OVERVIEW: What every practitioner needs to know

Are you sure your patient has dyslipidemia? What are the typical findings for this disease?

Dyslipidemia can take many forms in childhood, including genetic dyslipidemia; dyslipidemias due to renal, kidney disease, or diabetes; dyslipidemia due to certain drugs; or dyslipidemia due to lifestyle issues such as obesity, diet, and physical activity. The main concern with dyslipidemia is that it increases the risk of cardiovascular disease (myocardial infarction and stroke) in adulthood. Autopsy studies and studies using noninvasive imaging have shown that elevated low-density lipoprotein C (LDL-C) in adolescents is associated with atherosclerotic lesions. Lesions are even more prevalent and more pronounced when other risk factors such as obesity and hypertension are also present.

There are few symptoms related to dyslipidemia in childhood. The exception is the homozygous form of familial hypercholesterolemia. In this genetic disease, the patient may experience planar xanthomas, tendinous xanthomas in the Achilles tendon, and corneal arcus. Because of the skin manifestations, homozygous familial hypercholesterolemia is often first diagnosed by a pediatric dermatologist.

Diseases that mimic dyslipidemia

There are few, if any, diseases that mimic dyslipidemia. However, the dyslipidemia that goes with hypothyroidism is sometimes the first finding leading to the diagnosis.

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What caused this disease to develop at this time?

The most severe dyslipidemias are genetic. The homozygous form of familial hypercholesterolemia occurs in 1/1,000,000 births. The heterozygous form occurs in 1/300-1/500 births. These genetic defects of the LDL-C receptor result in substantial elevation of LDL cholesterol levels. This abnormality is caused by any of a number of genetic mutations that adversely affect the LDL-C receptor. A number of mutations have been described, some of which result in dysfunction of the LDL-C receptor and others, such as the PCSK9 defect, result in gain of function in the process that metabolizes and disposes of LDL-C receptors.

Another important form of genetic dyslipidemia is familial combined dyslipidemia. In this abnormality, LDL-C levels are often elevated (although not as elevated as in heterozygous familial hypercholesterolemia with elevation of triglyceride levels. HDL-C levels are often reduced in this disorder. The specific genetic cause is not known. The frequency of familial combined dyslipidemia is reported to be 1/100-1/200 individuals.

Usually, the cause of the more severe form of dyslipidemia is a combination of genetics and environmental factors, such as a high-saturated-fat, high-cholesterol diet.

Atherogenic dyslipidemia is a result of obesity and insulin resistance. It consists of elevated triglyceride and low HDL-C levels. This form of dyslipidemia is often present in adults with metabolic syndrome. Although there is no widely accepted definition of metabolic syndrome in pediatrics, it is clear that children and adolescents can have the clustered features of metabolic syndrome, including obesity, central obesity (increased waist circumference), elevated blood pressure, insulin resistance, elevated triglyceride levels, and low HDL-C levels.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The approach to diagnosis is by lipid screening. Historically, a family history–based approach to screening has been used. However, this has been shown to miss many children with elevated LDL-C levels. The currently recommended approach is that all children should have lipid screening between the ages of 9 and 11 years. This is the age at which lipid concentrations are most predictive of adult values. It avoids the decrease in LDL-C levels (10%-20%) often seen during puberty. It is also the age at which the atherosclerotic process begins to develop more aggressively.

Screening can occur with a nonfasting non–HDL-C determination, which is calculated by subtracting the HDL-C from the total cholesterol, or a with a fasting lipid profile. If the nonfasting non–HDL-C level is elevated, a fasting lipid profile should be obtained to confirm the result (Table I).

Table I.
Acceptable Borderline High High
Total Cholesterol <170 170-199 ≥200
LDL Cholesterol <110 110-129 ≥130
Non-HDL Cholesterol <120 120-144 ≥145

HDL = high-density lipoprotein; LDL = low-density lipoprotein

Would imaging studies be helpful? If so, which ones?

In general, imaging studies are not useful. Ultrasonographic studies of the carotid artery can be used to measure carotid intima media thickness, which is a measure of the atherosclerotic process. These studies remain in the realm of research and are not used routinely in the clinical setting.

