The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, including in Korea [
Increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and decreased high-density lipoprotein cholesterol (HDL-C) are well-known risk factors associated with CVD [
Dyslipidemia is closely related to other CVD risk factors, such as hypertension, obesity, and smoking status, not only in adults but also in children and adolescents [
Although CVD does not usually develop until the fourth decade of life, it is well known that atherosclerosis begins in childhood [
Among Korean children and adolescents aged 10–19 years, 20% had at least one type of dyslipidemia [
Early recognition of and intervention for dyslipidemia in Korean children and adolescents is important for preventing CVD later in life. In this context, the Committee on Pediatric Dyslipidemia of the Korean Society of Pediatric Endocrinology (KSPE) has recently developed evidence-based clinical practice guidelines to treat dyslipidemia in Korean children and adolescents.
Several studies, such as the Lipid Research Clinics Prevalence Study and the National Health and Nutrition Examination Survey, have shown that there are sexual, racial, and ethnic differences in lipid profiles and also in the overall prevalence of dyslipidemia [
The Committee of Clinical Practice Guidelines of the KSPE decided to adopt the National Heart Lung and Blood Institute (NHBLI) 2011 guidelines for dyslipidemia to prevent adulthood CVD by lifestyle modification or medical intervention [
There have been controversies in the optimum TG cutoff level. Because carbohydrates make up a major part of the Korean traditional diet, some researchers have insisted that a higher TG concentration of 150 mg/dL, which corresponds to the 90th percentile of Korean adolescents, is more appropriate in defining dyslipidemia [
According to the cutoff points of the NHBLI guidelines, 19.7% of Korean children and adolescents from 10–18 years of age had at least one abnormal lipid concentration [
Screening for lipids in children is based on the rationale that early identification and control of pediatric dyslipidemia will reduce the risk and severity of CVD in adulthood. Therefore, the Committee of Clinical Practice Guidelines of KSPE recommends "universal screening." Universal screening in this guideline might be performed to detect those with undiagnosed heterozygous familial hypercholesterolemia who would require more intensive treatment, possibly including pharmacological therapy [
Universal lipid screening should be performed with the measurement of nonfasting non-HDL-C in all children aged 9–11 and 17–21 years. Non-HDL-C is calculated as follows: non-HDL-C=TC–HDL-C. Non-HDL-C includes all cholesterol types present in lipoprotein particles (LDL-C, lipoprotein(a), intermediate density lipoprotein, and very-low-density lipoprotein) that are considered atherogenic. Therefore, non-HDL-C is a better independent predictor of CVD than LDL-C and is also as good a predictor of future adulthood dyslipidemia that can replace LDL-C [
Screening for dyslipidemia is not recommended until 2 years of age. For children aged 2–8 and 12–16 years, routine lipid screening is also not recommended. Targeted screening is only encouraged if there is a family history of high cardiovascular risk or other risk factors and conditions. The risk factors and conditions to consider for the screening and treatment decisions in children with dyslipidemia are included in
Rising rates of dyslipidemia in Korean children and adolescents might be due to increases in adoption of the western lifestyle, especially the westernized diet and decrease in physical activity [
The KSPE guidelines recommend that all children and adolescents engage in moderate-to-vigorous physical activity for at least 1 hour a day and limit sedentary activity, including television, internet, and video games, to <2 hours a day. Cigarette exposure also should be strongly discouraged. In addition, all children and adolescents should try to attain an ideal body weight (body mass index ≤85th percentile for age and sex).
Any diet change must provide optimal nutrition for growth and development. The 2010 Dietary Guidelines for Americans recommend the Cardiovascular Health Integrated Lifestyle Diet (CHILD-1) be used in children and adolescents 2 years of age or older who are at risk for CVD [
Exclusively breastfeeding should be done until 6 months of age. If direct breastfeeding is impossible, use a breast pump, and if any breastfeeding is not available, iron-fortified infant formula should be fed. Breastfeeding should continue for at least 12 months while gradually adding solids. If breast milk decreases, feed iron-fortified formula until 12months. Infants under 12 months of age should not limit their fat intake without medical indication and limit 100% juice to about 120 mL per day, drink water without any other beverages.
Consult health-care provider about low-fat milk intake after 12 months of age if a family history of obesity, heart disease, or dyslipidemia is present [
If the fasting lipid profile findings exceed the therapeutic goals after a 3-month trial of the CHILD-1 diet, then the CHILD-2-LDL, or CHILD-2-TG diet should be recommended based on specific abnormal lipid parameters.
The detailed contents of each diet are listed in
Decisions regarding the need for drug therapy should be based on the average values from at least 2 fasting lipid tests obtained at least 2 weeks but no more than 3 months apart.
