Familial Hypercholesterolemia Benefits From Genetic Screening

In a statement published in the Journal of the American College of Cardiology, an international expert panel convened by The Familial Hypercholesterolemia Foundation discussed the rationale of genetic screening for familial hypercholesterolemia (FH), including the creation of a definitive diagnosis, the pathogenic variants associated with higher cardiovascular risk, the appropriate times to initiate therapy, how to improve treatment adherence, and the cascade assessment of at-risk family members.

According to investigators, genetic FH testing improves the likelihood of achieving a definitive diagnosis compared with previous diagnostic methods. Past diagnostics relied on a series of clinical variables at presentation, including increased low-density lipoprotein cholesterol (LDL-C) levels, premature heart disease history, familial history of hypercholesterolemia and/or heart disease, and DNA testing of a pathogenic variant associated with FH.

Additionally, genetic testing for FH may aid in greater risk stratification for heart disease. According to the investigators, individuals with no FH pathogenic variant and LDL-C levels ≥190 mg/dL have a 6-fold higher risk for coronary artery disease vs a 22-fold increased risk in patients with an FH pathogenic variant and LDL-C levels ≥190 mg/dL.

The utility of genetic testing for FH also extends to other family members, considering FH is an autosomal-dominant disorder. Screening at-risk family members of patients with FH, also referred to as “cascade testing,” may be helpful in identifying other people who might require treatment for the disorder. Genetic testing can also help clinicians guide therapy for patients with FH. For instance, FH caused by PCSK9 mutations is particularly responsive to PCSK9 inhibitors. Furthermore, FH genetic testing is highly discriminatory and is helpful to differentiate patients with compound heterozygous FH, heterozygous FH, homozygous FH, double heterozygous FH, and autosomal-recessive FH.

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“Most importantly, genetic testing provides a window of opportunity whereby we can identify those individuals at significantly higher risk than the general population for [coronary artery disease] at a given LDL-C level,” the panel wrote. “Family screening based on genetic results can be implemented to identify and treat those individuals with unrecognized FH.”


Sturm AC, Knowles JW, Gidding SS, et al; convened by the Familial Hypercholesterolemia Foundation. Clinical genetic testing for familial hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018;72(6):662-680.