Confirming the diagnosis

The algorithm in Figure 1 depicts the recommended approach to management of elevated LDL-C levels. The aggressiveness of the approach is based on the age of the child, the level of LDL-C, and the presence of other risk factors for cardiovascular disease.

Figure 1.

Management dyslipidemia when LDL-C is elevated

If you are able to confirm that the patient has dyslipidemia, what treatment should be initiated?

The first approach to treatment of dyslipidemia is lifestyle modification. This includes changes in diet and physical activity.

Population Diet (age 12 months and older): Saturated fat should be less than 10% of calories. Cholesterol should be less than 300 mg/day. A more advanced diet would require saturated fat to be less than 7% of calories and cholesterol less than 200 mg/day. This dietary approach is best achieved by increased intake of fruits, vegetables, whole grains, low-fat dairy products, and lean meats such as poultry (without skin) and fish. Sugar-sweetened beverages and processed foods should be decreased. Increased fiber intake and the addition of products with plant sterols or stanols can be beneficial adjuncts to diet modification.

Physical Activity: Sixty minutes of moderate to vigorous physical activity per day. It is also recommended that children and adolescents spend less than 2 hours per day of sedentary time.

Pharmacologic Treatment (elevated LDL-C level): When indicated (see Figure 1), pharmacologic treatment can dramatically improve lipid levels.

Statins are preferred for initial pharmacologic treatment for children 8 years of age and older.

Other medication classes are also available, including bile acid sequestrant agents and cholesterol absorption blockers. In special cases, such as with homozygous familial hypercholesterolemia, aggressive pharmacologic intervention should begin before the age of 8 years. In these patients, LDL apheresis may be required to achieve acceptable levels.

The treatment goal is to achieve LDL-C levels less than 130 mg/dL or at least a 50% reduction in these levels. However, increased doses of medication lead to increased risk of side effects. It is important to consider the balance between achieving goal and potential side effects.

Treatment for Homozygous Familial Hypercholesterolemia

Initiate therapy early in life.

High-dose statins in addition to other medications are usually needed.

Plasma (LDL) apheresis is often required.

Liver transplantation is used in some centers.

Treatment for Elevated Triglyceride Levels

The mainstay of treatment is diet modification. A low-saturated-fat, low-carbohydrate diet is required. Children with elevated triglyceride levels are often overweight, so weight managment is important.

The addition of fish oil (omega 3 fatty acids) can be a beneficial adjunct to diet change.

Pharmacologic treatment for elevated triglyceride levels is usually not considered until levels are greater than 500 mg/dL. Fibrate medications are used for very elevated triglyceride levels but have not been extensively studied in children and adolescents.

What are the adverse effects associated with each treatment option?

Diet: There are few, if any, adverse effects of lowering saturated fat and cholesterol in the diet.

Statins:Myopathy, rhabdomyolysis—these conditions are uncommon and can be monitored by following symptoms of muscle aches, pains, cramps, and weakness and with measurement of blood creatine kinase levels

Elevations of hepatic transaminase levels—these are usually transient and rarely severe enough (>3 times upper limit of normal) to require discontinuation of the medication

Teratogenicity—these medications should be used with caution in adolescent girls who may become pregnant

Bile acid sequestrants:

Adverse effects are limited to the gastrointestinal tract and include constipation, gas, bloating and cramps

Cholesterol absorption inhibitors:

Gastrointestinal cramps, dyspepsia




Gastrointestinal constipation, dyspepsia


Myopathy—these drugs used in combination with statins may increase the risk of myositis and rhabdomyolysis

Omega 3 fatty acids/fish oil:




What are the possible outcomes of dyslipidemias?

The outcomes of dyslipidemia are generally long-term outcomes. Treatment of dyslipidemia is designed to lower the lifetime risk of cardiovascular disease, which is the leading cause of death and disability in adults.

Untreated heterozygous familial hypercholesterolemia increases the risk of cardiovascular disease events related to atherosclerosis. With untreated heterozygous familial hypercholesterolemia, 25% of female patients and 50% of male patients will have clinically apparent cardiovascular disease by age 50 years.

