Pediatric Lipid Disorders in Clinical Practice 

Updated: Jun 27, 2019
Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD 

Overview

Background

The early stages of atherosclerosis begin in childhood, according to multiple studies.[1] If premature development of cardiovascular disease can be anticipated during childhood, the disease might be prevented.[2] The purpose of this article is to discuss the basic biology of lipoproteins, the pathophysiology of dyslipidemias, the interpretation of lipid levels in pediatric patients, dyslipidemia screening, and the management of pediatric lipid abnormalities.

Patients and families should be educated about appropriate diet, activity levels, and risk factors. For patient education information, see the Cholesterol Center, as well as High Cholesterol and Children, Cholesterol-Lowering Medications, and Statins (Cholesterol Drugs). See also the Medscape Drugs and Diseases articles Hypertriglyceridemia, Familial Hypercholesterolemia, and Lipid Management Guidelines.

Pathophysiology

Physiology of lipids and lipoproteins

The two major forms of circulating lipid in the body, triglyceride (TG) and cholesterol, are insoluble in plasma. However, these lipids can be transported throughout the bloodstream as lipoproteins when packaged with phospholipids and proteins (apoproteins). Lipoproteins have an outer core of cholesterol, phospholipids, and apoproteins and an inner core composed of TG and cholesterol ester (CE). Apoproteins function as (1) structural proteins, (2) proteins that make the lipoprotein particle soluble, (3) enzyme activators (eg, apoprotein C-II activates lipoprotein lipase [LPL], apoprotein A-I activates lecithin-cholesterol acyltransferase [LCAT]), and (4) ligands for receptors (eg, apoprotein B-100 binds to the low-density lipoprotein receptor [LDL-R], which is also known as the apoprotein B-100 – apoprotein E receptor).

Lipoproteins have been classified into five major classes, as depicted in the table below.

Table 1. Biology of Lipoproteins (Open Table in a new window)

Lipoprotein

Major Lipid Composition

Role in Normal Fasting Plasma

Measured Substance

High-density lipoprotein cholesterol (HDL-C)

Cholesterol

Antiatherogenic (involved in reverse cholesterol transport from the tissues to the liver)

HDL-C

Low-density lipoprotein cholesterol (LDL-C)

Cholesterol

Major cholesterol carrier

Can be measured directly (direct LDL-C) or can be calculated*

Intermediate-density lipoprotein cholesterol (IDL-C)

TG and cholesterol

Intermediate between very low-density lipoprotein (VLDL) and LDL

Not routinely measured; can be assessed by lipoprotein electrophoresis (LPE) or measured by ultracentrifugation

VLDL

TG

Major TG carrier

TG†

Chylomicron

TG

Absent

Not routinely measured; can be assessed by LPE or measured by ultracentrifugation

* Calculated using the Friedewald equation: LDL-C = Total cholesterol (TC) - HDL-C - TG/5

† TG/5 is the estimate of the VLDL-C. 

 

The classes of lipoprotein are not homogeneous in size or composition. For example, low-density lipoprotein cholesterol (LDL-C) can be divided into cholesterol-rich light, or buoyant, LDL-C and cholesterol-depleted, or dense, LDL-C. Dense LDL-C is more atherogenic than light LDL-C.

Lipoproteins are derived from the exogenous and the endogenous pathways. In the exogenous pathway, dietary lipids are consumed with meals; these lipids (predominantly TGs) are packaged by the intestinal mucosal cells into chylomicrons. Chylomicrons, which are TG rich, enter the lymphatic system. The thoracic duct empties into the vena cava, and chylomicrons systemically circulate. Apoprotein C-II, apoprotein B-48, and apoprotein E are the clinically important apoproteins of chylomicrons.

Apoprotein B-48 is a chylomicron structural protein. Chylomicrons bind to LPL via apoprotein C-II. Once acted on by LPL, which is attached to the luminal side of the capillary endothelium adjacent to muscle and adipose tissue, chylomicrons release TGs as monoglycerides and free fatty acids. Defects in apoprotein C-II or LPL can lead to defects in chylomicron clearance. Muscle normally burns the free fatty acids and monoglycerides for energy. Resynthesized TGs can be used for plasma and cell organelle membrane synthesis. Adipose tissue uses free fatty acids and monoglycerides to resynthesize TGs that are stored for future energy needs. As an alternative, adipocytes can use TGs in membrane synthesis, which is similar to muscle.

When the chylomicrons are reduced in TG content, they become remnants that are rapidly cleared by the liver (apoprotein E binds to the LDL receptor [LDL-R]). At this time, apoprotein C-II is passed to high-density lipoprotein (HDL) particles in the circulation. In the fasting state, chylomicrons and chylomicron remnants are not normally detected in plasma.

In the endogenous pathway, the liver produces VLDL. The clinically important apoproteins in VLDL are apoprotein C-II, apoprotein B-100, and apoprotein E. Like chylomicrons, VLDL interacts with LPL via apoprotein C-II to release TG, forming intermediate-density lipoprotein (IDL) particles. With the formation of IDL, apoprotein C-II is transferred to HDL particles. IDL particles are rapidly removed by the liver via apoprotein E interaction with the LDL-R. IDL particles may be further metabolized to LDL by continued removal of TG by hepatic lipase.

In the conversion from IDL to LDL, apoprotein E is shed and is picked up by HDL particles. LDL is removed by binding to the LDL-R. Approximately two thirds of circulating LDL is removed by the liver, and approximately one third is removed by extrahepatic tissues, including steroid-producing cells and cells within the subintimal space in which atheromatous plaques develop. In the subintimal space, the protective effect of circulating antioxidants is lost, and LDL is oxidized.

Oxidized LDL is removed by the scavenger receptor, which is different from the LDL-R. Smooth muscle cells and macrophages express scavenger receptors. This uptake of LDL is not regulated, and macrophages and smooth muscle cells can take up so much oxidized LDL and cholesterol that they become foam cells. Because oxidized LDL is toxic to cells, it can lead to early endothelial injury, allowing platelet adhesion and localized release of platelet-derived growth factor (PDGF). In contrast, when other cells have sufficient cholesterol, they down-regulate the LDL-R to decrease cholesterol uptake into the cell.

Dyslipidemias

Table 2, below, depicts the Frederickson classification scheme, used to distinguish dyslipidemias.

Table 2. Frederickson Classification of Dyslipidemias (Open Table in a new window)

Phenotype

Elevated Particles

Major Lipid Increased

Frequency

I

Chylomicron

TG

Very rare

IIA

LDL

LDL-C

Common

IIB

LDL and VLDL

LDL-C, TG

Common

III

IDL and remnants

TC, TG

Rare

IV

VLDL

TG

Common

V

Chylomicron and VLDL

TG

Uncommon

IDL = intermediate-density lipoprotein; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides; VLDL = very low-density lipoprotein.

 

The most common dyslipidemias are types IIA, IIB, and IV. Type I and type III hyperlipoproteinemia (HLP) are extremely rare in pediatric patients, and type V is uncommon.

Type I HLP

Type I HLP is present when the TGs are predominantly elevated. TG levels may exceed 1000-2000 mg/dL, and levels as high as 25,000 mg/dL have been observed. Type I HLP is also termed chylomicron syndrome or hyperchylomicronemia syndrome. In type I HLP, the plasma infranatant on standing is clear, whereas the supernatant is cloudy because of elevated chylomicrons that float to the top of the plasma. Supernatants form only when chylomicrons are present. The presence of chylomicrons is best confirmed by obtaining plasma lipoprotein ultracentrifugation, performed by a referral laboratory that specializes in lipid analysis. Lipoprotein electrophoresis (LPE) is far less quantitative than ultracentrifugation.

Most cases of type I HLP are caused by congenital deficiency of LPL, congenital deficiency of apoprotein C-II, or an LPL inhibitor (eg, an anti-LPL autoantibody). In healthy children and adults, chylomicrons are rapidly cleared from the circulation after a meal. When LPL or apoprotein C-II is deficient, chylomicrons can be detected for more than 12 hours after a meal. The normal half-life of chylomicrons in plasma is approximately 17 minutes. Because TGs are not being cleared at the tissue level (eg, TG is not released from the chylomicrons to muscle and adipose tissue) in type I HLP, most chylomicrons are taken up by the liver and spleen, resulting in hepatosplenomegaly, macrophage uptake (foam cell formation), and the development of cutaneous xanthomas.

If prolonged hypertriglyceridemia is untreated, eruptive xanthomas (discrete 1-mm to 6-mm papules) may appear on the extensor surfaces of the extremities. Lipemia retinalis may also occur. The retinal vessels appear white-to-yellow in color because of the striking hyperchylomicronemia.

When TG levels exceed 1000-2000 mg/dL, the risk of pancreatitis is increased. Infants may present with colicky abdominal pain and even failure to thrive. In older children, acute pancreatitis can cause tremendous pain, nausea, vomiting, and even death if undetected and untreated. Recurrent pancreatitis can be debilitating.

In one study of patients with LPL deficiency, 80% presented before age 10 years, with 30% presenting before age one. In contrast, apoprotein C-II deficiency is usually diagnosed later in life (>13 years). Apoprotein C-II deficiency rarely presents in infancy.

At least 40 molecular defects in LPL and 12 different molecular defects in apoprotein C-II have been reported. Both LPL and apoprotein C-II deficiencies are inherited as autosomal recessive traits and affect approximately 1 in 1 million persons in the general population. Because LPL and apoprotein C-II deficiencies are inherited as autosomal recessive traits, the family history is generally unrevealing, although some parents of children with LPL or apoprotein C-II deficiency have been cousins. Carriers of LPL mutations are asymptomatic.

Note that lipemic serum can interfere with many laboratory determinations, including enzyme activity measurements, antigen-antibody assays, and various spectrophotometric assays.

