Pediatric Annals

Healthy Baby/Healthy Child 

Overview of Dyslipidemia in Childhood and Adolescence: Why Does It Matter and What Do We Do About It?

Leah Khan, MD

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality in adults in the United States. Cardiovascular health as a child and adolescent is important in setting the path for a heart-healthy life in adulthood. One major impact on cardiovascular health that can have its roots in childhood is dyslipidemia. Universal screening for all children is a newer concept that has emerged over the last decade; previously children and adolescents were screened based only on risk factors. This review addresses who is at risk for dyslipidemia, how and when to screen children and adolescents, why early identification is important, and how to manage dyslipidemia when it is diagnosed. There are many interventions that can be started in childhood to help decrease cardiovascular risk factors in adults, thus decreasing the morbidity and mortality from heart disease in the future. [Pediatr Ann. 2021;50(1):e4–e9.]

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality in adults in the United States. Cardiovascular health as a child and adolescent is important in setting the path for a heart-healthy life in adulthood. One major impact on cardiovascular health that can have its roots in childhood is dyslipidemia. Universal screening for all children is a newer concept that has emerged over the last decade; previously children and adolescents were screened based only on risk factors. This review addresses who is at risk for dyslipidemia, how and when to screen children and adolescents, why early identification is important, and how to manage dyslipidemia when it is diagnosed. There are many interventions that can be started in childhood to help decrease cardiovascular risk factors in adults, thus decreasing the morbidity and mortality from heart disease in the future. [Pediatr Ann. 2021;50(1):e4–e9.]

High cholesterol is not something that we usually associate with children, as most of the outcomes related to abnormal cholesterol are seen in adulthood. However, an increasing number of studies are showing that lipid abnormalities in childhood often lead to poor cardiovascular health as an adult. For this reason, screening for and managing abnormal lipids early is important to improve the morbidity and mortality of this population in the future.

Ideal cardiovascular health includes seven components.1 There are three physiologic components, including maintaining optimal levels of total cholesterol, blood pressure, and fasting glucose.1 There are four behavioral components that include not smoking, having a normal body mass index, getting adequate physical activity, and a consuming a healthy diet.1 These components are interconnected, and abnormalities in one area often lead to abnormalities in other areas.

One major risk factor for cardiovascular disease (CVD) is dyslipidemia. Dyslipidemia is the term used for any abnormality in the lipid profile, which consists of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides;2 non–HDL-C is also sometimes included.2 Non–HDL-C comprises all of the cholesterol that is present in lipoprotein particles that are considered atherogenic, which includes LDL-C, liproprotein(a), intermediate-density lipoprotein, and very low-density lipoproteins.1,3 Dyslipidemia occurs when there is an elevation in TC, LDL-C, non–HDL-C, or triglycerides, or when there is low HDL-C.4,5 High TC is defined as >200 mg/dL, high non–HDL-C is >145 mg/dL, and low HDL is <40 mg/dL6 (Table 1).

Lipid Panel Values

Table 1.

Lipid Panel Values

What Causes Dyslipidemia?

There are both primary and secondary causes of dyslipidemia, and both can be present in the same person. Primary causes are genetic and include familial hyperlipidemia, familial combined hyperlipidemia, familial defective apolipoprotein B, dysbetalipoproteinemia, PCSK9 protein abnormalities, familial hypertriglyceridemia, and monogenic autosomal co-dominant disorders caused by mutations in the LDL receptor.3,7–9 Secondary causes include lifestyle factors such as obesity, high dietary intake of saturated fats, inactivity, and tobacco use, as well as diseases such as diabetes, liver disease, kidney disease, or underactive thyroid.3,7–11 Several drug classes may also increase cholesterol, including glucocorticoids, isotretinoin, and antiretroviral drugs.3,10 These secondary causes of dyslipidemia have increased significantly in recent years as the prevalence of the use of these drugs, as well as the obesity rate, have increased.10

In children and adolescents, there is a strong association between body mass index and abnormal lipid levels.12 This is evident most markedly in HDL-C and triglycerides, with children who are obese having a 2- to 6-fold higher odds ratio of abnormal lipids than children with normal weight.10,12,13 Excessive intake of saturated fat and trans fat also contributes to obesity and risk for abnormal lipid levels.3 Children with inappropriate body fat percentage and weight-to-height ratio are more likely to have higher LDL-C and non–HDL-C than their counterparts with normal weight.8 Research has shown that children with unhealthy habits and cholesterol abnormalities become adults with unhealthy habits and cholesterol abnormalities that lead to higher cardiovascular risk.7,9,14

Children's lipid values also tend to correlate with those of their adult family members.3,5 Children whose parents have dyslipidemia often have higher TC and triglyceride levels as children.5,11 Those with a family history of premature CVD (defined as a heart attack, treated angina, intervention for coronary artery disease, stroke, or sudden cardiac disease in men before age 55 years or a woman before age 65 years) are at higher risk for dyslipidemia in childhood as well.3,5 If there is a strong family history of CVD, thought should be given to whether there is a genetic component that may be contributing, as this population may need earlier intervention than those with secondary causes of dyslipidemia.

