Pediatric Lipid Disorders in Clinical Practice Treatment & Management

Nonpharmacologic management

If a child’s 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 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 2 results should be averaged.

A fasting lipid profile should be obtained, with calculation of 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 less than 110 mg/dL and the TG level is less than 125 mg/dL, no further testing is required for 5 years, when the lipid profile should be repeated. Patients and families should always be educated about healthy eating patterns and risk factor reduction. If the LDL-C level is 110-129 mg/dL, an NCEP diet is prescribed, and the child is reevaluated in one year.

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, new guidelines now establish a single dietary recommendation to improve blood lipid levels.

The fundamentals of the lipid-lowering diet include the following:^[6]

• Less than 30% total fat and less than 7% saturated fat in the diet
• Less than 200 mg of cholesterol per day (or 100 mg/1000 kcal in the diet)
• Carbohydrates composing approximately 55% of total energy intake
• Protein composing approximately 15-20% of total energy intake

The diet should also include highly complex carbohydrates and little refined carbohydrates. Fad diets (eg, Atkins diet and South Beach diet) should be avoided. The NCEP diet is safe and does not interfere with growth. A quick way to estimate energy requirements in children is to provide a base of 1000 kcal per day and add 100 kcal per year of age to calculate total daily energy need. For example, a 10-year-old child should ingest approximately 2000 kcal per day (1000-kcal/d base + [(age in y) X 100 kcal/d]). If an estimated maximum of 30% of the diet is fat, the fat intake should not exceed approximately 600 kcal per day.

Fat provides 9 kcal/g; however, if this figure is rounded to 10 kcal/g, 600 kcal of fat equals approximately 60 g of fat per day. By placing a numerical value on the amount of fat that the child eats per day (eg, approximately 60 g maximum) and by knowing the number of grams of fat in particular food servings, dietary fat intake can theoretically be regulated if the child adheres to a specific diet. For example, a popular double-patty fast-food cheeseburger contains approximately 34 g of fat; however, choosing a chicken breast sandwich from the same fast food menu supplies only 6 g of fat.

Children should be reevaluated in 6 months to assess their progress and should be allowed one year to achieve their lipid goal. The goal of dietary intervention is to achieve an LDL-C level of 110 mg/dL or less.

Management of LDL-C levels of 130 mg/dL or higher

A TG level 125 mg/dL or less with an average LDL-C level of 130 mg/dL or higher defines a type IIA Frederickson phenotype. 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 lower than 110 mg/dL (at least 130 mg/dL or lower).

The child should engage in regular aerobic exercise. Some patients live in areas that are considered unsafe, and parents limit their 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 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 may eventually grow into the weight. Another approach is to set a goal of lowering the rate of weight gain, which is designed to bring the child into line with an appropriate weight at some time in the future (eg, 1-5 y).

Secondary causes of elevated LDL-C levels should be eliminated or minimized, such as treating hypothyroidism or improving glycemic control in diabetes. The laboratory testing should include thyroid studies (Free T4, thyroid-stimulating hormone [TSH]), glycosylated hemoglobin studies (if diabetic), liver function tests, and a renal profile.

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 present; the nonpharmacologic treatment in patients with the type IIB phenotype is similar to treatment in those with the type IIA phenotype.

Type I HLP treatment

Dietary fat should be restricted to 15% of energy intake. This usually controls symptoms, reducing triglyceride levels to lower than 1000 mg/dL. 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.

Types 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 an 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 FH, 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 is noted:

• LDL-C level of 160-189 mg/dL and a family history of premature cardiovascular disease or 2 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
• LDL-C level higher than 190 mg/dL, regardless of other risk factor status

The 2008 AAP Guidelines again offer more aggressive LDL goals and age of recommended treatment.^[3] Pharmacologic management should be considered in patients aged 8 years or older with an LDL-C level of 190 mg/dL or more, 160 mg/dL or more with a family history of early cardiovascular disease or 2 or more additional risk factors (as stated above), or 130 mg/dL or more in a patient with diabetes mellitus.

The goal of therapy should be an LDL-C level of less than 160 mg/dL initially, but more aggressive targets such as levels less than 130 mg/dL, or even 110 mg/dL, should be considered for patients with a strong family history of early cardiovascular disease, diabetes mellitus, metabolic syndrome, and obesity. The difference in age recommendation is likely secondary to the US Food and Drug Administration (FDA) approval of pravastatin (Pravachol) in patients aged 8 years and older after the NCEP guidelines were initially published and since updated.

Guidelines published by the AHA in 2006 approach pharmacologic intervention differently than the other guidelines by assigning patients to a risk tier based on their disease and also recommend more aggressive targets.^[10]

The guidelines are as follows:

• Tier I (high risk)

  • Homozygous FH
  • Type 1 diabetes mellitus
  • Chronic kidney disease, end-stage renal disease
  • Heart transplantation
  • Kawasaki disease with coronary aneurysms
• Tier II (moderate risk)

  • FH
  • Kawasaki disease with regressed coronary aneurysms
  • Type 2 diabetes mellitus
  • Chronic inflammatory disease
• Tier III (at risk)

  • Long-term cancer treatment
  • Congenital heart disease
  • Kawasaki disease without detected aneurysms

If a patient has 2 additional risk factors (eg, including abnormal fasting lipid profile, smoking, family history of early cardiovascular disease, hypertension, elevated body mass index [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.