Type II HLP

In children, type IIA HLP is defined by LDL-C concentrations of 130 mg/dL or higher. The plasma is clear in type IIA HLP because LDL particles are not large enough to scatter light, as opposed to IDL, VLDL, or lipoprotein remnants that are large enough to cause turbidity.

In type IIB HLP, TG levels (VLDL levels) are elevated to 125 mg/dL or higher, and LDL-C levels are also elevated. If the TG level is typically 300-400 mg/dL or higher, the plasma appears visibly turbid (lipemic).

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated LDL-C levels with or without a concurrent elevation in TG levels. Thus, individuals with FH may display a type IIA or B phenotype. FH affects approximately one in 500 persons in the general population. Besides premature cardiovascular disease, clinical findings in adults include tendon xanthomas (especially involving the Achilles tendons and the extensor tendons of the hands) and arcus senilis (involving the cornea). FH results from an inherited defect in the LDL-R. Because the LDL-R also clears IDL, and because VLDL is the precursor of IDL and LDL, patients with FH may also display elevations in IDL and VLDL.

If an individual inherits two defective alleles of the LDL-R gene (homozygous FH), LDL production increases by approximately 200-300%. Adults who are heterozygous for FH have two- to three-fold higher total cholesterol (TC) levels of 300-600 mg/dL, and LDL-C levels are commonly 250 mg/dL or higher. Patients who are homozygous for FH have TC levels of 600-1500 mg/dL. Homozygous FH leads to extremely premature and hazardous atherosclerosis. In addition, aortic valvar disease can occur in children with homozygous FH.

Besides valve dysfunction, the ostia of the coronary arteries can become obstructed. Fortunately, homozygous FH is very rare, affecting only one in 1 million persons. Children with homozygous FH have suffered myocardial infarctions as early as age 3 years. Death during adolescence is common. Homozygous FH should thus be strongly suspected in deaths from myocardial infarction in individuals aged 20 years or younger.

In heterozygous FH, affected family members have elevated LDL-C concentrations beginning early in life. Cord blood TC and LDL-C levels are already elevated. Untreated males with FH often develop cardiovascular disease in the fourth or fifth decade of life, but the disease can manifest in teenagers. The mean age of death in males with untreated FH is 45 years. Untreated women with FH usually have onset of cardiovascular disease in the fifth or sixth decade of life. Of persons who have survived myocardial infarctions that occurred when they were younger than 60 years, 5% have FH.

A defect in apoprotein B-100 is phenotypically similar to FH and occurs with a similar frequency. Elevated LDL-C levels result when the apoprotein B molecule is defective, even if the LDL-R molecule is normal. In FH, IDL and VLDL concentrations can be elevated because IDL is cleared via the LDL-R; however, in familial defective apoprotein B-100, because the LDL-R molecule is normal, IDL, VLDL, and TG levels are usually normal. In contrast to FH, tendon xanthomas and arcus senilis may be absent in patients with defective apoprotein B-100. Modest hypercholesterolemia (250-300 mg/dL) is usually present, with a TC level lower than in adults with FH (mean TC concentration in defective apoprotein B-100 is 269 mg/dL, vs approximately 360 mg/dL in FH). LDL-C levels are raised by approximately 70 mg/dL. As in FH, patients with familial defective apoprotein B-100 may develop premature cardiovascular disease.

Familial defective apoprotein B-100 and FH can be very difficult to clinically differentiate when patients with FH display a type IIA phenotype; however, in the absence of secondary conditions that raise TG levels, the presence of a type IIB phenotype essentially excludes familial defective apoprotein B-100.

Familial combined hyperlipidemia (FCH) is inherited as an autosomal dominant trait. The etiology of FCH appears to be an overproduction of apoprotein B–containing particles (VLDL, LDL, or both). Affected individuals may exhibit type IIA, type IIB, or type IV phenotypes. In a single family with FCH, some individuals may display isolated elevations in TC/LDL (type IIA HLP) or TG (type IV HLP) levels, whereas other affected members may have a combined hyperlipidemia (increased LDL-C and TG levels [type IIB HLP]). The co-occurrence of FCH plus hypertension has been called familial dyslipidemic hypertension. Similar to FH, premature cardiovascular disease can occur in patients with FCH. Overall, FCH affects approximately 1 in 200-300 persons in the general population and occurs in approximately 15% of individuals younger than 60 years who survive a myocardial infarction.

Other causes of type IIA or IIB phenotypes include hypothyroidism, nephrosis, biliary tract disease, and diabetes mellitus. In hypothyroidism, hepatic LDL-R expression is reduced, leading to elevated LDL-C levels because of reduced LDL clearance. Lipoprotein production is typically increased in patients with nephrosis. This may be a compensation for hypoalbuminemia. With glycation of apoprotein B in patients with diabetes mellitus and increased VLDL synthesis, LDL-C levels commonly rise.

Type III HLP

Type III HLP (also known as remnant removal disease, remnant lipoprotein disease, or dysbetalipoproteinemia) is estimated to affect approximately 1 in 5000 persons in the general population but rarely manifests in children. Type III HLP is caused by increases in IDL and remnant lipoproteins and is manifested by approximately equal increases in total cholesterol and TGs.

Palmar xanthomas (xanthoma striata palmaris) may occur in type III HLP and are not observed in other disorders. Genetic and environmental factors both influence the development of type III HLP. The entity should be considered when tuberous xanthomas, palmar xanthomas, or both are noted, and the patient may be obese or have underling diseases such as diabetes mellitus, hypothyroidism, alcoholism, and renal or hepatic disease. Type III HLP can be inherited as a recessive trait or, less commonly, as a dominant trait.

Most adults with type III HLP are homozygous for apoprotein E-2 (one of the 3 isoforms of apoprotein E). Adults with type III HLP are at markedly increased risk for cardiovascular disease and, particularly, peripheral vascular disease.

Type IV HLP

In type IV HLP, a predominant increase in VLDL TGs is observed; however, levels are lower (eg, < 1000 mg/dL) than in HLP types I or V.

Hypertriglyceridemia (usually the type IV HLP phenotype) is frequently observed in children with obesity, diabetes, or both conditions. In type 1 diabetes mellitus, hypertriglyceridemia results from absolute insulin deficiency, whereas in children with obesity and type 2 diabetes mellitus, insulin resistance is the root cause, combined with relative insulin deficiency. Other causes of insulin resistance, including renal disease, liver disease, ethanol abuse, pregnancy, endocrinopathies (eg, Cushing disease, hypothyroidism, acromegaly), and drugs (eg, glucocorticoids, growth hormone, androgens, thiazides, beta blockers, estrogen, HIV protease inhibitors), may also lead to hypertriglyceridemia.

Similar to insulin, thyroid hormone regulates LPL activity; hypothyroidism can cause elevated TG levels by lowering LPL activity.

The combination of type IV HLP and low HDL-C (eg, hypoalphalipoproteinemia) are typical findings in the metabolic syndrome. The metabolic syndrome is a constellation of findings related to reduced insulin sensitivity most commonly caused by centripetal and abdominal obesity. Besides dyslipidemia, features of the metabolic syndrome include hyperinsulinism, dysglycemia (eg, impaired glucose tolerance, impaired fasting glucose or type 2 diabetes), hypertension, hyperuricemia, hyperandrogenism in women, polycystic ovary syndrome, propensity to thrombosis (because of increased plasminogen activator inhibitor levels), and elevated ferritin concentrations. Adults with the metabolic syndrome are at greatly increased risk for cardiovascular disease.

Two inherited causes of a type IV phenotype include familial hypertriglyceridemia and FCH. Familial hypertriglyceridemia is rarely expressed in childhood unless another underlying cause of hypertriglyceridemia is present. About 15% of patients with premature cardiovascular disease have hypertriglyceridemia.

Type V HLP

Type V HLP results when two or more causes of type IV HLP combine to produce chylomicronemia and elevated VLDL levels, which push TG levels to 1000 mg/dL or higher. Plasma samples in patients with type V HLP display a turbid infranatant and a cloudy supernatant.

Other dyslipidemic syndromes

The differential diagnosis of a depressed HDL-C level includes familial disorders, genetic disorders, smoking, obesity, hypertriglyceridemia, renal failure, and drugs (eg, anabolic steroids, progestins, beta blockers, thiazides), with male sex and a sedentary lifestyle being additional risk factors for low HDL-C. In familial hypoalphalipoproteinemia (ie, low HDL-C) and Tangier disease, depressed apoprotein A-I levels are found. Other rare genetic causes of low HDL-C levels include fish-eye disease and lecithin-cholesterol acyl transferase (LCAT) deficiency. In fish-eye disease, patients have TG elevations to 250-300 mg/dL, severely depressed HDL-C levels, and corneal opacities. In LCAT deficiency, cholesterol esters cannot be formed; thus, cholesterol does not move into the core of the HDL particle disc.

Causes of acquired low LDL-C levels include malnutrition from starvation or malabsorption, hyperthyroidism, chronic anemia, severe hepatic dysfunction, and acute severe stress (eg, burns, trauma, myocardial infarction). Genetic forms of hypolipidemia are very rare but are potentially serious. Such conditions include abetalipoproteinemia (autosomal recessive), homozygous hypobetalipoproteinemia, heterozygous hypobetalipoproteinemia (with or without GI tract or neurologic symptoms), abetalipoproteinemia with normotriglyceridemia, and chylomicron retention disease. Low cholesterol levels secondary to deficiency of 7-dehydrocholesterol-δ-7 reductase are seen in Smith-Lemli-Opitz syndrome associated with mental retardation and ambiguous genitalia.