Who Gets Dyslipidemia?

Abnormal lipids in children are fairly common, most likely caused by the increases in obesity, sedentary lifestyle, and poor diet in recent decades.11 About 20% of children between the ages of 6 and 19 years have adverse levels of one or more lipid values.3,6 In one study, 7% of children had elevated TC, 6.4% had elevated LDL-C, and 10.2% had elevated triglycerides.3,6 More than 12% had low HDL-C, which is seen in 33% of children who are obese and 6.8% of children who are of normal weight.3,6 Abnormal lipid values are overwhelmingly more prevalent in children who are obese and overweight than in children of normal weight.6

Why Do We Screen for Dyslipidemia?

Screening for dyslipidemia in childhood is important because abnormal serum lipid levels in childhood are associated with dyslipidemia in adulthood, which increases the risk for atherosclerosis and cardiovascular disease. Excess LDL-C particles cause a chronic inflammatory condition that leads to aggregation of oxidized LDL-C on the artery walls.11 This buildup is what eventually leads to heart attacks, strokes, and other effects of CVD. HDL-C can be protective because it prevents the oxidation of LDL-C and, thus, aggregation on the artery walls; therefore, low levels of HDL-C also increase the buildup of LDL-C on artery walls.5

CVD is the leading cause of morbidity and mortality in the United States.1,3,12 If we can intervene early, we may be able to lower the risk of disease in adulthood. It has been found that abnormal lipids in childhood contribute to early atherosclerosis, and there can even be fatty streaks and fibrous plaques found during childhood and young adulthood.3,10 Identifying children with abnormal lipids and intervening early, especially in those who might need pharmacologic intervention, can decrease risk of morbidity and mortality in adulthood.3,4,10,15

Who Should Be Screened?

There are two approaches to screening for dyslipidemia during childhood: (1) universal screening for all children and (2) screening for only those with risk factors. In more recent years, there has been a trend toward universal screening for all children. A report from the American Academy of Pediatrics (AAP) in 2008 found that between 30% and 60% of children with dyslipidemia could be missed by using only selective screening based on risk factors.3,7,16 In 2011, the AAP endorsed the recommendation of the National Heart, Lung, and Blood Institute (NHLBI) that universal screening of children at age 9 to 11 years and again at age 17 to 21 years was warranted for early identification of dyslipidemia.2,3,12,14,15,17 The timing of these laboratory tests is important as lipid levels are fairly stable from about age 2 years until a child reaches adolescence, but during puberty the levels of TC and LDL-C tend to decrease, and then begin rising again in the later teen years.3 Screening in the mid-teen years may miss potentially affected children.

Prior to the NHLBI recommendation, it was uncommon to perform lipid screening in 9- to 11-year-old children, and only a minority of 17- to 21-year-olds had testing done.12,18 Cholesterol screening in the past was highly associated with obesity and age and also showed some correlation to higher blood pressure measurements.12,18 Essentially, those with clear personal risk factors were more likely to be screened. The new guidelines not only endorsed universal screening for all children but also selective early screening in those with risk factors, beginning at age 2 years and repeating every 1 to 3 years depending on lipid levels.3,9,15,18 Risk factors for dyslipidemia include family history of premature CVD (parents or grandparents with heart attacks or blocked arteries before age 55 years in men and before age 65 years in females), having a parent or grandparent with TC >240 mg/dL, or having an unknown family history.7,9

As more research has been done, it has become clear that testing based solely on family history or even on body mass index of the child, is not sufficient to catch the many children who have abnormalities of their lipid profile.3,7,12 For this reason, even those without risk factors should be screened at least twice during childhood and adolescence.

Fasting or Nonfasting Lipid Panel?

