Experts provide recommendations for genetic testing of familial hypercholesterolemia
A panel of experts believes genetic testing of individuals at risk of familial hypercholesterolemia (FH) could “alter the natural history” of the condition, which is estimated to be undiagnosed in more than 27 million people worldwide, including more than 1 million in the United States.
People with FH are six to 20 times more likely to develop heart disease during their lifetime than counterparts without the genetic disorder, likely as a result of the high cumulative burden of circulating cholesterol from an early age. Considering a first-degree relative of someone with FH also has a 50 percent chance of having the condition, FH represents a logical target for genetic testing, a team of 30 international experts wrote in a consensus statement published in the Journal of the American College of Cardiology.
“Diagnosing and treating FH in childhood reduces the risk of early heart disease by about 80 percent, which is why it’s so important to find families with FH and especially children who have this invisible, life-threatening genetic disorder,” first author Amy C. Sturm, MS, with Geisinger’s Genomic Medicine Institute in Danville, Pennsylvania, said in a press release. “In addition, understanding the exact genetic mutation can better inform the initiation and treatment of FH with more intense lipid-lowering therapies and ultimately improve outcomes.”
The consensus statement recommends offering genetic testing for patients with very high LDL cholesterol—above 160 mg/dL for children and above 190 mg/dL for adults—plus a family history of high cholesterol or early heart attack. Even in the absence of such a family history, the authors recommended offering screening for children with LDL levels above 190 mg/dL and for adults with persistent levels above 250 mg/dL. Cascade testing of close family members should also be considered when genetic variants are uncovered.
At the very least, the experts believe screening should include the genes encoding the low-density lipoprotein receptor, apolipoprotein B and proprotein convertase subtilisin/kexin 9 (PCSK9). These three genes account for the majority of FH cases, they noted.
“With costs of next-generation DNA sequencing continuing to fall, genetic testing for FH has become more accessible,” the authors wrote. “Recent research suggests that by incorporating FH genetic testing as the standard of care for patients and their relatives with definite, probable, or possible FH, diagnosis of FH will improve, relatives of index cases will be identified, and initiation of recommended (lipid-lowering therapies) can commence at younger ages, leading to improved clinical outcomes.”
The experts noted cost-benefit analyses are required to evaluate upfront costs of genetic testing versus its ability to extend life expectancies and reduce the burden of coronary artery disease. Also, they said further research is needed to gauge how willing patients are to accept genetic testing.
“Familial hypercholesterolemia is perhaps the biggest untapped opportunity to prevent premature cardiovascular disease,” said Katherine A. Wilemon, founder and CEO of the FH Foundation and a coauthor of the consensus statement. “It is vital that healthcare providers and individuals understand the importance of differentiating this genetic condition from life-style induced high cholesterol.”
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Correction: The wording of the fourth paragraph has been updated from a previous version of this story. The consensus statement authors recommended offering genetic testing to patients meeting the listed criteria, not that clinicians "should" perform screening in these patients.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.