The US is Frequently Missing the HoFH Diagnosis

The US is Frequently Missing the HoFH Diagnosis

Breaking Down the Latest Family Heart Foundation Research on HoFH in America

new study from the Family Heart Foundation is the largest look at how individuals with homozygous familial hypercholesterolemia (HoFH) are being treated in the United States today. 


HoFH is the most severe form of the common genetic disorder, familial hypercholesterolemia (FH). It causes extremely high levels of low-density lipoprotein (LDL) cholesterol from birth. This rare disease affects 1 in 300,000 people around the world. 


Let’s break down this new research:

1. We gathered large amounts of information from two databases.

To begin, the Family Heart Foundation team looked at data in the CASCADE FH® Registry. This Registry was created in 2013 by the Family Heart Foundation. It includes characteristics, treatment patterns, and clinical events. This data is submitted by healthcare providers treating individuals with FH.


In that database, there are 67 children and adults who are clinically diagnosed with HoFH. Forty-three of them had genetic tests confirming their HoFH diagnosis.


Then, the team took the characteristics of those with genetically confirmed HoFH and searched the Family Heart DatabaseTM. This database is a combination of anonymous insurance claims with diagnosis codes, procedure codes, prescription data, and lipid values. This helped the team identify those who looked like people who have HoFH in a real-world setting.

2. Children and adults with HoFH have extremely high LDL cholesterol. Many are diagnosed late, and as a result, have very early, aggressive heart disease.

Based on data in the CASCADE FH Registry, the children with HoFH had much higher LDL levels than the adults. The median (middle value) untreated LDL level in children was 776 mg/dL and for adults, it was 533 mg/dL. The higher level in children tells us there are probably children with less severe HoFH who are not spotted in childhood. Instead, they are found as adults, generally when they have a cardiac event.


For context, the American College of Cardiology and American Heart Association Cholesterol Guideline recommends treating LDL cholesterol to reach less than 100 mg/dL for those without cardiovascular disease, and 70 mg/dL for those with cardiovascular disease. The untreated LDL levels we uncovered are more than five to almost 8 times what the guideline recommends.


When they were enrolled in the Registry, 44% of the children and 78% of the adults with HoFH already had cardiovascular disease. The median age of developing cardiovascular disease was 9 years old in children and 31 years old in adults. Again, this suggests that only the most severe children are being found in childhood. 

3. Most adults and children with HoFH are not at their LDL goal and need more treatment.

The team then looked at the follow-up data in the CASCADE FH Registry. After these individuals were treated with 3-6 of the available lipid-lowering therapies in specialty clinics, adults saw a 72% drop in LDL cholesterol, and the children had a 61% reduction.


However, that was still not enough. This is a dramatic improvement, but 68% of the adults and 75% of the children had not brought their LDL cholesterol down to the Guideline-recommended level.

4. Outside of specialty care, people with HoFH are largely undiagnosed and undertreated, leading to irreversible heart damage.

When the team took these criteria to the 81 million Americans in the Family Heart Database with lab data available, they identified 277 individuals whose characteristics were the same as people in the CASCADE FH Registry who had HoFH. Their median LDL cholesterol level was 444 mg/dL.

  • Only 26% of these individuals had an FH diagnosis.
  • 84% of these individuals were under 50 years old.
  • 20% of these individuals already had heart disease.

5. Among people in the Family Heart Database, lipid-lowering therapies are not being used enough.

In that same Family Heart Database information, it was concerning to see 40% of these individuals who likely have HoFH were on no lipid-lowering treatments – not even a statin


Adults and children with HoFH need early and aggressive treatment with multiple medications and therapies. The data tells us that’s not always happening. Forty percent of them are not on any treatment, 19% are on high-intensity statins only, 14% are on a PCSK9 inhibitor, and 28% were on some other forms of lipid-lowering treatment. Only 5% were on lomitapide, a treatment that is FDA-approved specifically for people with HoFH.


This study was conducted before the FDA approval of evinacumab, an additional treatment specifically for adults and children with HoFH. A follow-up study is needed to determine if more people with HoFH reach recommended LDL levels with the availability of evinacumab.

6. We have an urgent need for universal lipid screening in childhood.

Our research shows that HoFH is systemically underdiagnosed and undertreated. This rare disease is a challenge to treat, but it starts with a diagnosis. 


One critical way of changing this and saving more hearts is universal pediatric lipid screening. Currently, the American Academy of Pediatrics recommends all children have their cholesterol checked between the ages of 9 and 11 and again between ages 17 and 21. If one or both parents have FH or a family history of heart disease, their children should have their cholesterol checked by age 2. 


Our research suggests those guidelines are being overlooked, so we are losing valuable time treating this aggressive disease. This is how we see people with undiagnosed HoFH having heart attacks in their 20s and 30s and children having heart disease as young as age 4.


The outlook for adults and children with HoFH today is very hopeful. A combination of several available treatments can dramatically reduce LDL cholesterol. This includes medicines specifically for people with HoFH. We just have to take the steps to make the changes that will save more families and more hearts. 

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