Drug therapy is recommended in children ≥10 years with a poor response to diet and lifestyle therapy for at least 6–12 months [
Children with average LDL-C levels≥250 mg/dL or TG≥ 500 mg/dL should be referred directly to a lipid specialist. If the TG concentration is >500 mg/dL, there is a risk of pancreatitis, and specialist consultation is therefore necessary [
Statin treatment is generally not started in children under the age of 10, and it is limited to patients homozygous for familial hypercholesterolemia or with LDL-C≥400 mg/dL, primary hypertriglyceridemia≥500 mg/dL, CVD, or cardiac transplantation.
If the LDL-C remains ≥190 mg/dL after a 6-month trial of lifestyle management (CHILD-1→CHILD-2-LDL) for children aged 10 years and older, statin therapy should be considered [
In children who are at least 10 years of age, the administration of statins, fibrates, or niacin may be considered if the LDL-C has reached its target but the non-HDL-C remains ≥145 mg/dL [
When TG improves with weight control and lifestyle changes in children with hypertriglyceridemia, medication therapy is unnecessary. As a supportive medical therapy, the use of omega-3 fatty acids is suggested along with lifestyle modification via the CHILD-2-TG, especially in children with hypertriglyceridemia. When the affected child has TG levels from 200–499 mg/dL and a non-HDL-C result ≥ 145 mg/dL, omega-3 fatty acid treatment may be considered [
However, safety issues remain unclear due to the limited experience with omega-3 fatty acids in children, which have only been used in a small number of cases [
Statins and bile acid-binding resins are the two main classes of medications currently used to treat this condition in pediatric patients. Commonly used medications are listed in
A statin is recommended as the initial medication of choice for children with elevated LDL-C or non-HDL-C levels. Statins inhibit the rate-limiting enzyme β-hydroxy β-methylglutaryl-CoA reductase and induce endogenous synthesis of cholesterol. Statins are effective at lowering cholesterol levels by 20%–50% below the baseline. They are also known to have minimal side effects and do not affect growth [
The target LDL-C value is typically <130 mg/dL, but if the patient is at high risk, such as with familial hypercholesterolemia or diabetes mellitus, the target LDL-C level should be maintained below 100 mg/dL. If target levels are not achieved within three months, the statin dose can be gradually increased to the maximum amount.
Since statins are potentially teratogenic, it is essential for physicians to confirm that adolescent girls are not pregnant before initiating statin therapy.
Bile acid sequestrants are the first line of therapy for children with dyslipidemia as these compounds are not absorbed systemically [
Ezetimibe (a cholesterol-absorption inhibitor) enters the enterohepatic circulation and reduces bile acid reuptake as well as cholesterol absorption. Ezetimibe is approved in children older than 10 years of age at a dosage of 10 mg/day as an adjuvant to statin therapy. In adults, ezetimibe has been shown to reduce the LDL-C by 20% [
Therefore, niacin, fibrates, and ezetimibe should only be initiated after consulting with a lipid specialist. When these drugs are used in combination in children, they exert an increased combined effect, but the occurrence of side effects is not increased.
Atherosclerosis begins in childhood and can lead to CVD in adulthood. Early detection and proper management of dyslipidemia in children and adolescents are urgently needed to reduce adult CV morbidity. The 2017 Clinical Practice Guidelines for Dyslipidemia of Korean Children and Adolescents are intended to help identify children who are at increased risk of CVD and may benefit from the early screening and intervention of dyslipidemia. These guidelines provide a schematic approach that will help pediatricians make timely decisions regarding the screening and management of Korean children and adolescents with risks and conditions associated with accelerated atherosclerosis.
No potential conflict of interest relevant to this article was reported.
The authors greatly appreciate the members of Committee on Dyslipidemia of Korean Pediatric and Adolescents and the Korean Society for Pediatric Endocrinology for their support in developing and publishing these guidelines. This guideline is being simultaneously published in
Algorithm for dyslipidemia treatment. FLP, fasting lipid profile; LDL-C, low-density lipoprotein cholesterol; CHILD 1, Cardiovascular Health Integrated Lifestyle Diet 1; CHILD 2-LDL, Cardiovascular Health Integrated Lifestyle Diet 2; non-HDL-C, non–high-density lipoprotein cholesterol; TG, triglycerides; CVD, cardiovascular disease.