 

DDx

Diagnostic Considerations

Measure the fasting lipid profile twice and average the results if any of the following are noted:

  • Family history of premature cardiovascular disease

  • Family history of dyslipidemia

  • Pediatric medical condition that predisposes to cardiovascular disease or dyslipidemia

Pediatric conditions with an increased risk for cardiovascular disease include the following:

  • Lifestyle: Smoking (including exposure to secondary smoke), obesity (body mass index [BMI] > 95th percentile), physical inactivity

  • Metabolic disorders: Diabetes mellitus, low level of high-density lipoprotein cholesterol (HDL-C) (ie, < 35 mg/dL)

  • Hypertension and other underlying conditions or situations: Renal disease (eg, renal failure, renal transplantation), liver disease (eg, biliary tract disease), endocrinopathies (eg, hypothyroidism, Cushing syndrome), use of drugs known to induce dyslipidemias (eg, cyclosporine, glucocorticoids, human immunodeficiency virus [HIV] protease inhibitors)

 

Workup

Approach Considerations

The 2017 American Association for Clinical Endocrinology (AACE) and American College of Endocrinology (ACE) guidelines indicate the following points should be considered when interpreting lipid profiles in children and adolescents[3] :

  • Lipid levels fluctuate during childhood and adolescence: Although plasma cholesterol levels normally peak before puberty (age 9-11 y) in boys, they often decline during puberty, along with high-density lipoprotein cholesterol (HDL-C) values.
  • Low HDL-C may not have the same implications in children as it does in adults: Over 50% of children with low HDL-C levels have normal HDL-C levels as adults. Furthermore, low HDL-C values do not constitute a hallmark of the insulin resistance syndrome in children; in this population, obesity and hypertriglyceridemia are the best predictors of this condition.
  • Lipid levels vary by sex: Throughout childhood and adolescence, plasma cholesterol levels tend to be higher in girls than in boys.

Childhood obesity guidelines

The Endocrine Society, European Society of Endocrinology, and Pediatric Endocrine Society released guidelines on the assessment, treatment, and prevention of pediatric obesity in January 2017, as summarized below.[4, 5]

Children or teens with a body mass index (BMI) ≥85th percentile should be evaluated for related conditions such as metabolic syndrome, diabetes, prediabetes, or hypertension.

Youth being evaluated for obesity do not need to have their fasting insulin values measured, because it has no diagnostic value.

Children or teens affected by obesity do not need routine laboratory evaluations for endocrine disorders that can cause obesity unless their height or growth rate is less than expected based on age and pubertal stage.

About 7% of children with extreme obesity may have rare chromosomal abnormalities or genetic mutations. Specific genetic testing is suggested when there is early-onset obesity (before age 5 years), an increased drive to consume food known as extreme hyperphagia, other clinical findings of genetic obesity syndromes, or a family history of extreme obesity.

See also other guidelines recommendation in the Guidelines section.

Laboratory Studies

See also the Guidelines section for recommendations from the American College of Cardiology, American Heart Association, and other medical societies.

Lipid testing

Lipids can be routinely measured individually as total cholesterol (TC), triglycerides (TGs), or high-density lipoprotein cholesterol (HDL-C). Using these measurements and the Friedewald equation when TG levels are less than 400 mg/dL, low-density lipoprotein cholesterol (LDL-C) can be calculated. Direct LDL measurements allow LDL-C determination on specimens when the TG level is 400 mg/dL or higher and do not require a fasting specimen. However, direct LDL-C measurements have no advantage (and add needless expense) when the TGs levels are below 400 mg/dL.

Children should be on their regular diet for 4-6 weeks before lipid testing. Recent changes in diet that may change lipid levels are an indication to delay testing. Measurements of TC and HDL-C do not need to be performed in the fasting state. However, isolated TG measurements and lipid profile measurements should follow an overnight fast of least 8 hours, preferably 12-14 hours.

Recent severe illness (eg, hospitalization within the last 4-6 wk) is a contraindication to lipid testing because significant stress can also lead to transient decreases in lipid levels or transient lipid abnormalities (eg, hypertriglyceridemia following diabetic ketoacidosis). During acute illness, lipids should not be measured unless hypertriglyceridemia is believed to be the underlying cause of the disease (eg, pancreatitis). Lipoproteins are negative acute phase reactants and their concentrations decline within 24 hours of severe acute stress. In adults, intraindividual variation in TC over the course of one year is reported to be ±8% (range 4%-11%). Intraindividual variation in TG is 13%-41%, whereas HDL-C varies by 4%-12%. Standing TC levels are 8%-12% higher than recumbent values because of a decrease in intravascular fluid that leaks into the interstitial space. The use of anticoagulants in sample tubes may lower TC levels by 3% or less.

Historically, an overnight fast was deemed necessary before lipid screening, but adult data suggest nonfasting lipids may be appropriate for initial screening for cardiovascular risk.[6, 7, 8, 9, 10] A large, cross sectional study was performed in children to assess differences in lipid values based on fasting status.[11] Mora found that although statistically significant differences existed in nonfasting lipid levels, these differences were not clinically significant, with more than 95 percent of children falling into the same classification category whether lipids were fasting or nonfasting.

Non-HDL cholesterol (ie, the TC minus the HDL-C) has been shown to be an excellent measure of risk for cardiovascular disease in adults. Both of the major non-HDL lipoproteins (LDL and very low-density lipoprotein [VLDL]) are the apoprotein-B-containing lipoproteins.

A systematic review of the evidence on benefits and harms of screening adolescents and children for heterozygous familial hypercholesterolemia (FH) indicates that screening in children can detect FH and that lipid-lowering treatment in childhood can lower lipid concentrations in the short term, with little evidence of harm.[12] However, the investigators found no evidence for the effect of childhood screening for FH on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of starting lipid-lowering treatment in childhood.[12]

Guidelines

2018 American College of Cardiology (ACC)/American Heart Association (AHA), and multisocieties [13]

  • In children and adolescents with a family history of either early cardiovascular disease (CVD) or significant hypercholesterolemia, it is reasonable to measure a fasting or nonfasting lipoprotein profile as early as age 2 years to detect familial hypercholesterolemia (FH) or rare forms of hypercholesterolemia.
  • In children and adolescents found to have moderate or severe hypercholesterolemia, it is reasonable to carry out reverse-cascade screening of family members, which includes cholesterol testing for first-, second-, and when possible, third-degree biological relatives, for detection of familial forms of hypercholesterolemia.
  • In children and adolescents with obesity or other metabolic risk factors, it is reasonable to measure a fasting lipid profile to detect lipid disorders as components of the metabolic syndrome.
  • In children and adolescents without cardiovascular risk factors or family history of early CVD, it may be reasonable to measure a fasting lipid profile or nonfasting non-HDL-C once between the ages of 9 and 11 years, and again between the ages of 17 and 21 years, to detect moderate to severe lipid abnormalities.

Normal and abnormal childhood lipid values are outlined below.[13]

TC

  • Acceptable: < 170 mg/dL (< 4.3 mmol/L)
  • Borderline: 170-199 mg/dL (4.3-5.1 mmol/L)
  • Abnormal: ≥200 mg/dL (≥5.1 mmol/L)

LDL-C

  • Acceptable: < 110 mg/dL (< 2.8 mmol/L)
  • Borderline: 110-129 mg/dL (2.8-3.3 mmol/L)
  • Abnormal: ≥130 mg/dL (≥3.4 mmol/L)

HDL-C

  • Acceptable: >45 mg/dL (>1.2 mmol/L)
  • Borderline: 40-45 mg/dL (1.0-1.2 mmol/L)
  • Abnormal: < 40 mg/dL (< 1.0 mmol/L)

TGs

  • Acceptable: (0-9 y) < 75 mg/dL (< 0.8 mmol/L); (10-19 y) < 90 mg/dL (< 1.0 mmol/L)
  • Borderline: (0-9 y) 75-99 mg/dL (0.8-1.1 mmol/L); (10-19 y) 90-129 mg/dL (1.0-1.5 mmol/L)
  • Abnormal: (0-9 y) ≥100 mg/dL (≥1.1 mmol/L); (10-19 y) ≥130 mg/dL (≥1.4 mmol/L)

Non-HDL-C

  • Acceptable: < 120 mg/dL (< 3.1 mmol/L)
  • Borderline: 120-144 mg/dL (3.1-3.7 mmol/L
  • Abnormal: ≥145 mg/dL (≥3.7 mmol/L)

American Association for Clinical Endocrinology

The American Association for Clinical Endocrinology (AACE) included optimal apoprotein-B levels in their 2012 dyslipidemia guidelines.[14]  According to the AACE, for patients at risk for coronary artery disease (CAD), including individuals with diabetes, apoprotein-B levels should be less than 90 mg/dL, whereas patients with established CAD or diabetes who have one or more additional risk factors should have an apoprotein-B level of less than 80 mg/dL. Optimal apoprotein-B levels have not yet been established for children.

The 2017 AACE and American College of Endocrinology guidelines for management of dyslipidemia and prevention of CVD included the following recommendations for children and adolescents[3] :

  • In children at risk for FH (eg, family history of premature CVD or elevated cholesterol), screening should be at age 3 years, again between ages 9 and 11 years, and again at age 18 years.
  • Screen adolescents older than 16 years every 5 years or more frequently if they have atherosclerotic cardiovascular disease (ASCVD) risk factors, have overweight or obesity, have other  elements of the insulin resistance syndrome, or have a family history of premature ASCVD.
  • An LDL-C goal < 100 mg/dL is considered “acceptable” for children and adolescents, with 100 to 129 mg/dL considered “borderline” and 130 mg/dL or greater considered “high”.

National Cholesterol Education Program

The goal of the National Cholesterol Education Program (NCEP) created in 1985 by the National Heart, Lung, and Blood Institute (NHLBI) is to educate both the public and medical professionals about the benefits of lowering cholesterol levels so as to reduce the risk for coronary heart disease. Pediatric guidelines for cholesterol screening are based on a consensus report that is updated periodically.[15, 16, 17, 18]

Abnormalities in lipid levels were initially defined as concentrations at or above the 95th percentile for TC, TGs, and LDL-C for age and sex, whereas low HDL-C concentrations were defined as lower than the 5th percentile for age and sex (see Table 3 below). Many of these cutoffs have been modified by the NCEP to define healthy or desirable levels and not merely levels outside of a certain concentration range defined statistically.