Bile acid–binding resins

The 1991 NCEP recommendations advise using bile acid–binding resins as the drugs of choice to treat type IIA HLP in children.^[5] 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 in at least 2-6 ounces of water 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 risk of intestinal obstruction. Reductions in TC and LDL-C levels from 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.^[11] 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 as follows:

• 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/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 aspartate aminotransferase (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.^[5] 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.^[12] 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. Alanine aminotransferase (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.

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

In the past, statins were considered if neither bile acid sequestrants nor niacin were effective or if the drugs were not tolerated. Statin use has markedly increased in children because these drugs are well tolerated, safe, and efficacious. Statins are now approved for use in children as young as 10 years old (pravastatin is approved for children as young as 8 y) and are more commonly being used as first-line therapy.

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 4, 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 160 mg/dL or until the maximum tolerable dose is reached.

After the LDL-C level declines to less than 160 mg/dL, the dose does not need to be further increased. If the LDL-C level declines to less than 130 mg/dL, the statin dose can be reduced or a trial period off medication can be attempted. The LDL-C goals in children treated for hypercholesterolemia are not yet as aggressive as they are in adults.

Table 4. Dosing of HMG-CoA–Reductase Inhibitors (Open Table in a new window)

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. For all statins except pravastatin and rosuvastatin, AST/ALT monitoring should be undertaken before therapy, after 6 weeks, 12 weeks, and every 6 months. For pravastatin and rosuvastatin, monitoring is recommended before therapy, after 12 weeks, and 12 weeks after dosage changes.

Studies have reported decreases in LDL-C levels of as much as 40% and increases in HDL of 23%. Increases in ALT, AST, and creatine kinase levels outside the reference range are reported in most studies to occur in 1-5% of cases.

US Food and Drug Administration (FDA)-approved indications for use of statins are outlined as follows:

• Lovastatin (Mevacor) - HLP types IIA and IIB, primary and secondary prevention of coronary heart disease, and adolescents with heterozygous FH
• Simvastatin (Zocor) - HLP types IIA, IIB, III, and IV; secondary prevention of coronary heart disease; adolescents with heterozygous FH; and homozygous FH
• Pravastatin (Pravachol) - HLP types IIA, IIB, III, and IV; primary and secondary prevention of coronary heart disease; and adolescents with heterozygous FH
• Fluvastatin (Lescol) - HLP types IIA and IIB, secondary prevention of coronary heart disease, and adolescents with heterozygous FH
• Atorvastatin (Lipitor) - HLP types IIA, IIB, III, and IV; primary prevention of coronary heart disease; adolescents with heterozygous FH, and homozygous FH
• Rosuvastatin (Crestor) - HLP types IIA, IIB, and IV and homozygous FH; not approved for children

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

Cholesterol-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 or for prevention of atherosclerosis, 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 for their use in children in the treatment of dyslipidemia or prevention of cardiovascular disease are available.

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 children because the safety and efficacy of these agents in children is unknown.

Homozygous FH treatment

In the rare patient with homozygous FH, the standard pharmacotherapy is triple therapy, which consists 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.

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

Bile acid–binding resins are the initial drugs of choice for the treatment of type IIA HLP 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. Statins are safe and highly effective. As a result of a lack of adverse effects, compliance is usually high with the use for 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 their parents. See the diagram summary below.

If the parent rejects bile acid–binding resins as first-line therapy for their child, the physician can offer niacin therapy. Niacin can also be offered if the child or parent accepts a trial of a bile acid–binding resin but compliance is poor or the LDL-C response is inadequate (eg, the LDL-C level remains ≥ 160 mg/dL) or the decline in LDL-C levels is only marginal (eg, the LDL-C declines < 15-20%).

Similar to bile acid–binding resins, a statin should be offered if compliance is poor with use of niacin, if the LDL-C response is inadequate (ie, the LDL-C level is ≥ 160 mg/dL), or if the decline in LDL-C is only marginal (eg, < 15-20% decline in LDL-C level). Lovastatin, simvastatin, atorvastatin, and pravastatin appear to be equally efficacious and safe in children.

In patients with type IIB HLP, niacin is 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. If niacin is ineffective or produces unacceptable adverse effects, either gemfibrozil or statin can be used, as shown in the diagram below.

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

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.

Patients and families should be educated about healthy eating patterns and risk-factor reduction.

If the LDL-C level is 110-129 mg/dL, an NCEP diet is prescribed, and the child is reevaluated in one year.

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, new guidelines now establish a single dietary recommendation to improve blood lipid levels.

The fundamentals of the lipid-lowering diet include the following:^[6]

• Less than 30% total fat and less than 7% saturated fat in the diet
• Less than 200 mg of cholesterol per day (or 100 mg/1000 kcal in the diet)
• Carbohydrates composing approximately 55% of total energy intake
• Protein composing approximately 15-20% of total energy intake

The diet should also include highly complex carbohydrates and little refined carbohydrates. Fad diets (eg, Atkins diet and South Beach diet) should be avoided. The NCEP diet is safe and does not interfere with growth.

See Medical Care for more guidelines.

The child should engage in regular aerobic exercise. Some patients live in areas that are considered unsafe, and parents limit their 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 chores around the house, such as raking leaves, vacuuming, sweeping, and walking the dog.