Genetic testing can help with diagnosis of familial hypercholesterolemia, a largely unknown disease
One of the great many benefits of medical and scientific advances is the ability to determine the presence of ‘silent-killer’-type disease and conditions before they can strike. It begins with simple measures—screenings for breast and colon cancer, for example, can begin at an earlier age or conducted more frequently for those with family histories.
But the next level is for conditions such as familial hypercholesterolemia (FH), a common but vastly underdiagnosed condition that affects approximately 1.3 million Americans. What’s more, about 90 percent of these people have no idea they carry the condition.
What is FH?
FH is an inherited disorder that can lead to heart attacks, stroke, and premature cardiovascular disease. As previously stated, it’s fairly common yet largely unknown.
In FH, genetic mutations render the body incapable of removing LDL, or ‘bad’ cholesterol. This lead to high levels of cholesterol and early-onset cardiovascular disease.
Worse still, the typical recommendations of ‘watch your diet, and get more exercise’ will do little, if anything, to help an individual with FH. Most of the cholesterol in the body is not consumed via food; rather, it’s produced by cells, and the liver is responsible for its removal. As you might imagine, each person’s liver does so at different speeds and rates of efficiency. In people with FH, this is where the trouble starts. The genetic mutations cause their liver to process the LDL cholesterol very slowly or sometimes not at all, resulting in dangerously high cholesterol levels.
Two different forms of FH can affect carriers in different ways. Heterozygous FH (HeFH) indicates you have inherited this genetic mutation from one parent. HeFH occurs in 1 in 250 people worldwide.
But Homozygous FH (HoFH) indicates an inheritance of FH from both parents—a condition much more severe in its consequences. Luckily, HoFH is exceedingly rare, occurring in about 1 in 160,000 to one million people worldwide.
Adults with FH may have untreated LDL-C levels that range from 190mg/dL to 400mg/dL or even higher. Children with FH generally have LDL-C levels above 160mg/dL, but in pre-teens, levels can be even lower.
If left untreated, FH leads to a 50 percent increase of probability of a heart attack in men before age 50, and a 30 percent increased chance of a heart attack in women before age 60.
The Importance of Genetic Testing
With all these statistics in mind—particularly the one that indicates about 90 percent of FH carriers are unaware of the condition—it makes ample sense to encourage early testing. Luckily, earlier this summer an international panel of about 30 cardiovascular, lipid, genetics, and advocacy experts convened to author a consensus statement on diagnosis—a statement that was published in the Journal of the American College of Cardiology. The statement recommended offering genetic testing to diagnose individuals with FH and their relatives.
“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,” said Amy C. Sturm, MS, CGC, Genomic Medicine Institute, Geisinger, and co-author of the paper. “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.”
Patients with very high LDL cholesterol or a positive family history of high cholesterol or early heat attack are at the top of the recommended list for testing. These people are considered to have “definite or probable” FH, and require testing for the presence of any of the three genetic variants attributed to most FH cases and blamed for causing most cases of coronary artery disease (CAD):
- Low Density Lipoprotein Receptor (LDLR)
- Apolipoprotein (APOB)
- Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9)
FH can be diagnosed through clinical criteria, but experts recommend genetic testing to provide a definitive diagnosis, proactive family screening, timely initiation of therapy, and improved risk management.
“In this era of precision medicine, genetic testing is an important tool to identify people at high risk for FH and guide the management of their LDL cholesterol to reduce long-term morbidity and mortality from early and aggressive CAD,” said Daniel J. Rader, MD, chair of the department of Genetics in the Perelman School of Medicine at the University of Pennsylvania, Chief Scientific Advisor of the FH Foundation and co-author of the paper. “Physicians should entertain the diagnosis of FH in their patients who have a family history of early heart disease and/or high LDL cholesterol, and consider offering a genetic test in those who may have FH.”
While genetic testing has clear benefits, it is possible to diagnose an individual with the condition without its use. Further, a negative genetic test does not completely eliminate the possibility of the presence of FH. The panel’s conclusion is best summarized as patients with a family history of early heart disease and substantially elevated LDL cholesterol should be screened for FH and then offered a genetic test to confirm the diagnosis.
SOURCE: FH Foundation