The NCEP has not defined desirable and undesirable TG levels for children and adolescents. For adults, the NCEP has defined desirable TG levels as less than 150 mg/dL, mildly elevated levels as 150-199 mg/dL, elevated levels as 200-499 mg/dL, and levels of 500 mg/dL or higher as very high.

At the University of Florida, hypertriglyceridemia in children is defined as TG levels at or above 125 mg/dL. This value of 125 mg/dL is easy to remember and approximates the mean 95th percentile for TGs in boys and girls across childhood and adolescence. Functionally mild hypertriglyceridemia in children is defined in this clinic as TG levels of 125-299 mg/dL, modest hypertriglyceridemia as TG levels of 300-499 mg/dL, marked hypertriglyceridemia as TG levels of 500-999 mg/dL, and massive hypertriglyceridemia as TG levels of 1000 mg/dL or higher. These cutoffs can be used when determining treatment approaches to hypertriglyceridemia. Desirable and undesirable fasting lipid levels in children and adults are listed in Table 3, below.

Table 3. NCEP Lipid Assessments for Children and Adults (Open Table in a new window)

Children (< 20 y)

Desirable level (mg/dL)

Borderline level (mg/dL)

Undesirable level (mg/dL)

TC

< 170

170-199

≥200

LDL-C

< 110

110-129

≥130

HDL-C*

>45

35-45

< 35

TG†

< 125

...

≥125

Adults (≥20 y)‡

Desirable level (mg/dL)

Borderline level (mg/dL)

Undesirable level (mg/dL)

TC

< 200

200-239

≥240

LDL-C§

< 130

130-159

≥160

HDL-C||

≥40

...

< 40

TGs

< 150

150-199

≥200

* This was not established by NCEP; these values were the adult cutpoints used at the time that the pediatric NCEP guidelines were established.

† This was not established by NCEP; a TG level of 125 mg/dL approximates the mean 95th percentile for TGs in boys and girls during childhood and adolescence.

‡ In March of 2001, cutoff points for desirable and undesirable cholesterol, HDL-C, and other levels were revised in the Adult Treatment Panel III (ATPIII).[18]

§ The optimal LDL-C concentration is less than 100 mg/dL; in patients with cardiovascular disease or diabetes, the optimal LDL-C level is less than 70 mg/dL.

|| If the HDL-C level is 60 mg/dL or higher, one risk factor for coronary heart disease can be subtracted in adults.

 

National Heart, Lung, and Blood Institute

In 2011, the National Heart, Lung, and Blood Institute (NHLBI) released pediatric lipid screening and cardiovascular health recommendations.[19] These guidelines agree with most of those from the NCEP but are more specific, recommending precise ages and more aggressive repeat testing and therapy in high-risk patients. The evidence-based recommendations suggest no routine lipid screening before age 8 years.

In children aged 2-8 years who are considered to be at higher risk (eg, children with a family history of early cardiovascular disease or a parent with a TC level of 240 mg/dL or higher or known dyslipidemia; children with diabetes, hypertension, or a BMI ≥95th percentile; children who smoke cigarettes), fasting lipid profiles should be obtained on two separate occasions and the results averaged. Universal screening is recommended for low-risk individuals at age 9-11 years and again at age 17-21 years.

These recommendations for universal screening, while controversial, recognize the preponderance of evidence that high LDL-C levels are a significant contributor to heart disease, although they do not consider the lack of evidence as to whether the benefits of lifelong treatment with lipid-lowering drugs outweigh the treatment risks.[19]

 

Treatment

Approach Considerations

2018 American College of Cardiology (ACC)/American Heart Association (AHA), and multisociety guidelines

The ACC/AHA and multisociety recommendations for primary prevention of atherosclerotic cardiovascular disease (ASCVD) include the following[13] :

  • ​In children and adolescents with lipid disorders related to obesity, it is recommended to intensify lifestyle therapy, including moderate caloric restriction and regular aerobic physical activity.
  • In children and adolescents with lipid abnormalities, lifestyle counseling is beneficial for lowering low-density lipoprotein cholesterol (LDL-C).
  • In children and adolescents 10 years of age or older with an LDL-C level persistently 190 mg/dL or higher (≥4.9 mmol/L) or 160 mg/dL or higher (4.1 mmol/L) with a clinical presentation consistent with familial hypercholesterolemia (FH) and who do not respond adequately with 3 to 6 months of lifestyle therapy, it is reasonable to initiate statin therapy.

2017 American Association for Clinical Endocrinology (AACE) and American College of Endocrinology (ACE) guidelines

The AACE/ACE guidelines for management of dyslipidemia and prevention of CVD for children and adolescents recommends pharmacotherapy for those older than 10 years who do not respond sufficiently to lifestyle modification, particularly for those satisfying the following criteria[3] : 

  • LDL-C ≥190 mg/dL, or
  • LDL-C ≥160 mg/dL and the presence of two or more cardiovascular risk factors, even after vigorous intervention, or
  • Family history of premature ASCVD (age < 55 y), or
  • Having overweight, obesity, or other elements of the insulin resistance syndrome

Consider the following factors when prescribing low-fat diets for children and adolescents[3] :

  • Total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels are positively correlated in individuals aged 20 years and younger, and low-fat diets that decrease TC levels have also been associated with HDL-C reductions.
  • Increased intake of carbohydrates may increase plasma triglyceride (TG) concentrations in children. High carbohydrate intake is not recommended for children with hypertriglyceridemia.
  • Fish oil supplements have a profound effect on serum TG levels in children. These supplements have been used effectively in young individuals with end-stage renal insufficiency
  • Water-soluble fiber can help improve serum cholesterol levels in children. Studies have shown that both children and adults can achieve cholesterol reductions with high-fiber, low-fat diets
  • Diets supplemented with plant stanols and sterols can reduce LDL-C in children. Studies indicate that both children and adults can achieve LDL-C reduction between 5 and 10% by eating foods that are supplemented with plant stanols and sterols (eg, spreads/ margarines, orange juice, yogurt drinks, cereal bars, and dietary supplements). The AACE concurs with the American Academy of Pediatrics (AAP) and AHA recommendations suggesting that dietary supplementation with plant stanols and sterols may be considered for children with severe hypercholesterolemia or those who are otherwise at high risk. The main safety concern is that plant stanols and sterols may reduce absorption of fat-soluble vitamins and beta-carotene; therefore, the AHA suggests monitoring fat-soluble vitamin status in children receiving supplementation.

Medical Care

Nonpharmacologic management

If a child’s total cholesterol (TC) level is less than 170 mg/dL, no further testing is required for 5 years, when the TC measurement should be repeated. Patients and families should be educated about healthy eating patterns, exercise, and risk-factor reduction. If the TC level is 170-199 mg/dL, TC measurements should be repeated within the next few weeks, and the two results should be averaged.

A fasting lipid profile should be obtained, with calculation of low-density lipoprotein cholesterol (LDL-C), in individuals in whom the TC level is initially at least 200 mg/dL or in whom the average TC level is at least 170 mg/dL. Two lipid profiles should be obtained, and the results should be averaged. If the LDL-C level is below 110 mg/dL and the triglyceride (TG) level is less than 125 mg/dL, no further testing is required for 5 years, when the lipid profile should be repeated. Again, patients and families should be educated about healthy eating patterns, exercise, and risk-factor reduction.

Previously, the recommendation was for the child to first be placed on a step-one diet, which allowed as much as 300 mg of cholesterol and as much as 10% of total fat as saturated fat in the diet. However, guidelines now establish a single dietary recommendation to improve blood lipid levels.

The NHLBI guidelines accepted use of the 2010 Dietary Guidelines for Americans (DGA) and have built on both the DGA and NCEP recommendations to create the CHILD-1 (Cardiovascular Health Integrated Lifestyle Diet–1), a diet consisting of evidence-based recommendations for dietary changes to reduce cardiovascular risk in pediatric patients.[19, 20]

CHILD-1

The CHILD-1 encompasses five different age groups, from birth to age 21 years.[20] Table 4 summarizes these recommendations for each group.

Table 4. Summary of Evidence Based Recommendations for the CHILD-1 (Open Table in a new window)

Age

Dietary Recommendations

Birth to 6 months

  • Infants should be exclusively breastfed until age 6 months

6-12 months

  • Continue breastfeeding until at least 12 months of age (or feed iron-fortified formula if unable to breastfeed), gradually adding solid foods

  • No restriction in fat intake without medical recommendation

  • Water should be encouraged

  • Limit other types of drinks to 100% fruit juice, intake of which should be limited to 4 ounces/day or less

  • No sweetened beverages

12-24 months

  • Switch to reduced fat milk (2% to fat free)

  • Limit or avoid sugar-sweetened drinks

  • Water should be encouraged

  • Transition to table food with total fat content of 30% of daily kcal/estimated energy requirement (EER), saturated fat content of 8-10% of daily kcal/EER, and monounsaturated and polyunsaturated fat content of up to 20% of daily kcal/EER

  • Avoid trans fat as much as possible

  • Total daily cholesterol less than 300 mg

2-10 years

  • Fat-free milk

  • Limit or avoid sugar-sweetened drinks

  • Water should be encouraged

  • Limit total fat to 25-30% of daily kcal/EER, saturated fat to 8-10% of daily kcal/EER, and monounsaturated and polyunsaturated fat to up to 20% of daily kcal/EER

  • Avoid trans fat as much as possible

  • Total daily cholesterol less than 300 mg

  • Encourage high dietary fiber intake from foods

11-21 years

  • Fat-free milk

  • Limit or avoid sugar-sweetened drinks

  • Water should be encouraged

  • Limit total fat to 25-30% of daily kcal/EER, saturated fat to 8-10% of daily kcal/EER, and monounsaturated and polyunsaturated fat to up to 20% of daily kcal/EER

