Abstract
The past few decades have shown an increase in the prevalence of chronic conditions in the pediatric population. One of the chronic conditions that appears to be on the rise in this population is hypercholesterolemia. At the same time, the rate of obesity is increasing in children and adolescents and may be putting our youth at risk for abnormal lipid levels. First-line prevention and treatment should involve intensive lifestyle medicine therapy. If warranted, however, the use of medications may be started as early as 8 years of age, but this has many unknown variables related to safety and efficacy. Caution and vigilant observation for drug interactions and adverse events is warranted by the health care team and family members throughout treatment with drug therapy.
Pediatric health care has traditionally focused on acute care illnesses. However, over the past couple of decades, there has been an increase in the prevalence of chronic conditions in the pediatric population. An article written by Wise in 2007 about the “future pediatrician” reported data from the National Health Interview Survey that showed that only 2% of all children were diagnosed with a chronic condition in 1962. 1 By the year 2003, however, this had risen to approximately 8%. 1 During this time period, the incidence of overweight and obesity in the pediatric population tripled, leading many to believe this to be a primary cause for the rise in chronic conditions. Additionally, the National Hospital Discharge Survey reported that only 25% of all hospital admissions were a result of chronic conditions in 1962, which compares to more than 50% of admissions in 2003. 1 One chronic condition that appears to be on the rise in the pediatric population is hypercholesterolemia.
Screening for Preventable Chronic Conditions
Cardiovascular disease (CVD) remains the leading cause of death among adults in the United States, but a diagnosis of CVD in children and adolescents is rare. However, risk factors that accelerate the development of CVD begin in childhood, and there is increasing evidence that risk reduction delays progression toward clinical disease. 2 In late 2011, the National Heart, Lung and Blood Institute (NHLBI) published the “Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents,” which provides a great deal of information about screening and prevention of cardiovascular risk in the pediatric population. 1 Many of the recommendations provided by the NHLBI support screening for CVD risk factors very early in life with a focus on proper nutrition, physical activity, and avoiding exposure to tobacco smoke. Body mass index (BMI) and blood pressure should be measured in all patients starting at ages 2 and 3 years, respectively; a fasting lipid panel starting between the ages of 1 and 4 years in those with a family history of hypercholesterolemia or who have parents with high cholesterol is recommended, and screening for diabetes with a fasting glucose measurement should begin by age 9 years. 2
Hyperlipidemia
Observational studies have demonstrated a clear correlation between lipoprotein disorders and the onset and severity of atherosclerosis in children, adolescents, and young adults. 2 The predominant pattern of dyslipidemia in childhood consists of a combination of obesity, with moderate to severe elevation in triglycerides (TG); normal to mild elevation in low-density lipoprotein cholesterol (LDL-C); and/or a reduced high-density lipoprotein cholesterol (HDL-C) level. The combination of these dyslipidemic patterns have been shown to be associated with the initiation and progression of atherosclerotic lesions in children and adolescents, as demonstrated by pathology and imaging studies. 2
In 2010, the Centers for Disease Control and Prevention (CDC) published a report on an analysis of the National Health and Examination Survey (NHANES) for 1999 to 2006 on the prevalence of abnormal lipid levels among US youths. 3 For the purposes of the CDC’s report, abnormal lipid levels were defined as having any of the following: LDL-C ≥ 130 mg/dL; HDL-C ≤ 35 mg/dL; or TG ≥ 150 mg/dL. The report found that the prevalence of abnormal lipid levels among youth aged 12 to 19 years varied by BMI, but was 20.3% overall. 3 More specifically, normal weight youth showed a prevalence of 14.2%, whereas overweight and obese youth had a prevalence of 22.3% and 42.9%, respectively. 3 This analysis also showed that among all youth, 32% demonstrated a BMI ≥30 kg/m2. 3
In 2002, the American Academy of Pediatrics (AAP) established recommendations for targeted screening of children aged ≥2 years for abnormal lipid levels. 4 Under these recommendations, any child ≥2 years of age and demonstrating a high BMI would be a candidate for lipid screening. Therefore, according to the CDC’s analysis of the NHANES data, nearly one third of youth in the United States between 12 and 19 years of age would be candidates for lipid screening.
