Early Screening for Familial Hypercholesterolemia Can Save Entire Families From Premature Cardiovascular Disease

With so much ground to cover in a well-child visit, cholesterol may not be at the top of your mind. After all, cardiovascular disease doesn’t usually develop until after age 55 in men and age 65 in women. However, many young patients have elevated LDL cholesterol levels caused by familial hypercholesterolemia (FH). If proper screening measures aren’t taken, the health of the patient and their entire family could be in jeopardy.

Cause and indicators

FH is an inherited disorder caused by an abnormal mutation of one or more of the genes responsible for cholesterol metabolism. Instead of processing LDL in the liver properly, the body has increased deposits in the blood vessels causing cholesterol plaques. Patients with a long history of elevated LDL can begin developing significant atherosclerotic cardiovascular disease (ASCVD) as early as age 30 in men and age 40 in women.

“In addition to elevated LDL levels, patients with FH also tend to have low HDL levels,” explains Christina Fink, MD, pediatric cardiologist and head of the Lipid Clinic at Cleveland Clinic Children’s. “A first-degree relative with high LDL is also a probable indicator of FH. However, young patients may not have a family history of high LDL, especially if the gene mutation for FH starts with the child.”

According to the Journal of the American Heart Association, FH affects about 1 in 220 individuals in the U.S. It can be diagnosed as early as the first few years of a patient’s life.

Patient registry study

The Journal of Pediatrics recently published the results of a study that analyzed the enrollment characteristics of young patients in a national FH registry. Key highlights of the study include:

• Baseline characteristics: The average LDL was 175 across all age groups. HDL levels were very similar among the age groups.
• Treatment patterns: The most common lipid-lowering therapy involved statins, especially in patients age 10 and older. About 25% of children over age 10 were not being treated.
• Treatment goals: The primary goal was to get the LDL level under 130 or reduce the LDL levels by at least 50%. Of the children who were on lipid-lowering therapy, only 30% achieved the recommended LDL reduction. The older children tended to have lower LDL levels since many of them were in treatment.
• Risk factors: The majority of patients had other risk factors, the most common of which was low HDL levels. A family history of premature cardiovascular disease was also a fairly common risk factor.

“Collecting data for FH patients provides useful baseline data to help recognize disease characteristics and explore patient profiles,” notes Dr. Fink. “This study also highlights the importance of screening to facilitate early intervention in order to prevent negative outcomes.”

Clinical management

When it comes to managing high cholesterol, lifestyle plays an important role. “When we have patients with LDL levels around 190, we start by analyzing their diet and exercise history as well as their screen habits,” explains Dr. Fink. “We typically give them three to six months to improve to see if they can get their LDL levels below 160 naturally.”

“Young patients who are willing to make changes might be able to lower their LDL by 20%, which could postpone treatment for several years as we continue to monitor their condition,” Dr. Fink reveals. “But if you have FH, lifestyle changes typically will not be enough to get you to the recommended threshold for your age group. Plus, LDL levels tend to creep up over time and eventually require medication.”

Statins are the most common form of lipid-lowering treatment and have been shown to be fairly safe and well-tolerated in children. “We can treat children with FH as early as age 8, when the LDL concentration is greater than 250. But we typically wait until age 10,” says Dr. Fink. “It’s important for family members to comply with medication recommendations and overcome any stigma they may have about statins.”

Screening recommendations

FH is diagnosed with a simple blood test. In harmony with the national guidelines, Dr. Fink recommends the following best practices for screening at well-child visits:

• If there’s a family history of high LDL or early ASCVD, especially in a parent, begin screening patients at age 2.
• Perform universal cholesterol screening for all patients age 9–11 and 17–21.

“If we screen children at age 9 versus age 2, we’ll still catch the LDL problem,” explains Dr. Fink. “But if we can identify these children sooner, we can do cascade screening for the whole family and potentially save multiple people from premature ASCVD.”

“Even if a child looks otherwise healthy, it’s important to ask parents about their own health issues during well-child visits and investigate them promptly,” Dr. Fink emphasizes.

Genetic testing

If genetic testing is desired, Dr. Fink recommends consulting a genetic specialist as well as a genetic counselor. The counselor can help interpret test results and recommend next steps. “While it can be helpful to identify the specific genetic cause of FH, the most important thing you can do is biochemically screen your family members for high LDL levels,” she says.

Referral to a specialist

If your patient has an LDL greater than 190, refer the patient to a lipid specialist. If your patient has an LDL around 160 or 170, it may be helpful to refer the patient to a specialist when diet and exercise are unable to bring levels down to less than 130.