  • Avoid trans fat as much as possible

  • Total daily cholesterol less than 300 mg

  • Encourage high dietary fiber intake from foods

 

CHILD-2

The CHILD-2 is reserved for patients aged 2-21 years with elevated LDL-C, non–HDL-C (non-high-density lipoprotein cholesterol), or triglyceride levels.[19]

Recommendations for patients with elevated LDL-C include the following:

  • Refer to a registered dietician for family medical nutritional therapy

  • 25-30% of calories from fat

  • 7% of calories or less from saturated fat

  • Approximately 10% of calories from monounsaturated fat

  • < 200 mg/day of cholesterol

  • Avoid trans fats as much as possible

Recommendations for patients with elevated TGs or non–HDL-C include the following:

  • Refer to a registered dietician for family medical nutritional therapy

  • 25-30% of calories from fat

  • 7% of calories or less from saturated fat

  • Approximately 10% of calories from monounsaturated fat

  • < 200 mg/day of cholesterol

  • Avoid trans fats as much as possible

  • Decrease sugar intake

  • Increase dietary fish to increase omega-3 fatty acids

Medical management of LDL-C levels of 130 mg/dL or higher

A TG level of 125 mg/dL or less with an average LDL-C level of 130 mg/dL or higher defines a Frederickson type IIA phenotype. National Cholesterol Education Program (NCEP) recommendations for children directly address this phenotype. Dietary measures and exercise should be instituted, and secondary causes should be sought. Ideally, the goal should be to achieve an LDL-C level of less than 110 mg/dL.

The child should engage in regular aerobic exercise. Some patients live in areas that are considered unsafe, and parents limit their children's outdoor activity. Video games, computers, and television viewing have replaced many outdoor activities. Active video games such as Dance Dance Revolution, which uses flashing lights on a dance pad, are now gaining popularity. With advancement in video game consoles, this activity is now available at home or in video arcades. Other ways to increase physical activity include doing chores around the house, such as raking leaves, vacuuming, sweeping, and walking the dog.

Ideal weight should be maintained or achieved. Although weight loss may not be feasible in a growing child, weight maintenance is not an unreasonable goal, so that the child can eventually "grow into" his or her weight. Another approach is to set a goal of lowering the rate of weight gain, in order to bring the child to an appropriate weight at some time in the future (eg, within 1-5 years).

Secondary causes of elevated LDL-C levels should be minimized or eliminated (eg, by treating hypothyroidism or improving glycemic control in diabetes). Laboratory testing should include thyroid studies (free thyroxine [T4], thyroid-stimulating hormone [TSH]), glycated hemoglobin studies (if diabetes is present), liver function tests, and renal function testing (eg, creatinine, BUN [blood urea nitrogen], uric acid and urinalysis).

If TG and LDL-C levels are both elevated (eg, TGs ≥125 mg/dL and LDL-C ≥130 mg/dL), a type IIB phenotype is most commonly present (versus the very rare type III phenotype); the nonpharmacologic treatment of the type IIB phenotype is similar to treatment of the type IIA phenotype.

Type I hyperlipoproteinemia (HLP) treatment

Dietary fat should be restricted to 15% of energy intake. Because medium-chain triglycerides (MCTs) are directly absorbed by the capillaries and because they do not contribute to chylomicron formation, MCT oil can be included in the diet. In infants, Portagen is a formula that is appropriate. Although a strict vegetarian diet may reduce the likelihood of severe hypertriglyceridemia, preventing the potential nutritional deficiencies associated with such a diet is important.

Type IV HLP and type V HLP treatment

With mild elevations in triglycerides (125-299 mg/dL), appropriate interventions include: encouraging a healthy lifestyle; reviewing caloric intake; advising against overeating; encouraging exercise; restricting television, video games, and nonscholastic Internet use to one hour a day or less; avoiding alcohol and estrogen use; and, for all degrees of hypertriglyceridemia associated with obesity, slowing the rate of weight gain or achieving weight loss after growth is complete.

Management of hypoalphalipoproteinemias (low HDL-C levels)

Hypoalphalipoproteinemia is most often observed in association with familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCH), or acquired (insulin-resistant) hypertriglyceridemia. Therapies should therefore target the underlying disorder.

The treatment of acquired hypoalphalipoproteinemias by etiology is as follows:

  • Smoking: Instruct the patient to stop smoking.

  • Obesity: Slow the rate of weight gain in growing children with obesity; weight loss is required after growth has ceased.

  • Hypertriglyceridemia: Lower TG levels through diet, exercise, and weight loss.

  • Renal failure: Dialysis or transplantation is indicated.

  • Androgen administration: Cease androgen administration.

  • Sedentary lifestyle: Instruct the patient to exercise vigorously with aerobic activities for 30-60 minutes daily.

Type IIA HLP and type IIB HLP treatment

When beginning medications, the assumption is that nonpharmacologic measures (as described above) did not achieve an LDL-C level of 160 mg/dL or lower after 6-12 months. Pharmacotherapy should be considered in children older than 10 years with type IIA or type IIB HLP if the following are noted.

An LDL-C level of 160-189 mg/dL and a family history of premature cardiovascular disease or two of the following risk factors:

  • Smoking.

  • Hypertension.

  • HDL-C level of less than 35 mg/dL.

  • Severe obesity (>30% more than ideal body weight).

  • Diabetes mellitus.

  • Physical inactivity.

  • Male sex.

  • Renal disease.

Also, an LDL-C level of 190 mg/dL or higher, regardless of other risk factor status.

 

The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend medical therapy based on family history and risk factors. Positive family history includes myocardial infarction, angina, coronary artery bypass graft/stent/angioplasty, sudden cardiac death in a parent, grandparent, aunt, or uncle that is less than 55 years for males and less than 65 years for females. The risk factors are divided into high and moderate levels.[19]

High-level risk factors include the following[19] :

  • Hypertension that requires drug therapy

  • Cigarette smoking

  • Body mass index (BMI) ≥97th percentile

  • Presence of high-risk condition, such as type 1 diabetes mellitus, type 2 diabetes mellitus, chronic kidney disease, end-stage renal disease, post renal transplant, orthotopic heart transplant, or Kawasaki disease with current aneurysms

Moderate-level risk factors include the following[19] :

  • Hypertension that does not require drug therapy

  • BMI ≥95th percentile, but < 97th percentile

  • HDL-C < 40 mg/dL

  • Presence of a moderate-risk condition, such as Kawasaki disease with regressed coronary aneurysms, chronic inflammatory disease, human immunodeficiency virus (HIV) infection, or nephrotic syndrome

If following the CHILD-2 LDL-lowering recommendations does not reduce the patient's LDL-C to less than 130 mg/dL after 6 months, the following additional recommendations are made[19] :

  • LDL-C ≥190 mg/dL: Initiate statin therapy

  • LDL-C ≥160-189 mg/dL with positive family history or one high-level risk factor or two or more moderate-level risk factors: Initiate statin therapy

  • LDL-C ≥130-159 mg/dL with two high-level risk factors or one high-level risk factor and two or more moderate-level risk factors or clinical cardiovascular disease: Initiate statin therapy

  • LDL-C ≥130-189 mg/dL with negative family history and no other risk factors: Continue the CHILD-2 LDL diet; follow every 6 months with a fasting lipid profile

Guidelines published by the American Heart Association (AHA) in 2006 approach pharmacologic intervention similarly to the NHLBI guidelines by assigning patients to a risk tier based on their disease and also recommending more aggressive targets.[21] The guidelines are as follows:

Tier I (high-risk) factors include the following:

  • Homozygous FH

  • Type 1 diabetes mellitus

  • Chronic kidney disease, end-stage renal disease

  • Heart transplantation

  • Kawasaki disease with coronary aneurysms

Tier II (moderate-risk) factors include the following:

  • FH

  • Kawasaki disease with regressed coronary aneurysms

  • Type 2 diabetes mellitus

  • Chronic inflammatory disease

Tier III (at-risk) factors:

  • Long-term cancer treatment

  • Congenital heart disease

  • Kawasaki disease without detected aneurysms

If a patient has two additional risk factors (eg, including abnormal fasting lipid profile, smoking, family history of early cardiovascular disease, hypertension, elevated BMI, impaired fasting glucose, sedentary lifestyle), they are moved up one risk category. The LDL-C level goal for tier III is < 160 mg/dL, the tier II goal is < 130 mg/dL, and the tier I goal is < 100 mg/dL. Pharmacologic management is recommended in patients aged 10 years and older to achieve these goals.

Statins (3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors)

Statin use has markedly increased in children because these drugs are well tolerated, safe, and efficacious and are now considered first-line therapy.[21] They are approved for use in children as young as age 10 years, and pravastatin is approved for children as young as age 8 years.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate. This is the rate-limiting step in the synthesis of cholesterol. Inhibition of HMG-CoA reductase blocks hepatocyte synthesis of cholesterol. This stimulates the hepatocyte to produce more LDL-Rs. In turn, LDL-R expression on the surface of hepatocytes is increased, which increases LDL clearance from the circulation.

Currently available statins and their doses are shown in Table 5, below. In children, the lowest available dosage form should be used as the starting dose. Dosage increases should be considered every 6-12 weeks until the LDL-C level is less than 130 mg/dL (ideally less than 110 mg/dL) or until the maximum tolerable dose is reached.

After the LDL-C level declines to less than 130 mg/dL, the dose does not need to be further increased.