Although a fasting lipid panel provides the most accurate look at a patient's lipid profile, the differences between fasting and nonfasting laboratory results are often not significant.2,3 It is easier to screen with a nonfasting lipid panel because patients can complete the test while they are in the office and compliance with returning for a fasting laboratory test is low. Nonfasting HDL-C seems to be a sensitive screening tool for dyslipidemia in children and adolescents.3 Triglycerides tend to have the largest variance between the two types of tests.2 In children who are overweight and obese, there were no statistically significant differences between the fasting and nonfasting test results.2 For nonfasting screens, the highest false-positive rate is in triglycerides and the highest false-negative rate is in LDL-C.2 If cholesterol levels are elevated with a nonfasting lipid panel, further evaluation should be completed with two separate fasting lipid panels at least 2 weeks apart.3,13 Once the diagnosis of dyslipidemia has been made, other laboratory tests may be helpful in determining the cause, including serum alanine aminotransferase, serum albumin, blood glucose, renal function, and thyroid levels.3

Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) is the most common genetic form of dyslipidemia. It is an autosomal dominant disease that can be heterozygous or homozygous.15 It is most commonly caused by a mutation in the LDL-C receptor gene, which makes the body unable to clear LDL-C appropriately.15 Heterozygous FH is common and is found in about 1 in 200 to 300 people.15 Homozygous FH is less common and found only in 1 in 300,000 to 400,000 people.15 FH presents with elevated LDL-C (often from birth) and family members who also have elevated LDL-C or some classic physical examination findings.15 On physical examination, people with FH (particularly homozygous) may have tendon xanthomata (most often on the Achilles tendon and dorsum of the hands), tuberous xanthomata (on the extensor surfaces of the elbows and knees), xanthelasmas (on the eyelids), plantar xanthomas (on the palms and soles), or corneal arcus (white or gray rings around the cornea).15 Genetic testing should be offered to children with xanthomata or a clinical diagnosis of FH.15 Benefits of confirmation by genetic testing include improved adherence to recommended therapy, guidance for testing of other family members, and counseling for future pregnancy.15 Once a family member is diagnosed with FH, it is appropriate to screen other family members with a lipid profile to see if they are affected so as to provide early intervention.15 Those screened should include siblings, parents, grandparents, aunts, and uncles.15 Those with homozygous FH should be managed by a lipid specialist and require more comprehensive diagnostic testing including electrocardiogram, echocardiogram, functional cardiac testing, and coronary artery imaging.15

How Do We Manage Dyslipidemia?

Promoting healthy lifestyle habits from a young age will help to lower cardiovascular risk and reduce morbidity and mortality in adulthood.14 Food and lifestyle preferences are ingrained early and carry into adulthood.1,14 When children are young, their parents have a strong influence over their eating and exercise habits and should be encouraged to set a good example of how to lead a healthy lifestyle.1,11,13 There are many choices that can significantly lower risk of abnormal lipids. Some of these include a diet that consists of fruits, vegetables, whole grains, fat-free or low-fat dairy products, and proteins such as meat, poultry, fish, beans, eggs, and nuts.14 Along with a healthy and balanced diet, exercise is equally important.5 Children age 5 to 17 years should get at least 1 hour of moderate to vigorous physical activity every day.14 Older teens and young adults should have a goal of at least 2.5 hours per week of vigorous activity.14 Studies have shown that adults who had regular physical activity as children were 83% less likely to present with dyslipidemia when they were older.5 It is also important to avoid smoking.14

The initial approach to treatment of dyslipidemia is focused on a heart-healthy lifestyle with dietary modifications, increased physical activity, weight loss for children who are obese, and avoidance of nicotine.4,13,18 To be successful, these modifications should be taken on by the entire family, not just the affected child.10 Dietary measures include reduced intake of saturated fat, cholesterol, and trans fat, increased intake of dietary fiber, and a diet with a lot of fresh fruits, vegetables, and whole grains and high in polyunsaturated and monounsaturated fats.4 In 2008, the AAP made several new dietary recommendations in response to increases in obesity and dyslipidemia in children.10 In children who are at-risk, the recommendation changed from consuming whole milk to consuming low-fat milk products at age 1 year, saturated fat should comprise <7% and trans fat should comprise <1% of total daily caloric intake, dietary cholesterol should remain <200 mg/day, and fiber intake should equal the child's age in grams plus an additional 5 grams.10

Plant sterols and stanols, which are found in fruits, vegetables, vegetable oils, nuts, seeds, orange juice, yogurt drinks, cereal bars, and dietary supplements, can also help to reduce LDL-C, although there are currently no long-term data demonstrating a reduction in early CVD.4,10 It should be noted that plant sterols and stanols decrease the absorption of fat-soluble vitamins and beta carotene, so children who take the dietary supplement should also take a multivitamin.4 Consultation with a dietitian to help manage a heart-healthy diet is often helpful.4 Physical activity is another important component to maintaining normal lipid levels and there is evidence that children who have daily vigorous activity have a lower risk of CVD and better overall lipid levels.4 In children who are obese, weight loss can also be helpful.4

