To Screen or Not to Screen: That Is the Cholesterol Question

Just after publication in 1992 of reports by the National Cholesterol Education Program and the American Academy of Pediatrics on cholesterol screening in children, I asked the late Dr Ronald M. Lauer, who chaired both reports, why he advocated for opportunistic, rather than for universal, cholesterol screening in children.1 He answered with a question, “Do you really need to know a child’s cholesterol level to provide advice on heart disease prevention?” Dr Lauer was a visionary and founded the Muscatine Study, with goals of understanding the distribution of cardiovascular risk factors in children, their tracking into adulthood, and their associations with markers of subclinical cardiovascular injury and cardiovascular outcomes in adulthood.In this issue of Pediatrics, Nuotio and colleagues use data provided by the Muscatine Study and 6 other studies (the i3Ccollaborative) to provide an answer to this question: No.2 The authors were able to show that the incremental value in knowing lipid values did not substantially improve risk prediction for adult heart disease. These data provide strong support for both office-based efforts to control easily identified and modifiable risk factors (eg, hypertension, obesity, tobacco use, physical inactivity) and public health approaches directed at the same goals.However, having knowledge about general dyslipidemia is not the only reason to perform a lipid profile in childhood. Familial hypercholesterolemia (FH) is an inherited cause of elevated low-density lipoprotein cholesterol, affecting about 1:300 people worldwide, and causing premature heart disease, if untreated.3 There are likely 30 to 40 people with FH in the i3C cohort, too small a number to provide outcome data, particularly if some of these individuals received statin treatment as a result of knowing their lipid levels.The American Academy of Pediatrics’ position on cholesterol screening was updated in 2011 to include universal screening for cholesterol aged 9 to 11 years, as well as opportunistic screening, beginning at age 2 years, of those with a positive family history suggestive of FH, and also those with an additional major cardiovascular risk factor such as diabetes, hypertension, tobacco use, or severe obesity.4 Adding the recommendation for universal screening relied on 3 findings: Family history was insufficient to accurately discriminate those who were more likely to have FH from those who did not, tracking of lipid levels from childhood to adulthood provided a rationale to identify those who would be dyslipidemic adults earlier in life, and the obesity epidemic, which created a large population of children who might benefit from knowing their lipid levels. Because >30% of US children would be eligible for opportunistic screening based on obesity and there would be many children with FH among those not screened based on family history, universal screening for lipids seemed logical.Since 2011, and as demonstrated in the report by Nuotio et al, the case for measuring lipids to identify mild-to-moderate dyslipidemias, those that would typically be treated by diet and weight management, has grown considerably weaker.2 Evidence to support the American Academy of Pediatrics guidelines for obesity management demonstrates that weight control will improve dyslipidemia.5 Both the bariatric surgery experience and clinical trials in adults of weight management medications to control obesity and diabetes highlight the primary importance of controlling obesity for prevention of future cardiovascular disease.6By contrast, the case for cholesterol testing to identify FH has strengthened.3,7 Worldwide, and in contrast to the United States, cascade genetic testing of index adult cases of FH has identified a large number of affected children. Several countries now have, or are piloting, universal lipid screening programs, either in early childhood or in newborns. Outcome studies provide strong observational evidence of the benefit of treatment of FH beginning in adolescence, essentially eliminating heart disease before 40 years of age or about 25% of first heart attacks.8 Current experience suggests that anytime in childhood is the best age for FH identification; finding 1 child with FH typically leads to finding 1 or 2 undiagnosed relatives, also in need of lipid-lowering therapy.9In 2024, the question is now, “Which children’s cholesterol levels do we need to know to provide advice on heart disease prevention?” A small group of children have firm indications for cholesterol testing, based on high risk for heart disease before the age of 50 years (Table 1). These include children with a family history consistent with FH, with conditions associated with premature heart disease (eg, childhood cancer, chronic kidney disease), and with established cardiovascular risk factors, because the presence of dyslipidemia added to those risk factors doubles cardiovascular risk.10,11 All children should receive FH screening, either at 9 to 11 years as currently recommended, or at any age >2 years, with either a fasting or nonfasting lipid profile. A level of ≥160 mg/dl for low-density lipoprotein cholesterol or 190 mg/dl for nonhigh-density lipoprotein cholesterol remain the thresholds for FH evaluation.