calculated based on directly measured total cholesterol [TC] and HDL-C levels). Data from the National Health and Nutrition Examination Surveys (1999 to 2008) demonstrate only small differences between nonfasting and fasting lipid measurements that are likely clinically insignificant [38]. If an initial nonfasting screen 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.)
The full lipid profile includes direct measurement of TC, HDL-C, and triglycerides. Triglyceride levels are influenced by recent food intake and should be measured in the fasting state when possible. In contrast, differences in measurements of TC and HDL-C between the fasting or nonfasting state are small and clinically insignificant. LDL-C levels reported in the lipid profile are generally calculated using the Friedewald formula (calculator 1). The formula is valid only if the triglyceride level is <400 mg/dL (<4.5 mmol/L). In patients with more pronounced hypertriglyceridemia, LDL-C levels must be measured directly (direct LDL). However, we do not routinely use direct LDL as a screening test, because of systematic biases in these assays compared with fasting lipid profiles and because normative values are based on the calculated LDL-C [39,40]. (See "Measurement of blood lipids and lipoproteins", section on 'Measurement'.)
Non-HDL-C is the difference between the TC and HDL-C. 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. TC and HDL-C can be measured accurately in plasma from nonfasting individuals, making it a more practical screening test for pediatric patients than a fasting lipid profile.
The nonfasting non-HDL-C level appears to be a sensitive screening test for dyslipidemia in children. 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) [41]. 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 [42].
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 [43].
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). Very high cholesterol values are suggestive of familial hypercholesterolemia (FH) and generally warrant additional evaluation. (See "Familial hypercholesterolemia in children", section on 'Evaluation and diagnosis'.)
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 4). 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 and, if dyslipidemia is confirmed, 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 low-density lipoprotein cholesterol (LDL-C) values derived from averaging the results of the two fasting lipid profiles. However, 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) [44]. 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 on two separate fasting lipid profiles should be evaluated for secondary causes of hypercholesterolemia, which include (table 3):
●Diabetes mellitus, particularly uncontrolled disease (see "Complications and screening in children and adolescents with type 1 diabetes mellitus", section on 'Cardiovascular disease')
●Nephrotic syndrome (see "Etiology, clinical manifestations, and diagnosis 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 "Nonalcoholic fatty liver disease in children and adolescents")
●Drugs (eg, alcohol, glucocorticoids, isotretinoin, antiretrovirals) (see "Major side 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, renal function tests (ie, blood urea nitrogen and creatinine), serum thyroid-stimulating hormone, and urine human chorionic gonadotropin screen, if clinically indicated.
Very high cholesterol (LDL-C 250 or higher) — Children with LDL-C ≥250 mg/dL (6.5 mmol/L) should be referred directly to a pediatric lipid specialist for further evaluation and management. Referral may ultimately be necessary if LDL levels remain elevated (≥160 mg/dL despite adequate lifestyle modification counseling). Markedly elevated cholesterol levels are associated with a high likelihood of FH and almost certainly require pharmacotherapy. (See "Familial hypercholesterolemia in children".)
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 cardiovascular disease (CVD) by using validated risk scores (eg, the Framingham and the Reynolds risk scores, and the American College of Cardiology/American Heart Association guidelines [45]), which were developed from robust outcome data. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'CVD Risk Assessment' and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)
Scoring systems for estimating CVD risk in children are not available, because similar robust outcomes data are generally lacking. Therefore, it is not possible to accurately estimate a child's individual risk for CVD.
●Lifetime versus 10-year risk – There are two approaches to assessing CVD risk in adults: the 10-year risk and the "lifetime" (eg, 30-year) risk [46]. The lifetime risk approach is more relevant to pediatric practice since the 10-year risk for children and adolescents is exceedingly low. Adult risk assessment scores, which were developed based on the CVD risk in a general population, should not be used in individuals with heterozygous familial hypercholesterolemia (FH) who have a lifetime risk for CVD events that is not adequately captured by these scores [47,48].
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 [37]. 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)
•Triglycerides >100 mg/dL (1.1 mmol/L) in children <10 years and >130 mg/dL (1.5 mmol/L) in children >10 years
•High-density lipoprotein cholesterol (HDL-C) <40 mg/dL (1.0 mmol/L)
•Non-HDL-C >145 mg/dL (3.8 mmol/L)
●Etiology – The etiology of pediatric dyslipidemia includes monogenic conditions (eg, familial hypercholesterolemia [FH]), secondary causes (table 3), and polygenic defects. (See 'Etiology' above.)
●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 cardiovascular disease (CVD). In the high-risk subset of children with severe dyslipidemia due to 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 CVD in adulthood. (See 'Benefits of screening' above and 'Association with atherosclerosis and cardiovascular disease' 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 CVD (table 4), we suggest regular screening for dyslipidemia (Grade 2C). Screening typically begins at the age when the CVD risk factor is first identified (generally, no earlier than age two years). 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 and adolescents without risk factors – For children and adolescents without any risk factors for premature CVD, 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 CVD 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 with a fasting lipid profile is required 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 – Children with LDL-C ≥250 mg/dL (6.5 mmol/L) should be referred directly to a pediatric lipid specialist since markedly elevated cholesterol levels are associated with a high likelihood of FH and almost certainly require pharmacotherapy. In addition, referral is warranted if LDL-C levels remain elevated (≥160 mg/dL) despite adequate lifestyle modification counseling. (See 'Very high cholesterol (LDL-C 250 or higher)' above and "Familial hypercholesterolemia in children".)