It is important to note the need to rule out familial hypercholesterolemia when screening and assessing lipid levels in the pediatric population. It is estimated that only about 20% of individuals with familial hypercholesterolemia are currently diagnosed and that most individuals with the disorder will have a cardiac event or stroke first before a diagnosis is made. 5 This article does not specifically focus on familial hypercholesterolemia. However, health care professionals who work with the pediatric population and screen for lipid levels should become familiar with screening for this disorder and refer patients to a lipid specialist as necessary.
It is also important to rule out secondary causes of hypercholesterolemia when screening for lipid disorders. Certain medications such as corticosteroids, isoretinoin, β-blockers, some oral contraceptives, select chemotherapeutic agents, and select antiretroviral agents can cause lipid abnormalities. Endocrine-related disorders such as hypothyroidism/hypopituitarism, diabetes mellitus types 1 and 2, and polycystic ovary syndrome can also increase lipid levels. In addition, other conditions related to renal, hepatic, and infectious diseases and inflammatory disorders have also been shown to increase lipid levels. 2
As with the adult population, lifestyle medicine strategies are recommended as first-line therapy for the treatment of hyperlipidemia in the pediatric population. Lifestyle medicine may be even more important for the pediatric population compared with adults because of the limited amount of information on the safety and efficacy of lipid-lowering drugs in this age group. As a result, youth who demonstrate abnormal lipid levels should undergo intensive lifestyle medicine therapy prior to initiation of drug therapy.
Drug Therapy
If lifestyle medicine therapy over a period of 6 to 12 months fails to achieve adequate lipid levels in the pediatric population, drug therapy is permitted and recommended. 6 A study published in 2008 reported that use of medications in the pediatric population for the treatment of abnormal lipid levels increased by 15% between 2002 and 2005. 7 The National Cholesterol Education Program recommends that drugs should only be administered to patients who are older than 10 years. 6 However, the American Heart Association and the AAP both support the use of lipid-lowering drug therapy in patients as young as 8 years of age.4,6,8
Similar to adults, statin therapy is considered first-line treatment for pediatric patients with abnormal lipid levels. 6 The Food and Drug Administration (FDA) has approved all the currently available statin medications (atorvastatin, simvastatin, rosuvastatin, lovastatin, and fluvastatin) for use in patients starting at 10 years of age, with the exception of pravastatin, which has approval to be given to children as young as 8 years. The use of statin medications was approved for patients at these young ages largely because of the need for effective treatment of familial hypercholesterolemia. However, the use of drug therapy in pediatric patients for the treatment of lipid disorders may be on the rise because of abnormal lipid levels resulting from unhealthy lifestyle behaviors rather than familial hypercholesterolemia. Long-term safety and efficacy data for the use of statins in the pediatric population currently does not exist. Most of the medications have been studied for only 2 years, which leads some to criticize its use in this age group.
Health care professionals treating pediatric patients with drug therapy for abnormal lipid levels should be vigilant in observing medication adherence and potential adverse reactions with the use of statins. The most common side effects in pediatrics are related to flu-like symptoms. However, monitoring liver function, creatine kinase, growth, and sexual maturation should be strongly considered. Additionally, all statin medications are contraindicated in pregnant women. Therefore, pediatric female patients should be counseled on the use of contraception while taking statin medications. Potential drug-drug interactions with statin medications that may be pertinent to this population include cyclosporine, niacin, fibric acid derivatives, erythromycin, azole antifungals, and nefazodone. Screening for potential drug-drug interactions must be a priority at each contact with the patient to prevent potentially serious complications with statin use.
Conclusions
The risk factors leading to CVD that can ultimately occur in adulthood are present in childhood for many individuals. Proper screening, mitigating the onset, and effective treatment of CVD risk factors, such as hypercholesterolemia, is an important component of pediatric health care. Using medications to treat abnormal lipid levels in children and adolescents has many unknown variables related to safety and efficacy. Intensive lifestyle medicine therapy should always be tried for 6 to 12 months prior to the initiation of drug therapy, except for individuals with familial hypercholesterolemia. If drug therapy must be implemented in pediatric patients, statin medications should be used as first-line therapy. Caution and vigilant observation for drug interactions and adverse events are warranted by the health care team and family members throughout treatment with drug therapy.AJLM