Table 5. Dosing of HMG-CoA–Reductase Inhibitors (Open Table in a new window)

Generic Name

Adult Dose

Pediatric Dose

Dose Adjustment for Renal Insufficiency or Coadministration with Food or Drugs That Decrease Clearance*

Lovastatin (Mevacor)

Initial: 20 mg/d orally every bedtime

Followed by: 10-80 mg/d orally every bedtime or divided twice daily

10-17 years: 10-20 mg/d orally every bedtime initially; maintenance dosage ranges from 10-40 mg/d

Not to exceed 20 mg/d

Simvastatin (Zocor)

Initial: 5-10 mg/d orally every bedtime

Followed by 5-80 mg/d orally every bedtime or divided twice daily

10-17 years: 10 mg/d orally every bedtime initially; maintenance dosage ranges from 10-40 mg/d

5 mg/d initially; not to exceed 20 mg/d

Pravastatin (Pravachol)

Initial: 10-20 mg/d orally every bedtime

Followed by 5-40 mg/d orally every bedtime

8-13 years: 20 mg orally every day

14-18 years: 40 mg orally every day

Initiate at 5-10 mg/d; not to exceed 20 mg/d (also decrease with hepatic impairment)

Fluvastatin (Lescol)

Initial: 20-30 mg/d orally every bedtime

Followed by 20-80 mg/d orally every bedtime; for 80 mg/d, divide twice daily

10-16 years: 20 mg orally every day initially; maintenance dosage ranges from 20-80 mg/d

No adjustment

Atorvastatin (Lipitor)

Initial: 10 mg/d PO orally every bedtime

Followed by 10-80 mg/d orally every bedtime

10-17 years: 10 mg orally every day initially; maintenance dosages do not exceed 20 mg/d

No adjustment for renal insufficiency; decrease dose or avoid with drugs that decrease clearance

Pitavastatin (Livalo)[22]

Initial: 2 mg/d PO qd

May increase to 4 mg/d

8-17 years: 2 mg PO qd initially; may increase to 4 mg/d

Lower dose with renal impairment, coadministration with erythromycin or rifampin, contraindicated with cyclosporine or active liver disease

Rosuvastatin (Crestor)

10-20 mg orally every day initially; maintenance dosage range is 5-40 mg/d

Not established

5 mg orally every day initially; not to exceed 10 mg/d

* Renal insufficiency is indicated by a creatinine clearance of less than 30 mL/min; agents known to decrease HMG-CoA–reductase inhibitor clearance include grapefruit juice, gemfibrozil, ritonavir, cyclosporine, danazol, amiodarone, azole antifungals, macrolide antibiotics, and verapamil.

Statins have been associated with hepatocellular toxicity and rhabdomyolysis. Frank rhabdomyolysis is rare. The likelihood of rhabdomyolysis increases when a statin is used with cyclosporine, gemfibrozil, erythromycin, azole antifungal agents, niacin, or antiretroviral therapies. The risk also increases with higher doses.

Previously, close monitoring of liver function was recommended, but as of February 28, 2012 the United States Food and Drug Administration (FDA) revised labels for all statins to remove the need for routine periodic monitoring of liver enzymes. The labels now recommend aspartate aminotransferase (AST)/alanine aminotransferase (ALT) should be obtained before starting statin therapy and as clinically indicated thereafter. This change was recommended after the FDA concluded that serious liver injury with statins is rare and unpredictable in individuals and that routine monitoring of liver enzymes did not appear effective in detecting or preventing serious liver injury.

Studies have reported decreases in LDL-C levels of as much as 40% and increases in HDL-C levels of 23%. Increases in ALT, AST, and creatine kinase (CK) levels outside the reference range are reported in most studies to occur in 1-5% of cases. CK screening for myopathy is not recommended. There appears to be no data on the risk of diabetes development in children treated with statins.

Mendelson et al investigated the effectiveness of statins and the effect of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction in a study of 97 children over 3.5 years. The primary outcome was first achieving goal LDL-C, defined as < 130 mg/dL, or < 100 mg/dL with high-level risk factors. The cumulative probability of achieving goal LDL-C within 1 year was 60%; a lower probability of achieving LDL-C goals was associated with higher baseline LDL-C and male sex.[23]

Bile acid–binding resins

The 1991 NCEP recommendations for children advised using bile acid–binding resins as the drugs of choice to treat type IIA HLP in children.[16] However, bile acid–binding resins can lead to elevations in TG levels. Therefore, they are indicated in the treatment of type IIA HLP, but are not routinely indicated for type IIB HLP.

Bile acid–binding resins block bile acid reabsorption from the gut, resulting in bile acid excretion in the stool. Compensatory hepatocyte bile acid synthesis increases, which increases hepatocyte LDL-R expression. Increased LDL-R expression on the hepatocyte surface increases LDL clearance, resulting in a decrease in LDL-C concentrations. Bile acid–binding resins available in the United States include cholestyramine and colestipol.

Cholestyramine and colestipol are insoluble and must be mixed with water or juice to avoid the development of intestinal obstruction. The resins are taken with meals (when bile acids are secreted) and are dosed in scoops or packets of 4-5 g each. Therapy begins with 1-2 packets or scoops per day, given in orange juice or water. The dose is divided between breakfast and dinner and is increased every month to achieve an LDL-C level of less than 130 mg/dL or until maximum dosage is reached (see dosing information below).

Lack of palatability is a major factor limiting their use. The poor palatability may be compounded by the gritty texture of some resin preparations, which can be disguised with a high-pulp juice (eg, pineapple juice). Poor compliance has been reported in more than 50% of patients in some studies. To try to improve compliance, cholestyramine has been packaged into bars (Cholybar) and pills. Again, water must be ingested following the bars or pills to decrease the risk of intestinal obstruction. Reductions in TC and LDL-C levels of 10-40% have been described.

Stein et al observed a significant improvement in LDL-cholesterol from baseline when colesevelam was administered to children aged 10-17 years with heterozygous familial hypercholesterolemia.[24] Additionally, significant improvement was observed for total cholesterol and HDL-cholesterol. The study included patients who were statin-naive or on a stable statin regimen.

The dosing information is summarized below

Cholestyramine (Questran, Questran Lyte, LoCHOLEST, LoCHOLEST Light, Prevalite)

  • One scoop or pouch equals 4 g of cholestyramine.

  • Begin with 1 scoop or pouch mixed with water or juice; advance slowly to 8-16 g/d (usually divided twice daily immediately before major meals; dosage frequency ranges from 1-6 doses/d), not to exceed 24 g/d.

  • The maximal doses refer to adult-sized adolescents.

  • Optimal dosage for children has not been established, but standard texts list a usual pediatric dosage of 240 mg/kg/d divided in 2-3 doses, not to exceed 8 g/d.

  • When calculating pediatric doses of anhydrous cholestyramine resin, 80 mg is contained in 110 mg of Prevalite, 44.4 mg is contained in 100 mg of Questran powder, and 62.7 mg is contained in 100 mg of Questran Light.

Colestipol (Colestid, Flavored Colestid)

  • This agent is available as a 1-g tablet or granules for oral suspension (5 g per packet).

  • For adults, the starting tablet dose is 2 g once or twice daily, with increases of 2 g once or twice daily over periods of 1-2 months.

  • The maximum recommended dose is 16 g/d.

  • The granule starting dose for adults is 5 g orally every day to twice daily.

  • The dose may be increased by 5-g increments every 1-2 months.

  • Depending on the size of the child, these doses need to be reduced by one half to three quarters. Certainly, adult-sized children or adolescents could be dosed as adult levels.

  • The granules are convenient to administer but must not be taken dry. To administer, mix with liquids, soups, cereals, or pulpy fruits (eg, crushed pineapple, pears, peaches).

Use of bile acid–binding resins may lead to a decline in serum folate, carotinoid, and 25-hydroxyvitamin D concentrations. Fat malabsorption may occur. Children treated with bile acid–binding resins should receive supplementation with multivitamins including folate. Approximately 10% of children treated with cholestyramine have elevations in AST levels, lactate dehydrogenase (LD) levels, or both, which is surprising because these agents are not systemically absorbed.

Bile acid–binding resins bind drugs in addition to bile acids and vitamins; therefore, other drugs should be taken at least one hour before or 3 hours after consumption of bile acid–binding resins. No adverse effects on growth have been noted using bile-acid binding resins.

Niacin

Niacin was the second-line drug recommended by the 1991 NCEP panel for treatment of elevated LDL-C concentrations.[16] Niacin is also effective in patients with combined hyperlipidemia (eg, FCH or type IIB HLP) and in patients with isolated hypertriglyceridemia due to elevated VLDL levels. Niacin (ie, nicotinic acid) has been shown to be effective in adults for treating HLP types IIA, IIB, IV, and V. Niacin decreases lipoprotein production and increases lipoprotein clearance. Decrements in LDL-C levels up to 17% have been reported.

Niacin has been associated with toxicities, including liver disease, GI tract upset (abdominal pain, nausea), and facial flushing. In adults, glucose intolerance and hyperuricemia have been reported. Flushing may be minimized by taking aspirin, although this is not an option in prepubertal children because of the risk of Reye syndrome.

In the authors' experience, many children (or their parents) have been unable to endure the facial flushing and GI tract upset produced by niacin. These complications severely limit its use.[25] Although they produce less flushing, extended-release preparations are more likely to produce liver toxicity than immediate-release preparations because higher niacin levels are sustained for longer periods of time. In children, the extended-release agents should only be used with great care and should be used only in exceptional circumstances (eg, homozygous FH).

Few guidelines for niacin dosing in children are available. An effective dose must be balanced against the toxicities. Niacin should be started at a dose of 50 mg/d and very gradually increased (eg, every 4 wk or less often) until the LDL-C level is less than 160 mg/dL when treating HLP type IIA or HLP type IIB, until the TG level is less than 300 mg/dL when treating type IV HLP, or until a dose of 1500-3000 mg/m2 is reached without liver toxicity. Splitting the dose (ie, administering the dose divided twice daily or three times daily) should be attempted as soon as a dose of 100 mg/d of niacin is reached. ALT levels should be measured every 3 months.