When lifestyle changes alone do not result in improvement of lipid levels, pharmacologic treatment with statins should be considered. Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that prevent the synthesis of cholesterol.10 They also increase the synthesis of the LDL receptors by the liver, thus increasing clearance of LDL-C.10 There are several statins that are approved by the US Food and Drug Administration for use in children, including lovastatin, simvastatin, pravastatin, rosuvastatin, and artorvastatin.4,10 Side effects with statins are rare, and this class of medications tends to be well tolerated.4 It is important to counsel adolescent girls that statins are teratogenic, so concurrent contraception is recommended in adolescent girls of childbearing age.4 Children with FH often require statin therapy even when lifestyle modifications are accomplished.4,10 Statins can be considered when a child is age 10 years and has reached Tanner stage 2 development in boys or menarche in girls.10 For those who are at high risk, starting after age 8 years may be appropriate.10 Statins provide an average LDL-C reduction of 25 to 40 mg/dL.4 The longest duration of follow-up studies in children taking statins at this point is only 2 years, so more information in the future will help determine how helpful statin treatment in children is long-term.10,13

Baseline laboratory results should be obtained before starting a statin, including a fasting lipid profile, serum creatinine kinase, serum alanine aminotransferase, blood glucose, hemoglobin (Hgb) A1c, and a pregnancy test in girls.4 Repeat testing should be done 8 weeks after the start of therapy.4 Treatment should be started at the lowest dose available and should be taken at night because that is when most LDL-C synthesis occurs.4 If goals are reached at the 8-week mark then the dose should stay the same; if goals are not met then the dose should be increased and laboratory results rechecked every 4 weeks until lipid management is successful or maximum doses are reached4 (Figure 1). When a stable dose is established, lipid levels, glucose, and HgbA1c should be checked every 6 months.4 Occasionally, an additional medication may be needed in addition to a statin.4 Choices would include ezetimibe or a bile acid sequestrant, and these medications should be managed by a pediatric lipid specialist.4

Management of elevated cholesterol in children older than age 10 years.4,7 The cardiovascular risk level guides management of abnormal lipids. At-risk includes obesity <99th percentile, insulin resistance with comorbidities, family history of premature cardiovascular disease, parent with dyslipidemia, smoke exposure, “white coat” hypertension, chronic inflammatory disease, HIV, history of Kawasaki disease with regressed coronary aneurysms, cardiomyopathy, congenital heart disease, childhood cancer, and those with depression and bipolar disorders.4 Moderate risk includes those with severe obesity >99th percentile, confirmed hypertension, heterozygous familial hypercholesterolemia (FH), predialysis chronic kidney disease, aortic stenosis or coarctation, childhood cancer with chest irradiation, more than three at-risk conditions.4 High-risk includes those with homozygous FH, diabetes (type 1 or 2), end-stage kidney disease, Kawasaki disease with persistent coronary aneurysms, solid-organ transplant vasculopathy, childhood cancer with stem cell transplant, multiple comorbidities with any moderate-risk factor, and two or more moderate or at-risk factors.4 TC, total cholesterol.

Figure 1.

Management of elevated cholesterol in children older than age 10 years.4,7 The cardiovascular risk level guides management of abnormal lipids. At-risk includes obesity <99th percentile, insulin resistance with comorbidities, family history of premature cardiovascular disease, parent with dyslipidemia, smoke exposure, “white coat” hypertension, chronic inflammatory disease, HIV, history of Kawasaki disease with regressed coronary aneurysms, cardiomyopathy, congenital heart disease, childhood cancer, and those with depression and bipolar disorders.4 Moderate risk includes those with severe obesity >99th percentile, confirmed hypertension, heterozygous familial hypercholesterolemia (FH), predialysis chronic kidney disease, aortic stenosis or coarctation, childhood cancer with chest irradiation, more than three at-risk conditions.4 High-risk includes those with homozygous FH, diabetes (type 1 or 2), end-stage kidney disease, Kawasaki disease with persistent coronary aneurysms, solid-organ transplant vasculopathy, childhood cancer with stem cell transplant, multiple comorbidities with any moderate-risk factor, and two or more moderate or at-risk factors.4 TC, total cholesterol.