Definition of dyslipidemia in children and adolescents
Variable | Acceptable | Borderline |
Abnormal |
---|---|---|---|
Total cholesterol (mg/dL) | <170 | 170–199 | ≥200 |
LDL-C (mg/dL) | <110 | 110–129 | ≥130 |
Non–HDL-C (mg/dL) | <120 | 120–144 | ≥145 |
Triglyceride (mg/dL) | |||
0–9 years | <75 | 75–99 | ≥100 |
10–19 years | <90 | 90–129 | ≥130 |
HDL-C (mg/dL) | >45 | 40–45 | <40 |
LDL-C, low-density lipoprotein cholesterol; Non-HDL-C, non–high-density lipoprotein cholesterol; HDL-C, high-density lipoprotein.
Borderline values of total cholesterol and LDL-C represent the 75th–95th percentile.
Abnormal values of total cholesterol and LDL-C represent the 95th percentile, except for HDL-C which represents the 10th percentile. [
Adapted from National Heart, Lung, and Blood Institute 2011. [
Risk factors of dyslipidemia
Family history | |
Parent, grandparent, aunt, or uncle with a history of myocardial infarction, angina pectoris, coronary artery bypass/stent/angioplasty, sudden death under 55 years of age in male or under 65 years of age in female | |
High-level risk factors | |
Hypertension requiring medication | |
Smoking | |
BMI≥97th percentile | |
High risk conditions: type 1 diabetes mellitus, type 2 diabetes mellitus, chronic kidney disease/end stage renal failure/kidney transplantation, heart transplantation, Kawasaki disease with aneurysm | |
Moderate-level risk factors | |
Hypertension not requiring medication | |
95th percentile≤BMI<97th percentile | |
HDL cholesterol<40 mg/dL | |
Moderate risk conditions: Kawasaki disease with improved coronary artery aneurysm, chronic inflammatory disease (systemic lupus erythematosus, infantile rheumatoid arthritis), human immunodeficiency virus infection, nephrotic syndrome |
BMI, body mass index; HDL, high-density lipoprotein.
Screening for dyslipidemia
Age | Recommendation |
---|---|
Birth–2 yr | No lipid screening |
2–8 yr | No routine lipid screening |
Measure fasting lipid profile if child has a family history of dyslipidemia, moderate or high-risk factors and condition |
|
9–11 yr | Universal screening |
Measure nonfasting non–HDL-C | |
Fasting lipid testing if non-HDL-C≥145 mg/dL |
|
12–16 yr | No routine lipid screening |
Measure fasting lipid profile if child has a family history of dyslipidemia, moderate or high-risk factors and condition |
|
17–21 yr | Universal screening |
Measure nonfasting non-HDL-C | |
Fasting lipid testing if non-HDL-C≥145 mg/dL |
HDL-C, high-density lipoprotein cholesterol.
Two additional fasting lipid tests measured 2 weeks but within 3 months.
Recommendations of CHILD 1, CHILD 2-LDL, CHILD 2-TG diets
CHILD 1 |
CHILD 2–LDL (2–21 yr) | CHILD 2–TG (2–21 yr) | |||||
---|---|---|---|---|---|---|---|
Birth–6 mo | 6–12 mo | 12–24 mo | 2–10 yr | 11–21 yr | |||
Consult | Consult with a clinical nutritionist for clinical nutrition treatment for family members. | ||||||
Fat content | Exclusively breastfeeding should be done until 6 mo of age. | Continue breastfeeding until at least age 12 mo while gradually adding solids : transition to iron-for tified formula until 12 mo if reducing breastfeeding Infants under 12 mo of age should not limit their fat intake without medical indication. | Keep total fat at 30% of total calories and saturated fatty acid at 8%–10% of total calories. | Keep total fat at 25%–30% of total calories and saturated fatty acid at 8%–10% of total calories. | Keep total fat at 25%–30% of total calories and saturated fatty acid at 7% of total calories. | ||
If direct breastfeeding is impossible, use a breast pump, and if any breast feeding is not available, iron-fortified infant formula should be fed | Consume monounsaturated and polyunsaturated fatty acids up to 20% of the total calories. | Consume monounsaturated and polyunsaturated fatty | Consume monounsaturated fatty acids up to 10% of the total calories. | ||||
Cholesterol is limited to less than 300 mg per day. | Cholesterol is limited to less than 300 mg per day. | Cholesterol is limited to less than 200 mg per day. | |||||
Avoid trans fatty acids as much as possible. | Avoid trans fatty acids as much as possible. | Avoid trans fatty acids as much as possible. | |||||
Change to non-sugar, lowfat milk (containing no fat or 2% fat). | Consume nonsugar, low-fat milk. | ||||||