With a decline in LDL-C to less than 160 mg/dL or TG levels to less than 300 mg/dL, the dose does not need to be further increased. If the LDL-C level declines to less than 130 mg/dL (in HLP type IIA or IIB) or if the TG level decreases to less than 125 mg/dL (in type IV HLP), the niacin dose can be reduced or a trial period without the medication can be attempted.

Fibric acid derivatives

These drugs inhibit lipoprotein production and increase lipoprotein clearance. Similar to niacin, fibric acid derivatives are useful in treating various dyslipidemias, including HLP types IIA, IIB, IV, and V. Although fibric acid derivatives are effective in adults for the treatment of type IIA phenotypes, the authors do not use fibric acid derivatives in type IIA HLPs because of the effectiveness and safety of statins. The authors reserve the use of fibric acid derivatives for persistent hypertriglyceridemia. Safety and efficacy data on fibric acid derivatives in children are limited.

The table below lists doses and FDA-approved indications in adults. In adults, common toxicities include myalgias, myositis, myopathy, rhabdomyolysis, liver toxicity, gallstones, and glucose intolerance. Gemfibrozil is less likely to cause gallstones than clofibrate (discontinued from the US market). ALT levels should be monitored every 3 months in children treated with gemfibrozil. The authors have only limited experience with fenofibrate but have used gemfibrozil safely and effectively in the clinic.

Table 6. FDA-Approved Uses and Doses of Fibric Acid Derivatives (Open Table in a new window)

Drug Name

Approved Indications

Adult Dose

Gemfibrozil (Lopid)

HLP types IIB, IV, and V

600 mg orally twice daily (ie, 1200 mg total daily dose) 30 min before meals (ie, before breakfast and dinner)

Fenofibrate (Tricor)

HLP types IIA, IIB, IV and V

Initial: 67 mg/d orally; not to exceed 67 mg orally twice daily

Cholesterol absorption blocking agents

Ezetimibe (Zetia) acts on the brush border of the small intestine, inhibiting the absorption of cholesterol. Decreases of as much as 20% in plasma cholesterol may occur. The absorption of vitamin A, D, and E is not affected, and ezetimibe also does not affect adrenocortical steroid hormone production.

Ezetimibe has been produced as a combination pill with simvastatin (Vytorin) in adults. FDA-approved Vytorin is available in preparations that contain 10 mg of ezetimibe and 10, 20, 40 or 80 mg of simvastatin (Zocor). Because both drugs have different mechanisms of action, a synergistic effect causes a 30-60% decrease in cholesterol levels. Compliance is increased because both medicines are included in a single tablet. Limited data in children are available; therefore, widespread use is not yet established.

Other medications

Although aspirin is widely used in adults with atherosclerosis for prevention of atherosclerotic complications (eg, plaque rupture with thrombosis), aspirin should not be used in children, because of the risk of Reye syndrome. Beta carotenes, vitamin C, and folate should be supplied in the diet in amounts to meet recommended daily allowances (RDA). However, pharmacologic doses should not be used, because no current safety or efficacy data are available regarding their use in children for the treatment of dyslipidemia or the prevention of cardiovascular disease.

Fish oils (eg, omega-3 fatty acids) may improve lipid levels, as demonstrated in adult studies, but more evidence is needed in the pediatric population before specific recommendations can be made. In a small, randomized, double-blind, placebo-controlled study (n=20), supplementation with docosahexaenoic acid significantly increased large and buoyant, less atherogenic LDL particles and decreased small and dense, more atherogenic LDL particles.

Adding fiber to the diet is benign and can lower TC and LDL-C levels. Homeopathic medications purported to lower lipids should not be used in pediatric patients, because the safety and efficacy of these agents in children are unknown. Lovaza (omega-3-acid ethyl esters) has been used in children, but no toxicity data has been reported.[26]

Homozygous FH treatment

In the rare patient with homozygous FH, the standard pharmacotherapy is triple therapy consisting of a bile acid–binding resin, a statin, and a fibric acid derivative.

In children aged 10 years and older, biweekly apheresis with plasma exchange for removal of LDL particles is helpful in lowering LDL-C levels. Although invasive and expensive, plasma exchange removes LDL particles, HDL particles, fibrinogen, and platelets.

Liver transplantation is curative but has considerable morbidity and mortality. Suitable liver sources include cadaveric donors and living related donors who lack LDL-R mutations. Parents should not be donors because each parent is heterozygous for an LDL-R mutation. Liver transplantation could be considered when the risk of mortality from the disease exceeds the risk of dying from the liver transplant. However, the success of liver transplantation does pose important ethical controversies in transplantation for homozygous FH.

Whether liver transplantation should be performed in children without clinical evidence of coronary heart disease or whether the surgeon should wait for clinical evidence of coronary heart disease to develop (eg, when the child is potentially a poor candidate for liver transplantation because of coronary heart disease) is controversial. The issue of combined heart-liver transplantation for homozygous FH is another controversial consideration.

Gene therapy for homozygous FH is in its infancy but may offer a potential cure in the future.

Type I HLP treatment

Pharmacotherapy to lower lipids is not indicated for type I HLP. However, in the future, high-dose vitamin antioxidant therapy may have a role in preventing pancreatic inflammation and chronic pancreatitis. In adults with type I HLP, high-dose antioxidants, including vitamin E, have been used in patients with recurrent pancreatitis. No data on the potential use of the oral lipase blocker orlistat (which may lower TG absorption and TG levels) are available.

Type III HLP treatment

Drugs used in adults include niacin and gemfibrozil.

Type IV HLP and type V HLP treatment

Children with a strong family history of premature cardiovascular disease are not infrequently referred to the authors for evaluation and treatment; their predominant laboratory findings include low HDL-C levels and hypertriglyceridemia. When the TG level is 300 mg/dL or higher and HDL-C levels are less than 35 mg/dL with a family history of premature cardiovascular disease, pharmacotherapy (eg, niacin or fibric acid derivatives) is considered based on professional opinion. Treatment suggestions for types IV HLP and type V HLP are outlined below.

  • TG level of 300-499 mg/dL: Encourage a healthy lifestyle and consider pharmacotherapy when HDL-C concentration is less than 35 mg/dL and the patient has a family history of premature cardiovascular or FCH.

  • TG level of 500-999 mg/dL: Encourage a healthy lifestyle and consider pharmacotherapy because of an increased risk of pancreatitis.

  • TG level of 1000 mg/dL or more: Encourage a healthy lifestyle and institute pharmacotherapy because of the increased risk of pancreatitis.

Management of hypoalphalipoproteinemias (low HDL-C levels)

In experimental studies, statins have been used to raise HDL-C levels in the absence of other lipid abnormalities; however, in the authors' opinion, isolated depressions in HDL-C concentrations in the pediatric population should not be treated with drugs.

Summary of treatment recommendations

Statins are the initial drugs of choice for the treatment of type IIA HLP in children. Statins are safe and highly effective. As a result of a lack of adverse effects, compliance is usually high with the use for statins. Lovastatin, simvastatin, atorvastatin, and pravastatin appear to be equally efficacious and safe in children.

Bile acid–binding resins are safe because they are not systemically absorbed and typically do not produce renal toxicity or hepatotoxicity. However, these drugs are not typically palatable; therefore, compliance is usually poor and prevents their widespread and long-term use in children with type IIA HLP. Bile acid–binding resins do not reduce LDL-C levels as effectively as statins do.

Niacin is useful in various phenotypes (eg, HLP types IIA, IIB, or IV), although LDL-C levels are not lowered as effectively as through the use of statins. Flushing and GI tract upset usually interfere with long-term compliance with niacin. In addition, niacin is likely to display hepatotoxicity equal to that of statins.

The primary use of gemfibrozil is in the treatment of HLP types IIA, IIB, IV or V. In adults, this drug is usually safe and effective.

When treating children with type IIA HLP, the authors believe that it is prudent to discuss the advantages and disadvantages of each agent with the patient’s parents. See the diagram summary below.

Pediatric lipid disorders in clinical practice. Ph Pediatric lipid disorders in clinical practice. Pharmacologic approach to the treatment of type IIA hyperlipoproteinemia (HLP).

In patients with type IIB HLP, a statin would be the initial drug of choice. Physicians should avoid the use of bile acid–binding resins in patients with type IIB HLP because resin therapy can worsen hypertriglyceridemia. See the image below.

Pediatric lipid disorders in clinical practice. Ph Pediatric lipid disorders in clinical practice. Pharmacologic approach to the treatment of type IIB hyperlipoproteinemia (HLP).

Treatment of isolated or predominant hypertriglyceridemia (type IV phenotype) is controversial. Niacin is the drug of choice. See the diagram below.

Pediatric lipid disorders in clinical practice. Ph Pediatric lipid disorders in clinical practice. Pharmacologic approach to the treatment of type IV hyperlipoproteinemia (HLP).

Gemfibrozil can be administered if niacin is ineffective or produces unacceptable adverse effects. Because an increasing number of children are recognized as being at risk for premature cardiovascular disease, the authors believe that studies of the safety and efficacy of lipid-lowering drugs in children should be greatly expanded.

 

Guidelines

Cholesterol Management Guidelines

2018 ACC/AHA/multisociety cholesterol management guidelines

The recommendations on management of blood cholesterol were released in November 2018 by the ACC, AHA, and multiple other medical societies.[13, 27]

The guideline's top key recommendations for reducing the risk of atherosclerotic cardiovascular disease through cholesterol management include those summarized below.

Emphasize a heart-healthy lifestyle across the life course of all individuals.

In patients with clinical atherosclerotic cardiovascular disease (ASCVD), reduce low-density lipoprotein cholesterol (LDL-C) levels with high-intensity statin therapy or the maximally tolerated statin therapy.

In individuals with very high-risk ASCVD, use an LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider the addition of nonstatins to statin therapy.

In patients with severe primary hypercholesterolemia (LDL-C level ≥190 mg/dL [≥4.9 mmol/L]), without calculating the 10-year ASCVD risk, begin high-intensity statin therapy.