When the lipid abnormality is primarily in the triglycerides, treatment should still initially begin with promoting optimal dietary changes and physical activity along with weight loss.4 Triglyceride levels >500 mg/dL, however, can lead to pancreatitis, and pharmacologic treatment may be warranted in those cases.4 Omega-3-fatty acids (ie, fish oil) may help to lower extremely elevated triglyceride levels and reduce the risk of pancreatitis. Fibric acid derivatives such as gemfibrozil and fenofibrate are used to treat hypertriglyceridemia in children.4 When used in conjunction with statins, there is a risk for myopathy and rhabdomyolysis, so this should be monitored.4 Pharmacologic therapy for triglycerides >400 mg/dL or triglycerides >150 mg/dL and LDL >145 mg/dL should be managed in conjunction with a lipid specialist.4

Conclusion

Abnormal cholesterol is much more common in children than one might think. It is important to screen all children and adolescents because many children will have abnormal lipids without any associated risk factors. Abnormal lipids in childhood often persist into adulthood and increase risk for CVD. Early identification and treatment, whether through lifestyle changes or medication, can help mitigate this risk and improve morbidity and mortality later in life.

References

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  6. Nguyen D, Kit B, Carroll M. Abnormal cholesterol among children and adolescents in the United States, 2011–2014. NCHS Data Brief. 2015;(228):1–8. PMID:26727279
  7. Ritchie SK, Murphy EC, Ice C, et al. Universal versus targeted blood cholesterol screening among youth: the CARDIAC project. Pediatrics. 2010;126(2):260–265. doi:10.1542/peds.2009-2546 [CrossRef] PMID:20624798
  8. Oliosa PR, Zaniqueli DDA, Barbosa MCR, Mill JG. Relationship between body composition and dyslipidemia in children and adolescents [article in Portuguese, English]. Cien Saude Colet.2019;24(10):3743–3752. doi:10.1590/1413-812320182410.17662017 [CrossRef] PMID:31577005
  9. American Academy of Pediatrics. Cholesterol levels in children and adolescents. Accessed December 7, 2020. https://www.healthychildren.org/English/healthy-living/nutrition/Pages/Cholesterol-Levels-in-Children-and-Adolescents.aspx
  10. O'Gorman CS, O'Neill MB, Conwell LS. Considering statins for cholesterol-reduction in children if lifestyle and diet changes do not improve their health: a review of the risks and benefits. Vasc Health Risk Manag. 2010;7:1–14. doi:10.2147/VHRM.S7356 [CrossRef] PMID:21339908
  11. Filgueiras MS, Vieira SA, Ribeiro AQ, Novaes JF. Family history is associated with the presence of dyslipidemia in pre-school children [article in Portuguese, English]. Rev Paul Pediatr.2019;37(1):41–48. doi:10.1590/1984-0462/;2019;37;1;00005 [CrossRef] PMID:30066825
  12. Margolis KL, Greenspan LC, Trower NK, et al. Lipid screening in children and adolescents in community practice: 2007 to 2010. Circ Cardiovasc Qual Outcomes. 2014;7(5):718–726. doi:10.1161/CIRCOUTCOMES.114.000842 [CrossRef] PMID:25160839
  13. Radaelli G, Sausen G, Cesa CC, Portal VL, Pellanda LC. secondary dyslipidemia in obese children - is there evidence for pharmacological treatment?Arq Bras Cardiol.2018;111(3):356–361. doi:10.5935/abc.20180155 [CrossRef] PMID:30156604
  14. Korioth T. Cholesterol screening in childhood can prevent health issues later. AAP News. 2012;33(2):31. doi:10.1542/aapnews.2012332-31e [CrossRef]
  15. Ferranti S. Familial hypercholesterolemia in children. UpToDate. Accessed December 7, 2020. https://www.uptodate.com/contents/familial-hypercholesterolemia-in-children.
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  17. American Academy of Pediatrics. AAP endorsement: screen all children ages 9–11 for cholesterol. Accessed December 16, 2020. https://www.aappublications.org/content/early/2011/11/11/aapnews.20111111-1
  18. Rodday AM, Leslie L, O'Connor K, Parsons S. Pediatric cholesterol screening and treatment. Accessed December 7, 2020. https://www.aap.org/en-us/professional-resources/Research/research-findings/Pages/Pediatric-Cholesterol-Screening-and-Treatment.aspx

Lipid Panel Values


TC (mg/dL) LDL-C (mg/dL) HDL-C (mg/dL) TG (mg/dL)
Acceptable <170 <110 >45 <75
Borderline 170–199 110–129 40–45 75–99
Abnormal >200 >130 <40 >100
Authors
Leah Khan, MD

Leah Khan, MD, is a Pediatrician, Park Nicollet Clinics.

Address correspondence to Leah Khan, MD, 300 Lake Drive East, Chanhassen, MN 55317; email: leahdkhan@outlook.com.

Disclosure: The author has no relevant financial relationships to disclose.

10.3928/19382359-20201207-01

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