In the United States, one in every 250 people has inherited a genetic variant that leads to dangerously high cholesterol levels from birth.
If high cholesterol isn't lowered early, people with this genetic condition, called familial hypercholesterolemia (FH), have a high risk of having a heart attack or stroke as early as their 30s or 40s. But only about 1 in 10 of people living with FH (1.5 million Americans) is aware of their condition.
Andrew Moran
A new modeling study conducted by researchers at Columbia and Harvard Universities finds that while screening children or young adults for high cholesterol and FH genes would prevent a substantial number of premature heart attacks and strokes, such testing is currently too expensive to implement.
Instead, their study suggests that if a universal screening program led to more intensive monitoring and lifestyle changes in all children and young adults with high cholesterol-including those without FH genes-cholesterol screening would become cost-effective.
"Early recognition and management of high cholesterol, even in childhood, can prevent or delay heart attacks, strokes, and maybe even dementia later in life," says Andrew Moran, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and one of the study's senior authors.
"Screening for FH is important for kids and young adults-and their family members-so we need to find a cost-effective way to screen early for FH. For young people with severely high cholesterol but without known genetic cause, early cholesterol testing and management can also be the path to prevention."
One in five adolescents has some abnormality on their regular lipid screen. The American Academy of Pediatrics and the American Heart Association recommended that all children have their cholesterol measured between the ages of 9 and 11 to identify cholesterol disorders, but less than 20% of children receive such testing.
Study details
The researchers' model tested multiple scenarios of a two-stage screening strategy that first measured children's cholesterol levels (LDL-C) and then conducted genetic testing to identify FH genes in those with high cholesterol numbers. This study looked at screening children at age 10 or age 18 and how the screening and subsequent treatments could prevent heart disease decades later.
"Though FH is among the most common and severe genetic disorders, it's still relatively rare," says Moran. "Because of the high upfront costs of screening millions to find a relatively small number of people with FH genes, our modeling found that none of the combined cholesterol plus genetic screening strategies were cost-effective compared to usual care."
The model found that if cholesterol screening led to more intensive cholesterol management among all those with high cholesterol (LDL ≥130 mg/dL) regardless of genetic test result, screening in young adulthood (around age 18) would be the most cost-effective strategy.
Could newborn genetic screening be more effective?
Going forward, FH screening may be cost-effective if it is bundled with other, established childhood screening packages such as newborn screening.
A recent study that trialed paired cholesterol and genetic screening for FH from the blood spots collected for newborn screening shows that newborn FH screening may be feasible at scale. The Columbia and Harvard teams are working with those investigators to explore best approaches to newborn or infant FH screening.
An added benefit of childhood genetic testing for FH would be the opportunity to cascade screening and treatment to other family members who may also have unrecognized FH, a factor that the current model doesn't consider.
"We haven't landed on the best way to screen early for FH yet, but with our modeling, we're leveraging the best evidence and efficient computer modeling methods to arrive at the most promising approaches to test in real clinical trials of screening," Moran says.
References
More information
The study, "Familial Hypercholesterolemia Screening in Childhood and Early Adulthood: a Cost-Effectiveness Study," was published Nov. 9 in JAMA.
This work was supported by grants from the National Institutes of Health (R01HL141823, R01HL168379, and R01HL121230).
All authors: Brandon K. Bellows (Columbia), Yiyi Zhang (Columbia), Natalia Ruiz-Negrón, Dhruv S. Kazi (Harvard), Amit V. Khera (Harvard), Jessica G. Woo (University of Cincinnati), Elain M. Urbina (University of Cincinnati), David R. Jacobs Jr. (University of Minnesota), Norrina B. Allen (Northwestern University), John B. Wong (Tufts Medical Center), Sarah D. de Ferranti (Harvard), and Andrew E. Moran (Columbia).
Andrew Moran and Sarah de Ferranti have no conflicts of interest to report.
