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Genetic Testing Identifies More Familial Hypercholesterolemia Cases and Reduces Healthcare Costs

Article by: David Kann, MD, MPH, FACC, FNLA & Cassie Hajek, MD, FACP, FACMG

Familial hypercholesterolemia (FH) is a genetic condition, passed down through family members. According to the Centers for Disease Control and Prevention, FH affects around 1 in 250 people in the United States1, however, only 10 percent of people know they have the condition. FH dramatically increases the risk of heart disease and myocardial infarction (MI) or heart attack. If left untreated, heart attacks occur in 30 percent of women by age 60 and 50 percent of men by age 501.

Fortunately, genetic testing can guide identification of FH to help providers and health systems improve outcomes, reduce mortality and reduce overall healthcare costs.

FH Often Goes Unnoticed

Often, the first sign of FH is having elevated low-density lipoprotein (LDL) or “bad cholesterol” levels. Healthy LDL levels are under 100 mg/dL — children and adults with FH typically have levels greater than 160 and 190 mg/dL, respectively. Total cholesterol, LDL, and high-density lipoprotein (HDL) — or “good cholesterol” levels — are usually only measured during routine screenings. Not everyone with FH will have physical signs, making the condition difficult to diagnose2. For example, corneal arcus, or a white/gray ring around the corneas in the eyes, is seen in roughly 30 percent of FH patients. Xanthomas, or fatty deposits underneath the skin, are even less common, seen in fewer than 15 percent of FH patients3.

However, FH can be challenging to detect based on LDL cholesterol levels alone. Research shows that not everyone who carries a gene mutation for FH will have LDL cholesterol levels meeting the diagnostic threshold for FH, however they have exposure to significantly elevated LDL across their lifetime which places them at elevated risk for cardiovascular events. This means that a significant set of FH-positive patients are missed during screening tests, which affects treatment decisions.

Uncovering heart risk with genetic testing

There is currently an unmet need for effective screening for patients with FH who may be carriers but not have high LDL cholesterol. The American Heart Association, the Dutch Lipid Clinic Network Diagnostic Criteria (DLCNC), and the Simon Broome Register Diagnostic Criteria all list genetic testing as key in definitive FH diagnoses. The CDC Office of Public Health Genomics has also classified FH as Tier 1 on a recommended list for genetic screening, particularly for cascade testing in relatives of those with confirmed FH3.

Healthcare systems may opt to offer genetic screenings in partnership with large-scale population genomics programs like Helix to identify FH patients as early as possible. Variants in genes involved in LDL cholesterol metabolism and recycling have previously been studied, including the LDL-receptor (LDLR) gene, PCSK9, and APOB3.

By detecting FH early, healthcare providers can start cholesterol-reducing therapy early, improving patient health outcomes and overall survival. A recent 2022 study from researchers in Canada found that performing genetic testing costs less and is more effective in diagnosing FH compared to not performing genetic testing. It also reduced the number of cardiovascular events and improved quality-adjusted life-years (QALYs) for participants. Relatives of those with an FH diagnosis were also effectively tested with a combination of lipid and cascade screenings.

Together, it’s estimated that these screening strategies would save Ontario upwards of $141 million over the next five years5"

The key to reducing healthcare system costs lies in providing more preventive care rather than acute care and treatment. Cardiovascular disease (CVD) continues to be a heavy burden on these systems, with direct costs estimated to be nearly $444 billion. CVD care costs account for $1 out of every $6 spent on healthcare6. Studies in patients with borderline risk of atherosclerotic cardiovascular disease (ASCVD) have shown that extending statin therapy is cost-effective7.

Genetic testing is also invaluable in guiding therapy choice. For example, patients with FH caused by a PCSK9 gene mutation are particularly responsive to PCSK9 inhibitors. On the other hand, those with homozygous FH  with two non-functioning LDLR genes see little to no benefit from PCSK9 inhibitors. Knowing a patient’s genotype can guide treatment decisions, ensuring they receive the most effective therapy3.

Health systems have the opportunity to deploy genetic screening within their patient populations to detect FH and identify additional cases through family members. By finding previously undetected patients and guiding them to proactive, preventative care, total costs may be significantly reduced while improving patient survival.

Author bios:

David Kann, MD, MPH, FACC, FNLA is the Medical Director of Precision Medicine at WellSpan Health. He earned an AB in Science Technology and Society from Vassar College, an MPH from Columbia University where he studied health administration and epidemiology and an MD from Hahneman University. He completed his residency in internal medicine at Presbyterian Hospital of the University of Pittsburgh and his fellowship in cardiology at the University of Pennsylvania. He is a Fellow of the American College of Cardiology and of the National Lipid Association.

Cassie Hajek, MD, FACP, FACMG, is Medical Director at Helix. She graduated from the University of South Dakota Sanford School of Medicine and completed her Internal Medicine residency at Montefiore Medical Center in Bronx NY. Before completing her medical genetics fellowship at the UCLA Intercampus Medical Genetics Program, she practiced outpatient internal medicine at Sanford Adult Medicine in Sioux Falls.


  1. Centers for Disease Control and Prevention. Familial Hypercholesterolemia.
  2. Masana L, Zamora A, Plana N, et al. Incidence of cardiovascular disease in patients with familial hypercholesterolemia phenotype: Analysis of 5 years follow-up of real-world data from more than 1.5 million patients. J Clin Med. 2019;8(7):1080.
  3. Sturm AC, Knowles JW, Gidding SS, et al. Clinical genetic testing for familial hypercholesterolemia: JACC scientific expert panel. J Am Coll Cardiol. 2018;72(6):662-680.
  4. Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157(1):111-117.e.2
  5. Ontario Health (Quality). Genetic testing for familial hypercholesterolemia: Health technology assessment. Ont Health Technol Assess Ser. 2022;22(3):1-155.
  6. Shaw LJ, Goyal A, Mehta C, et al. 10-year resource utilization and costs for cardiovascular care. J Am Coll Cardiol. 2018;71(10):1078-1089.
  7. Kohli-Lynch CN, Bellows BK, Thanassoulis G, et al. Cost-effectiveness of low-density lipoprotein cholesterol-level guided statin treatment in patients with borderline cardiovascular risk. JAMA Cardiol. 2019;4(10):969-977.


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