Clinical Laboratory Strategies: September 30, 2010

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Considering Universal Cholesterol Screening for Children
Targeted Screening Misses Many Children with Dyslipidemia
By Bill Malone

Current National Cholesterol Education Program guidelines suggest selective cholesterol screening for children based on positive family history of premature cardiovascular disease, a parent with total cholesterol >240 mg/dL, or unknown family history. However, a recently published study found that this strategy missed about a third of children with moderate or severe dyslipidemia. This issue of Strategies explores its findings.

Familial hyperlipidemia (FH) and familial combined hyperlipidemia (FCH), disorders caused by mutations in the low density lipoprotein (LDL) receptor, can result in significantly elevated LDL cholesterol levels that frequently lead to premature cardiovascular disease (CVD). It’s also been clear for at least the past decade that fatty streaks and fibrous plaques start developing early in children with FH or FCH. Due to the genetic nature of these conditions, researchers have not been surprised to find that positive family history of coronary artery disease is strongly associated with hyperlipidemia in both children and adults.

Lacking definitive evidence that universal cholesterol screening of children would be appropriate, the National Cholesterol Education Program (NCEP) has recommended a selective approach to screening children, advocating screening children and adolescents whose parents or grandparents have documented coronary artery disease before the age of 55; who are the offspring of a parent who has been found to have a blood cholesterol level >240 mg/dL; and for whom family history is unobtainable, especially if they have risk factors such as hypertension or obesity.

Now a new study has added compelling evidence for universal screening, finding that relying on family history alone to decide which children should be screened for high cholesterol could miss many children who need treatment (Pediatrics 2010;126:260-265). The authors analyzed data of more than 20,000 5th  grade children in West Virginia, examining their family histories and fasting lipid profiles. More than 71% of the children met guidelines for cholesterol screening based on a family history of premature cardiovascular disease or dyslipidemia, defined as moderately elevated total cholesterol, low high-density lipoprotein, and high triglycerides.

Of those children whose family history did not indicate a need for screening, 9.5% had dyslipidemia, and 1.7% of these children warranted consideration for pharmacologic treatment according to NCEP and the American Academy of Pediatrics guidelines (LDL-C ≥160 mg/dL).  “It is very significant that the national guidelines for cholesterol screening among youth are not sensitive enough to pick up at least a third of children who have moderate to severe elevations in LDL cholesterol—high enough to fulfill other national guidelines for consideration of cholesterol-lowering medication,” said William Neal, MD, an author of the study. “That doesn’t necessarily mean that a physician would always start cholesterol-lowering medication at that level, but it’s high enough—well above 130 which is the upper limit of normal—and above 110, which is the upper limit of desirable normal, and sufficiently high to cause plaque formation in the arteries over time.” Neal is professor of pediatrics and the James H. Walker Chair of Pediatric Cardiology at the West Virginia University Center for Cardiovascular and Respiratory Sciences.

The genesis of the study came out of Neal’s award of a Centers for Disease Control and Prevention grant, “Addressing Familial Hypercholesterolemia: A Model Program for States.” Under this grant, Neal and his colleagues were supposed to devise a unique program that would identify children at very high genetic risk of dyslipidemia. Neal’s approach took the form of population-based screening among all 5th grade children in West Virginia whose parents chose to allow them to participate. The study started out in three counties and every year, doubled the number of counties. Since 2002, the Coronary Artery Risk Detection in Appalachian Communities project has offered cholesterol screening to every 5th grader in the state.

Neal believes the study, along with other evidence, could lead to screening more children in other states, and contended that universal screening, as opposed to currently recommended targeted screening, is not actually that big of a leap. “At least in our population, more than 50 percent of children already meet guidelines for screening, so it’s not a totally foreign concept,” Neal said. “I know that the American Academy of Pediatrics is very interested in this, and new screening guidelines will come out in 2011, so I’m sure they’ll consider our data. I don’t know what the ultimate decision will be, but it may well be to recommend universal screening.”

Despite the massive size of the study and the clear gap in current screening guidelines, not all clinicians will be eager to screen every child or be confident with what to do with results, said Sridevi Devaraj, PhD, a professor at UC Davis Health Systems’ Laboratory for Atherosclerosis and Metabolic Research. She is also director of toxicology and special chemistry, and co-director of the translational program at UC Davis in Sacramento, Calif. “This area is very controversial, in part because of the issue of expense in universal screening,” she said. “In a way, this study is a targeted strategy. In West Virginia, it is well know that this population has a very high risk for coronary artery disease, so in this particular area, it makes sense. In regions where you have higher cardiovascular disease, it may not be a bad idea to focus on children. Maybe not everywhere, but something targeted.” However, Devaraj pointed out that many clinicians have valid concerns about giving statins to children due to possible diabetes risk over time, as well as a lack of multicenter trials showing efficacy and safety. Devaraj was not associated with the study.

Neal underscored the fact that the study is not focused on high cholesterol resulting from lifestyle factors and obesity, but rather on the small percentage of children with FH or FCH who likely will develop CVD regardless of their weight or their diet. “We know that high LDL-C leads to early coronary disease, and we know that statins, even if given at a young age, will slow down or stop that progression,” he said. “There is also tremendous natural history data that left untreated, people who have FH are going to have coronary events in the 30s, 40s, or at latest 50s.” Considering the almost certain bad outcomes for children with FH or FCH, Neal emphasized that current guidelines should be sufficient to help physicians decide on treatment for children with dyslipidemia, leaving gaps in screening as the logical target for improvement.

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