Sugar intake | 100% juice should be limited to about 120 mL per day, other beverages should not be fed, Encourage water | Limit sugar sweetened beverages intake and encourage water intake. | Limit sugar sweetened beverages and encourage water intake. | Reduce simple carbohydrate intake and increase complex carbohydrate intake. | |||
Consume beverages without simple sugars. | |||||||
Others | Encourage dietary fiber intake from food. | Increase fish intake to increase omega-3 fatty acid intake. | |||||
Recommend consuming fiber-rich natural foods (fruits, vegetables and grains), but do not recommend fiber supplements. Limit refined carbohydrate foods (sugar, white rice, white bread) | |||||||
Expert recommendations | Consult health-care provider about low-fat milk intake after 12 mo of age if a family history of obesity, heart disease, or dyslipidemia is present. | In children with familial hypercholesterolemia over 2 yr of age, vegetable sterols or stanols can be taken instead of other fats up to 2 g per day. | If obese, also limit caloric intake and increase activity levels. | ||||
Water-soluble fiber can be added to the low fat, low saturated fatty acid diets which can be added up to 6 g/day for children aged 2–12 yr and up to 12g/day for children aged 12 yr and older. | |||||||
All children are encouraged to engage at 1 hr of moderate physical activity per day, with television viewing, computer use, and cell phone use limited to less than 2 hr. |
CHILD 1, Cardiovascular Health Integrated Lifestyle Diet 1; CHILD 2-LDL, Cardiovascular Health Integrated Lifestyle Diet 2- low density lipoprotein cholesterol; CHILD 2-TG, Cardiovascular Health Integrated Lifestyle Diet 2-triglyceride.
Recommendations for pharmacological treatment of dyslipidemia
Age | Treatment | |
---|---|---|
Birth–9 yr | Pharmacological treatment is limited to children with homozygote familial hypercholesterolemia, LDL-C ≥400 mg/dL, primary hypertriglyceridemia (TG≥500 mg/dL), cardiovascular disease, and cardiac transplantation. | |
10–21 yr | Refer to lipid specialist | |
LDL-C ≥250 mg/dL or TG ≥500 mg/dL | ||
Statin treatment | ||
1) LDL-C ≥190 mg/dL | ||
2) LDL-C 160–189 mg/dL, and a positive family history of premature CVD in first-degree relatives or at least one high-level risk factor or risk condition or at least 2 moderate-level risk factors or risk conditions | ||
3) LDL-C ≥ 130–159 mg/dL, and at least 2 high-level risk factors or conditions or at least 1 high-level risk factor and 2 moderate-level risk factors or conditions | ||
Omega-3 fish oil | ||
TG ≥200–499 mg/dL, non-HDL-C ≥145 mg/dL | ||
Statin, fibrates, or niacin may be considered | ||
If non-HDL-C ≥145 mg/dL after LDL-C has reached the target level |
LDL-C, low-density lipoprotein cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol.
Major effects and dose of medications for dyslipidemia
Type of medication | Major effects | Adverse effects | Common names | Daily dose | FDA approval in children |
---|---|---|---|---|---|
HMG-CoA reductase inhibitors | ↓LDL cholesterol &TG, ↑HDL cholesterol | ↑Liver transaminases ↑Creatine kinase, myopathy, rhabdomyolysis | Lovastatin (Mevacor) | 20–80 mg | Approved |
Simvastatin (Zocor) | 20–80 mg | Approved | |||
Pravastatin (Pravachol) | 20–80 mg | Approved | |||
Atorvastatin (Lipitor) | 5–80 mg | Approved | |||
Cholesterol absorption inhibitors | ↓LDL cholesterol | Myopathy, gastrointestinal upset | Ezetimibe | 10 mg | Not approved |
Fibric acid derivatives | ↓TG, ↑HDL cholesterol | Dyspepsia, constipation, myositis, anemia | Gemfibrozil | 1,200 mg | Not approved |
Fenofibrate | 48–145 mg | Not approved | |||
Clofibrate | 2 g |
Not approved | |||
Omega-3-fish oil | ↓TG | Docosahexaenoic acid (DHA) | 2–4 g (adults) | Not approved | |
Nicotinic acid (extended release) | ↓TG & LDL cholesterol | Flushing, hepatic toxicity | 1,000–2,250 mg |
||
Bile acid sequestrants | ↓LDL cholesterol, ↑TG | Limited to gastrointestinal tract; gas, bloating, constipation, cramps | Cholestyramine | 8–16 g #2 | |
Colestipol | 2.5–20 g | ||||
Colesevelam | 1.25–4.375 g |
FDA, Food and Drug Administration; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; LDL, low-density lipoprotein; TG, triglyceride; HDL, high-density lipoprotein.
Lack of evidence-based research on dose in children.
Although used in clinical practice, there is a lack of evidence-based research in children.