Untreated homozygous familial hypercholesterolemia results in even more aggressive atherosclerosis. Patients with homogygous familial hypercholesterolemia will often experience clinically apparent atherosclerotic cardiovascular disease by their teenage years and often die of heart disease in their late teenaged years or early 20s. Patients with homozygous familial hypercholesterolemia can also acquire aortic valve stenosis.

What is the evidence?

Berenson, GS, Srinivasan, SR, Bao, W. “Bogalusa Heart Study. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults”. N Engl J Med. vol. 338. 1998. pp. 1650-6. (This is a study of children who had participated in the Bogalusa Heart Study in which they had risk factors for future cardiovascular disease measured in school. The cohort was followed over time and autopsies were performed on those who died of accidental causes. Childhood risk factors were correlated with the extent of atherosclerosis in the coronary arteries and the aorta. Autopsies were performed in 204 young people aged 2-39 years. The extent of fatty streaks and fibrous plaques increased with age and with risk factors such as obesity, dyslipidemia, hypertension, and cigarette smoking. As the number of risk factors increased in childhood, so did the severity of atherosclerosis. These results emphasize that atherosclerosis begins in childhood, is related to traditional risk factors, including dyslipidemia (high LDL-C and low HDL-C levels), and that clustering of multiple risk factors is particularly important.)

Ritchie, SK, Murphy, ECS, Ice, C. “Universal versus targeted blood cholesterol screening among youth: The CARDIAC Project”. Pediatrics. vol. 126. 2010. pp. 260-5. (This study was designed to evaluate the sensitivity and specificity of family history in identifying children with severe or genetic dyslipidemias. The study included 20,266 fifth graders in West Virginia; 71.4% of children met the National Cholesterol Education Program's definition for targeted screening based on a positive family history or the presence of other risk factors. Of the 28.6% who did not have a family history, 548 (9.5%) had dyslipidemia, and 1.7% warranted pharmacologic treatment. These results demonstrate that a targeted approach to lipid screening will miss children with dyslipidemia and suggests that universal screening may be more appropriate.)

Stein, EA, Marais, AD, Szamosi, T. “Colesevelam hydrochloride: efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia”. J Pediatr. vol. 156. 2010. pp. 231-6. (This is the report on a clinical trial designed to evaluate the safety and efficacy of colesevelam, which is a bile acid sequestering agent. One hundred ninety-four children aged 10-17 years were randomly assigned to receive colesevelam or a placebo. At week 8, a significant difference from baseline LDL-C levels was found for colesevelam compared with the placebo. There were few adverse effects, and adherence to the treatment was good. These results indicate that colesevelam is a reasonable choice for treatment of dyslipidemia in children.)

Daniels, SR, Gidding, SS, de Ferranti, SD. “Pediatric aspects of familial hypercholesterolemias: recommendations from the National Lipid Associate Expert Panel on Familial Hypercholesterolemia”. J Clin Lipidol. 2011. pp. 530-7. (This review statement from the National Lipid Association evaluates approaches to screening and management of familial hypercholesterolemia in children. Recommendations are made for universal screening of children for lipid abnormalities between the ages of 9-11 years. Screening can be performed using either a fasting lipid profile or a nonfasting non-HDL cholesterol profile. Further recommendations are provided regarding the treatment of dyslipidemia. The first focus is on changing diet and other lifestyle factors. it is also recommended that attention be given to other risk factors, such as obesity, hypertension, diabetes mellitus, and cigarette smoking. In addition, the report outlines the use of pharmacologic agents when needed.)

McCrindle, BW, Urbina, EM, Dennison, BA. “American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee; American Heart Association Council of Cardiovascular Disease in the Young; American Heart Association Council on Cardiovascular Nursing. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing”. Circulation. vol. 115. 2007. pp. 1948-67. (This paper presents a review of pharmacologic intervention for the treatment of dyslipidemia. It also emphasizes that pharmacologic treatment is reserved for children aged 10 years and older with severe dyslipidemia, usually the result of a genetic abnormality. It also indicates that pharmacologic treatment should be instituted only after therapy with diet and other lifestyle factors have failed to achieve target lipid and lipoprotein levels. The results of this review support the use of statin medications as a first-line drug therapy for genetic dyslipidemia in children.)