Dyslipidemia Dyslipidemias are disorders characterized by abnormal lipoprotein metabolism resulting in increased total cholesterol (TC), increased low-density lipoprotein cholesterol (LDL-C), increased triglyceride, and/or decreased high-density lipoprotein cholesterol (HDL-C) These lipid abnormalities can be caused by genetic mutations, environmental factors such as diet and activity level, or secondary to other processes such as kidney disease and organ transplantation.99,100 The most important genetic dyslipidemia to consider is familial hypercholesterolemia (FH), which is caused by heterozygous or homozygous mutations in the gene encoding the LDL receptor or related proteins FH is likely when the fasting LDL-C level is 160 mg/dL or greater in childhood or 190 mg/dL or greater in adulthood, there is a positive family history of hyperlipidemia or premature coronary disease, and secondary causes (such as hypothyroidism) have been excluded.101 Heterozygous FH has an estimated prevalence of 1 in 250102 in the United States and accelerates atherosclerotic cardiovascular disease risk by up to 30 years,103 while homozygous FH has an estimated prevalence of 1 in 1 million to 1 in 160,000 and causes cardiovascular disease events in childhood.104 FH has the highest prevalence of all the genetic defects that cause significant premature mortality, and this formed the basis of early screening programs for childhood dyslipidemia, as described below When considering dyslipidemia in childhood, it is important to understand developmental changes in lipid levels that occur in healthy children.105,106 Lipids and lipoprotein levels start low at birth, rise slowly over the first 2 years of life, and then stabilize until puberty During puberty, cholesterol levels decrease before rising again in late adolescence and early adulthood In particular, the expected decline in cholesterol levels during puberty must be anticipated when interpreting and managing lipids in this age group Selective Screening Versus Universal Screening for Dyslipidemia There has been significant debate on the role of universal versus selective screening for dyslipidemias in children and adolescents In 1992, the National Cholesterol Education Program (NCEP) Expert Panel on Blood Cholesterol Levels in Children and Adolescents recommended targeting screening to children with family history of early coronary artery disease, family history of hypercholesterolemia, or unknown family history.107 Such a strategy seeks to identify children with FH However, after publication of the 1992 NCEP guidelines, new data were reviewed in the follow-up American Academy of Pediatrics report on Lipid Screening and Cardiovascular Health showing that selective screening missed between 30% and 60% of children with dyslipidemias.108 Children with FH may not be detected with this strategy if their parents are unaware of the family history, and in fact, screening children has been advocated as a strategy to identify adult relatives with this condition since the diagnosis may be more straightforward in childhood Moreover, with the continued increase in the prevalence of pediatric obesity, there has been a shift in the patterns of childhood dyslipidemia from primarily isolated elevated LDL-C due to FH to the increasingly common obesity-associated pattern: moderately to severely elevated triglycerides, decreased HDL-C, and normal to mildly elevated LDL-C Both patterns are associated with accelerated atherosclerosis Because childhood dyslipidemia is identifiable, tracks into adulthood, and is amenable to intervention, the 2011 NHLBI Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents recommend universal screening before puberty (9 to 11 years of age) and again after puberty (18 to 21 years of age).98 Recommended Screening for Dyslipidemia As mentioned above, the NHLBI Guidelines provide age-specific recommendations for pediatric providers to screen for cardiovascular disease risk factors including dyslipidemias The document also provides guidance on reinforcing healthy lifestyle habits and providing treatments to decrease these risk factors, starting in infancy For dyslipidemia, the Guidelines recommend: ■ Universal screening at 9 to 11 years of age (before puberty) and again at 18 to 21 years of age (after puberty) with random non–HDL-C level or fasting lipid profile ■ Screening from 2 to 8 years of age and 12 to 16 years of age with a fasting lipid profile only if there is a positive family history, other risk factors for cardiovascular disease, or a moderate- or high-risk condition ■ No routine lipid screening from birth to 1 year of age The above guidelines are delineated in great detail in the 2011 NHLBI Cardiovascular Risk Guidelines, as mentioned.98 The reader is referred to this review for additional details Future Considerations for Dyslipidemia Screening In 2016, the United States Preventive Services Task Force reviewed the literature and concluded that there is insufficient evidence to assess the benefit of universal versus targeted screening for dyslipidemias in children and adolescents.109 This conclusion was based on a lack of large, randomized control trials in the pediatric population evaluating targeted versus universal screening for dyslipidemia and effectiveness of early detection and treatment on intermediate and long-term outcomes As mentioned above, the long timeline (decades), cost, and ethical considerations of such studies in children are prohibitive Modeling approaches may offer some insight into these questions, but to date these data are lacking However, available data indicate that initiation of statin therapy in children and adolescents with high LDL-C due to familial hypercholesterolemia restores endothelial function and slows or even reverses progression of atherosclerosis as indicated by carotid intimal media thickness.110–113 Importantly, multiple studies have demonstrated the safety of statin therapy in children and adolescents.114 Furthermore, clinical trial data indicate that lifestyle modification can improve intermediate outcomes in children with multifactorial dyslipidemia.115 Given the relatively high prevalence of FH as the prototypical genetic dyslipidemia and the very high prevalence of obesity in children, effective dyslipidemia screening in the younger populations will continue to have an important role in decreasing ... However, after publication of the 1992 NCEP guidelines, new data were reviewed in the follow-up American Academy of Pediatrics report on Lipid Screening and Cardiovascular Health showing that selective screening missed between 30% and 60% of children with... since the diagnosis may be more straightforward in childhood Moreover, with the continued increase in the prevalence of pediatric obesity, there has been a shift in the patterns of childhood dyslipidemia from primarily isolated elevated... Recommended Screening for Dyslipidemia As mentioned above, the NHLBI Guidelines provide age-specific recommendations for pediatric providers to screen for cardiovascular disease risk factors including dyslipidemias The document also provides guidance on