Assess patient adherence and the percentage response to LDL-C–lowering medications and lifestyle changes with a repeat lipid measurement 4-12 weeks after initiation of statin therapy or dose adjustment; repeat every 3-12 months as needed.

Physical Activity Guidelines

The guidelines on physical activity were released in November 2018 by the Physical Activity Guidelines Advisory Committee of the USDHHS.[28, 29]

Age- and condition-related recommendations

Children aged 3-5 years: Should be physically active throughout the day to enhance growth and development.

Children aged 6-17 years: Sixty minutes or more of moderate-to-vigorous physical activity per day.

Sleep, daily functioning, and mental health

Strong evidence demonstrates that moderate-to-vigorous physical activity improves sleep quality by decreasing the time it takes to fall asleep; it can also increase deep-sleep time and decrease daytime sleepiness.

Single episodes of physical activity promote improvements in executive function, to include organization of daily activities and future planning. Cognition (ie, memory, processing speed, attention, academic performance) also can be improved with physical exercise.

Regular physical activity reduces the risk of clinical depression, as well as reducing depressive symptoms and symptoms of anxiety.

Strong evidence demonstrates regular physical activity improves perceived quality of life.

Risk of diseases and conditions

Regular physical activity minimizes excessive weight gain, helps maintain weight within a healthy range, improves bone health, and prevents obesity, even in children as young as 3-5 years.

In pregnant women, physical activity helps reduce excessive weight gain in pregnancy and helps reduce the risk of developing gestational diabetes and postpartum depression.

Regular physical activity has been shown to improve cognitive function and to reduce the risk of dementia; falls and fall-related injuries; and cancers of the breast, esophagus, colon, bladder, lung, endometrium, kidney, and stomach. It also helps retard the progression of osteoarthritis, type 2 diabetes, and hypertension.

Promotion of physical activity

School- and community-based programs can be effective.

Environmental and policy changes should improve access to physical activity and support of physical activity behavior.

Information and technology should be used to promote physical activity, to include activity monitors (eg, wearable devices), smartphone apps, computer-tailored printed material, and Internet-based programs for self-monitoring, message delivery, and support.

Cardiac Screening in Young Patients

The British Society of Echocardiography and Cardiac Risk in the Young released guidelines in March 2018 aimed at providing guidance for the use of echocardiography in screening young athletes (ages 14–35 years) for inherited and congenital cardiac disease.[30]

Following a detailed questionnaire (including any symptoms or family history) and brief examination, the 12-lead electrocardiogram (ECG) should be the primary investigation. The ECG should be interpreted in accordance with international consensus guidelines. Those with 2 or more borderline ECG findings or any abnormal ECG findings require further investigation.

In the case of an ECG-only screening, transthoracic echocardiography (TTE) is recommended as a second-line investigation in those athletes with an abnormal ECG, cardiovascular symptoms, abnormal physical examination findings, or a family history of sudden death under the age of 40 years.

When screening patients for inherited cardiac disease due to a family history, the referring physician or echocardiographer should establish the patient's level of physical activity. The total volume of training can be defined as (volume = intensity × duration) or Metabolic Equivalent Test (MET-h/week = METS × duration). Low-intensity exercise is defined as corresponding to 1.8–2.9 METS; moderate intensity is defined as corresponding to 3–6 METS; and high intensity is defined as >6 METS.

The aim of the TTE is to differentiate physiologic adaptation from pathologic abnormality where possible.

Sex: Cardiac chamber dimensions in female athletes rarely fall outside of the established normal range. If they do, further investigation is required. It is more common for male athletes to demonstrate a degree of eccentric remodeling of all cardiac chambers.

Age: Highly trained junior athletes still develop cardiac remodeling in response to physiologic conditioning, but this is often at a lower magnitude than in senior athletes.

Ethnicity: Left ventricular (LV) and right ventricular (RV) cavity sizes are similar between African/Afro-Caribbean and white athletes; however, wall thicknesses and left atrial (LA) size are often larger in the African/Afro-Caribbean athlete. Any wall thickness measurement with a value greater than 13 mm in white male athletes (or greater than 11 mm in white female athletes) or greater than 15 mm in African/Afro-Caribbean male athletes (or 13 mm in African/Afro-Caribbean females) requires further investigation.

Body surface area (BSA): The relationship between body size and chamber dimensions is well established, and therefore all chamber dimensions should be indexed for BSA. That aside, cardiac adaptation to exercise involves eccentric hypertrophy beyond what may be attributable to body composition alone. In the extremes of height and weight (BSA >2.3 m2), non-indexed LV wall thickness and diastolic diameter should not exceed 15 mm and 65 mm, respectively.

Symptoms: A positive history including exertional chest pain, syncope or near-syncope, irregular heartbeat or palpitations, shortness of breath or fatigue, and in particular exertional symptoms should direct the echocardiographer to closely assess for potential causes of sudden cardiac death (SCD). Symptoms are non-specific, and therefore it is important to ensure that all possible causes are excluded.

It is important to be aware that exertional chest pain may direct further evaluation for coronary anomalies, while syncope may be related to arrhythmogenic substrate such as arrhythmogenic RV cardiomyopathy (ARVC) or hypertrophic cardiomyopathy (HCM) or to outflow obstruction.

ECG changes: The type of ECG changes that are present on an athlete's ECG will further guide the focus of the examination. For example, T-wave inversion in leads V1–V3 is one of the hallmarks of ARVC and should lead to a more focused assessment of the right heart, whereas inferolateral T-wave inversion is more frequently present in HCM and should prompt a detailed LV assessment.

LV geometry should be determined using a combination of LV mass indexed to BSA (LV mass index; LVMI) and relative wall thickness (RWT). LVMI is calculated as per British Society of Echocardiography guidelines, and RWT is calculated by summating septal and posterior wall thickness in diastole and dividing into the LV diastolic cavity dimension. LV geometry can be reported as normal (normal RWT and normal LVMI), concentric remodeling (increased RWT with normal LVMI), concentric hypertrophy (increased RWT and increased LVMI), or eccentric hypertrophy (normal RWT with increased LVMI) according to published criteria.

 

Questions & Answers

Overview

What is the physiology of lipids and lipoproteins?

What is the Frederickson Classification of dyslipidemias?

What is the pathophysiology of type I hyperlipoproteinemia (HLP)?

What is the pathophysiology of type II hyperlipoproteinemia (HLP)?

What is the pathophysiology of type III hyperlipoproteinemia (HLP)?

What is the pathophysiology of type IV hyperlipoproteinemia (HLP)?

What is the pathophysiology of type V hyperlipoproteinemia (HLP)?

Which conditions are included in the differential diagnoses of a depressed HDL-C level?

DDX

When is an average of two fasting lipid profiles indicated?

What are the pediatric risk factors for cardiovascular disease?

Workup

What are the AACE/ACE guidelines for interpreting pediatric lipid profiles?

What are the ES/ESE/PES guidelines on assessment, treatment and prevention of pediatric obesity?

How is lipid testing performed in children?

What is the role of pediatric lipid testing in the screening for adult cardiovascular risk?

What are the ACC/AHA guidelines on pediatric lipid testing?

What are the AACE guidelines on pediatric lipid testing?

What are the AACE treatment guidelines for dyslipidemia and prevention of CVD?

What is the National Cholesterol Education Program (NCEP)?

What are the NHLBI guidelines on pediatric lipid screening?

Treatment

What are the ACC/AHA guidelines on the primary prevention of atherosclerotic cardiovascular disease (ASCVD) for children and adolescents?

What are the ACC/AHA guidelines AACE/ACE treatment guidelines for dyslipidemia and prevention of CVD for children and adolescents?

What is the initial treatment for pediatric lipid disorders?

What are the CHILD-1 (Cardiovascular Health Integrated Lifestyle Diet–1) recommendations?

What are the CHILD-2 (Cardiovascular Health Integrated Lifestyle Diet–1) recommendations?

How are pediatric LDL-C levels of 130 mg/dL or higher treated?

How is type I hyperlipoproteinemia (HLP) treated?

How are types IV and V hyperlipoproteinemia (HLP) treated?

How are pediatric hypoalphalipoproteinemia (low HDL-C levels) treated?

How are types IIA and IIB hyperlipoproteinemia (HLP) treated?

What are the NHLBI guidelines on the treatment of type II hyperlipoproteinemia (HLP)?

What are the AHA guidelines on the treatment of type II hyperlipoproteinemia (HLP)?

What is the role of statins in the treatment of pediatric lipid disorders?

What is the role of bile acid-binding resins in the treatment of pediatric lipid disorders?

What is the role of niacin in the treatment of pediatric lipid disorders?

What is the role of fibric acid derivatives in the treatment of pediatric lipid disorders?

What is the role of ezetimibe (Zetia) in the treatment of pediatric lipid disorders?

What is the role of aspirin in the treatment of pediatric lipid disorders?

What is the role of fish oils in the treatment of pediatric lipid disorders?

What is the role of dietary fiber in the treatment of pediatric lipid disorders?

How is homozygous FH treated?

What is the role of medications in the treatment of type I hyperlipoproteinemia (HLP)?

What is the role of medications in the treatment of type III hyperlipoproteinemia (HLP)?

What is the role of medications in the treatment of types IV and V hyperlipoproteinemia (HLP)?

What is the role of medications in the treatment of pediatric hypoalphalipoproteinemia (low HDL-C levels)?

Which medications are used in the treatment of pediatric lipid disorders?

Guidelines

What are the ACC/AHA cholesterol management guidelines for children and adolescents?

Which organization has released guidelines on physical activity for children and adolescents?

What are the USDHHS guidelines on physical activity for children and adolescents?

How does physical activity affect sleep in children and adolescents?

How does physical activity affect disease risk in children and adolescents?

What are effective ways to promote physical activity in children and adolescents?

What are the British Society of Echocardiography and Cardiac Risk in the Young guidelines on cardiac screening for young athletes?