Study Finds Widespread Screening for Rare Cholesterol Disorder Not Cost-Effective 

Screening all young people for a genetic form of dangerously high cholesterol could prevent heart attacks and strokes later in life, but would not be cost-effective under the current healthcare system, according to a new modelling study published in JAMA. 

Familial hypercholesterolemia (FH) is a genetic disorder that causes LDL (sometimes called “bad”) cholesterol levels to be unusually high. The condition begins at birth and can cause heart attacks at an early age, said Norrina Bai Allen, PhD, the Quentin D. Young Professor of Health Policy, who was a co-author of the study. 

“We’ve been struggling for a long time with how best to identify people with FH so that they can be treated early and aggressively,” said Allen, who also directs the Center for Health Services & Outcomes Research within the Institute for Public Health and Medicine (IPHAM). “That’s what this article is addressing: how to find this needle in the haystack, because while relatively few individuals have FH, they suffer major consequences.” 

First, investigators used an established cardiovascular disease policy model and estimated that under the status quo — where only occasional, opportunistic cholesterol testing occurs — all Americans from this simulated group would experience more than 3.1 million heart attacks and strokes. About 16,000 of those events would occur among people with FH, many of whom never know they have it. 

Investigators then simulated outcomes for a nationwide cohort of 4.2 million 10-year-olds, testing what would happen if every child received routine cholesterol checks and, if their levels were especially high, underwent genetic testing for FH. 

When investigators added universal FH screening in either childhood (age 10) or early adulthood (age 18), the change prevented 1,150 to 1,820 cardiovascular events, depending on the LDL cholesterol threshold used to trigger genetic testing. That reduction amounts to less than 0.1 percent of all projected heart attacks and strokes, though it represents major benefit for the individuals directly affected. 

On the other hand, the financial picture was not as encouraging. The cost of adding genetic testing on a population scale outweighed the health gains, according to the study. The most economically favorable option — screening 18-year-olds and only testing those with LDL cholesterol of at least 190 mg/dL — still cost about $290,000 per quality-adjusted life-year, nearly triple the conventional benchmark for cost-effective healthcare interventions. 

The study did offer a path toward improving cost-effectiveness: If people identified by the initial cholesterol test received significantly more consistent long-term monitoring and support for lifestyle changes, the screening strategy could become cost-effective. That optimistic scenario assumes widespread, sustained adherence to lipid testing and preventive care — something that has historically been difficult to achieve at a population level. 

“The findings speak to identify ways to do screening more efficiently, and also to the fact that we need better data to understand who’s likely to benefit and how we can change the system to support cost-effective screening,” Allen said. “We know that risk is accumulating for cardiovascular disease even at elevated lipid levels below these diagnostic thresholds. Expanding how we identify at-risk patients using age-specific thresholds or risk prediction scores may improve CVD screening.” 

For now, the findings highlight the challenge of balancing precision medicine with public health and healthcare budgets, Allen said. FH remains severely underdiagnosed in the U.S., and early treatment is known to dramatically reduce the risk of early heart disease. But the study suggests that large-scale genetic testing efforts may need to be paired with broader improvements in long-term cholesterol management to make financial sense. 

“The study really focuses on a relatively rare genetic disorder, but it really emphasizes the need for strong science to understand screening more generally,” Allen said. “There are things that we think are important but may not be cost-effective, and we really need to provide clinicians and patients and families with the best approaches to identifying people at high risk for future heart disease, not just from FH, but more broadly from hypertension and cardiometabolic disorders.” 

The study was supported by grants from the National Institutes of Health National Heart, Lung, and Blood Institute Agency for Healthcare Research and Quality, as well as the American Heart Association.