The FIND FH Initiative

Who Is at Risk?

Familial hypercholesterolemia (FH) is often diagnosed using lab results and family history. High levels of LDL cholesterol that do not reduce to normal levels following alterations to one’s lifestyle and diet are common among those diagnosed with FH. Additionally, those with FH often have a family history of high cholesterol and early heart disease and/or heart attacks.

Individuals with family members that are diagnosed with FH may also have this condition. Because FH is a genetic condition, it can be inherited. The children of those with FH have a 50% chance of inheriting the condition. In the rare case that both parents of the child have FH, the child can have a more severe form of FH called homozygous familial hypercholesterolemia (HoFH). Therefore, it is crucial to screen first degree relatives (parents, siblings, and children) when one family member is diagnosed.

Symptoms of FH

Some individuals with FH may display physical symptoms due to high levels of LDL cholesterol in the bloodstream. These include the following: A white or gray arc near the colored part of the eye Yellowish areas around the eyes Bumps or lumps around the knees, knuckles, or elbows due to cholesterol deposits under the skin Painful Achilles tendon or tendons in hands due swelling of tendons from cholesterol deposits

Treating FH

Due to a genetic mutation, individuals with FH have abnormally high LDL cholesterol levels. As a result, lifestyle interventions, such as alterations to exercise and diet patterns, cannot alone adequately lower LDL levels to a normal range. Instead, a combination of lifestyle changes and medication are required to significantly lower LDL cholesterol levels. Treatment usually involves statins, which are drugs that lower cholesterol, and injectable medications called PCSK9 inhibitors, which help remove cholesterol from the blood. When done together, regularly taking medication, maintaining a heart-healthy diet, and exercising regularly can greatly reduce the risk of having a heart attack or stroke.

Why FH Matters

Familial hypercholesterolemia (FH) is an autosomal dominant condition that affects 1 in 250 people worldwide, characterized by a genetic mutation that affects how cholesterol is regulated in the body. This allows high amounts of low-density lipoprotein (LDL) to accumulate and cause atherosclerosis. As a result, young adults and even children with this genetic condition can face complications such as heart attacks and strokes.

Though individuals with untreated FH can have up to a 20x increase in lifetime risk of heart disease when compared to the general population, estimates show that only 15-20% of these patients have been diagnosed. Further still, current data suggests that over 25% of documented FH patients have already progressed to heart disease by the time this diagnosis is made. With targeted early interventions, however, FH patients can reduce their risk of heart disease down to that of the general population. Caregiver awareness about the dangers of FH and its early presenting signs can therefore be pivotal in reducing lifetime risk for not only the patient, but also their family members.

Diagnostic Criteria

Though FH is a genetic condition, it is possible to diagnose this condition based on clinical criteria alone. Clinicians should consider a FH diagnosis if the patient:

• Presents with a family history of premature coronary heart disease (CHD) (at age <55 in males, <65 in females)
• Has high LDL-C without current treatment** (if ≥20 years old, must be ≥190 mg/dL; if <20 years old, must be ≥160 mg/dL) **If currently being treated, LDL-C levels must be >124 mg/dL In addition, the presence of xanthomas, corneal arcus or xanthelasmas before age 60 are suggestive of FH.

Though clinical diagnoses are more common, genetic testing identifying mutations in the LDLR gene, apoB gene, or PCSK9 gene are available and can confirm the diagnosis. However, treatment decisions are ultimately made based on phenotype, not thegenetic testing result.

Once an individual with FH has been identified, lipid testing with or without genetic testing for all first-degree relatives should be strongly encouraged.

Treatment

Due to the familial nature of this disease, early and aggressive intervention is key. Pharmacological therapy targeting LDL reduction, such as statins, ezetimibe, bile acid sequestrants, and PCSK9 inhibitors should be considered. For those with heterozygous FH, therapy should be initiated between the ages of 8-10, and statin therapy can be initiated at time of diagnosis. In addition, physicians should engage in discussion with patients about how to reduce risk through lifestyle modifications, such as exercise and a heart-healthy diet.

Ultimately, the target levels of LDL-C for adults with FH is a 50% reduction in pre-treatment LDL-C with:

• LDL-C < 100 mg/dL without coronary heart disease and/or other factors
• LDL-C < 70 mg/dL with coronary heart disease and/or other factors