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Experts say people with a family history of high cholesterol should get tested. Sergey Narevskih/Stocksy
  • Researchers say genetic testing can help identify people with a family history known as familial hypercholesteremia.
  • They say that identifying the condition can help medical professionals prescribe treatments and interventions.
  • Experts recommend that people with this family history have their cholesterol levels checked regularly.

Routine screening for genetic predisposition to high cholesterol could help steer people to potentially life-saving interventions.

That’s according to a new study in which researchers note that people with familial hypercholesteremia have high cholesterol that often can’t be explained by common risk factors such as diet, inactivity, and obesity.

Unlike other people with elevated triglyceride levels in their blood, people with familial hypercholesteremia can’t lower their “bad” cholesterol simply by making dietary or behavioral changes.

However, statins and other medications can help people with this condition, which affects about one in every 250 people.

“The two most effective classes of medications in this population are statins and PCSK9 inhibitors,” Dr. Cheng-Han Chen, an interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in California, who wasn’t involved in the study, told Medical News Today.

Before they can start on these medications, however, people with familial hypercholesteremia need to be identified, according to the researchers from Intermountain Health in Salt Lake City, Utah.

“Most of these patients already had tests that showed they had high cholesterol,” said Stacey Knight, PhD, a cardiovascular and genetic epidemiologist at Intermountain Health, in a press statement. “Our findings show that we should be genetic testing people who have unexplained high cholesterol, so we can aggressively treat it and cut down their risk of having a major heart event.”

The researchers presented their findings at the American Heart Association’s Scientific Sessions 2023 in Philadelphia.

The research hasn’t been published yet in a peer-reviewed journal.

Knight and her colleagues reviewed the records of more than 32,000 people whose genes had been sequenced via the HerediGene Population Study.

They reported that 157 of the study subjects had a variant of the LDLR gene associated with familial hypercholesteremia.

Researchers then grouped the people with the familial hypercholesteremia gene into three groups: those with no prior diagnosis; those with a diagnosis after a major cardiovascular event such as a heart attack, heart failure hospitalization, stroke, periphery artery disease, or carotid artery disease; and those with a diagnosis that took place before any cardiac event occurred.

The study revealed that people who were screened and diagnosed with familial hypercholesteremia prior to having a major cardiac event had more testing of their LDL (“bad”) cholesterol levels, were more likely to be on statins or other cholesterol-lowering medications, and had experienced a significant change in the LDL levels in their blood.

“I think this might be proof that knowledge is power,” Knight told Medical News Today. “When a patient gets a proper diagnosis of [familial hypercholesteremia], we can take steps to treat them and reduce major cardiovascular events and death.”

These study subjects were only slightly less likely to have had subsequent major heart events, the researchers said, but Knight noted, “Many of this study’s major cardiovascular events occurred before the new medication options for [familial hypercholesteremia] that are now available. I anticipate that these medications and others being developed will help decrease these events significantly.”

Notably, people who were diagnosed with familial hypercholesteremia only after a major cardiac event had higher death rates than those who had been diagnosed earlier.

“Referring these patients for genetic counseling could lead to intervention through medication, and lead to better quality of life, and save their lives as well as could result in additional testing and early intervention for their family members,” said Knight.

She noted, however, that currently no population-based genetic screening for familial hypercholesteremia exists in the United States, “though organizations are working on developing these — the Family Heart Foundation, for example — to deploy within health centers.”

As more gene mutations associated with diseases are identified, opportunities to intervene at earlier stages of diseases such as familial hypercholesteremia will increase, too, said Chen.

“[Familial hypercholesteremia] is a winnable battle, and improving our ability to make a genetic diagnosis of this condition is a first step toward addressing this high risk condition in our population,” Elizabeth Jordan, a cardiovascular genetic counselor and associate professor of internal medicine at The Ohio State University Wexner Medical Center who wasn’t involved in the study, told Medical News Today.

As the study indicated, some, but not all, people with familial hypercholesteremia do get screened.

“If there is a family history of [familial hypercholesteremia], or strong family history of cardiovascular diseases, we recommend screening for [familial hypercholesteremia] by checking LDL levels as young as two years old,” Dr. Irman Forghani, the director of genetics at Mount Sinai Medical Center in Florida who wasn’t involved in the study, told Medical News Today.

“Any individuals with elevated cholesterol level should have genetic counseling and to learn about their options for genetic testing,” she added.

Statin medications, such as atorvastatin and rosuvastatin, work by inhibiting the production of cholesterol in the liver, explained Dr. Rigved Tadwalkar, a cardiologist at Providence Saint John’s Health Center in California who wasn’t involved in the study.

He said PCSK9 inhibitors such as evolocumab and alirocumab are a newer class of drugs and increase the liver’s ability to remove LDL cholesterol from the bloodstream.

Another new drug, inclisiran, works by inhibiting PCSK9 production, Tadwalkar told Medical News Today, while ezetimibe reduces cholesterol absorption in the intestines.

All of these drugs have been shown to be effective in treating patients with familial hypercholesteremia, he said.

The American Heart Association and other professional societies advise that all adults with familial hypercholesteremia undergo risk assessment, and receive lifestyle counseling, have close monitoring of LDL levels, and starting lipid lowering medications, noted Forghani.

“Additionally, it is advised that all patients undergo imaging to assess the extent of atherosclerotic changes and response to treatment,” she said. “There are targeted therapies for patients with specific gene mutations and treatment guidelines for patients who do not respond well to initial treatments.”

Tadwalkar noted that there actually are two forms of familial hypercholesteremia: heterozygous FH (HeFH) and homozygous FH (HoFH).

“In HeFH, an individual inherits one defective gene copy responsible for regulating cholesterol metabolism, typically from one parent. This form of FH is more common, affecting about 1 in 250 individuals,” he said. “HeFH is generally more manageable with standard therapies. On the other hand, HoFH is a more severe form of [familial hypercholesteremia], where the individual inherits two defective gene copies for cholesterol regulation, [one] from each parent. This results in even higher LDL cholesterol levels and a much greater cardiovascular risk. Fortunately, this is rarer, occurring in about 1 in 1 million individuals. It is particularly challenging to treat due to the more profound genetic mutations.”