Diagnosing HoFH Remains a Challenge and Early Detection Is Essential

Seth J. Baum, MD, Chief Medical Officer of Flourish Research and the Vice Chair of the Board of the Family Heart Foundation, talks about the importance of educating pediatricians on homozygous familial hypercholesterolemia (HoFH) so they can identify and refer patients earlier.

Question:

Could you discuss the challenges in diagnosing and managing HoFH?

Seth J. Baum, MD:

There are a lot of challenges in diagnosing and managing HoFH. I think the most important one is that this is a genetic disorder and the first people to see these patients are the pediatricians, and unfortunately the pediatricians don’t have significant training in lipids and cardiovascular disease. They’re not thinking along those lines, even the pediatric cardiologists, and I’ve spoken with several of them to confirm this. In their training they have very, very limited exposure to lipid abnormalities. Some people say it can be a month at most in a program, so they’re not… When they go into practice in general, and there are exceptions obviously, but in general they’re not really equipped to identify adequately and manage patients with homozygous FH. That’s far and away our biggest stumbling block, and we need to do everything we can to reinforce the screening procedures we have in place, the screening guidelines, so universal screening between 0 and 2, universal screening 9 to 11, those guidelines to be able to pick up these patients, to identify these patients at a very young age.

Then once you’ve identified someone, so you need an index of suspicion first. You need to screen, then you need the index of suspicion, and you go, “Aha, I see this patient with a ridiculously high LDL. What’s going on?” Then you need to refer to a lipid specialist or even an adult cardiologist who has preventive cardiology expertise. I am often referred kids because the pediatric cardiologists or the pediatricians are uncomfortable with identifying what the disorder is and then managing it. I’ve treated someone as young as just I think 16 or 18 months of age, and I’m not a pediatrician. We in adult cardiology, adult lipidology, need to be a little more flexible and treat these kids to some extent in conjunction obviously always with the pediatrician, but we need to do it if the pediatrician is uncomfortable. Then ultimately, and I’ve worked with some pediatric cardiologists who ultimately frankly develop an interest and an expertise in the area, and then they’re on their own and then they become the regional expert in FH. That’s a very gratifying thing to happen, and it has happened.

I would say that those are our biggest constraints or problems, the identification among pediatricians because they’re the ones seeing them and then the treating those patients again because they’re in the pediatric world. It does unfortunately extend beyond that, though, because I’ve seen this in adult medicine as well where patients will have markedly elevated LDL and sort of sit in a practice for a while without the diagnosis of HoFH having been made. It’s more like, “Oh yeah.” The physician will say, “Yeah, we think this is probably a genetic disorder or family issue.” But then they don’t make that very, very important diagnosis of HoFH. It’s important not just for the patient. It’s important for the family because once you identify someone with homozygous FH or heterozygous FH, we should always cascade screen. We should always look at all of the first-degree relatives and then beyond if necessary to identify other individuals who have familial hypercholesterolemia and might not be getting the treatment they need.

Question:

Are there any emerging therapies or research advancements in the field of HoFH treatment?

Seth J. Baum, MD:

I would say the greatest advance we’ve had of late was evinacumab. There are other similar agents in the pipeline and then there are similarly related compounds. There are some things in the pipeline. Evinacumab has done a wonderful job. Then not now, but way down the road I’m imagining that we’ll have some genetic solutions here through gene editing, but certainly that’s not coming soon. The first thing that’s going to happen will be in heterozygous FH, and homozygous is going to be a while down the road. There are a few things in the pipeline, but I don’t see anything right now extraordinary beyond the evinacumab ANGPTL3 inhibition.

Question:

How important is early detection and intervention in HoFH, and what strategies can healthcare providers use to improve identification and management of this condition?

Seth J. Baum, MD:

It’s essential that we identify early and manage early. Again, time is plaque. Elevated LDL causes plaque. When you have plaque, you’re at risk for heart attack, stroke, peripheral arterial disease, death. These children with homozygous FH can have cardiovascular events well before they’re 10 years old, so it is absolutely essential to do this quickly. We need to develop a better comfort level among the pediatricians and pediatric cardiologists with regard to lipid management. We need to adhere to the guidelines of universal screening between 9 and 11 and around 20 years old. If we haven’t captured the individuals through targeted screening when they’re newborn to 2 or between 2 and 9, let’s say, then at least we have another opportunity to identify them, but the targeted screening between newborn and 2 is really very important so the pediatricians need to understand the family history. Often, visits are brief, everybody’s so rushed in medicine now, unfortunately, that maybe the family histories aren’t being taken adequately as a consequence of time burden. I think these are the ways we can address and improve our identification of these patients.

Question:

Can you discuss the role of genetic testing and familial screening in identifying individuals at risk of HoFH?

Seth J. Baum, MD:

Genetic testing, I think, has a very important role in screening or identifying individuals with homozygous FH. When mutations are identified, it’s very valuable because we can then, frankly, screen family members using those mutations to see whether they have either heterozygous or homozygous FH. We also know, at least in heterozygous FH and I believe it’s likely the same in homozygous FH, that when we identify a mutation, risk is actually higher. It is valuable. The downside of genetic testing is if people are misled. If for example they identify only 1 mutation and they say a patient is heterozygous FH and not homozygous but clinically they’re homozygous, for example, they have a baseline untreated LDL of 560, that’s a patient with homozygous FH. If you identify only 1 mutation, then you’re just missing the other one. We have to be very careful and not limit the therapeutic options available, such as lomitapide and evinacumab, which are available only to HoFH patients. In somebody who is clinically homozygous FH, that person should be eligible as well.

Question:

Do you have any final remarks to share?

Seth J. Baum, MD:

I would just reiterate that it is so important to identify these individuals early on in life and to treat them as aggressively as possible. We have to have a sense of urgency here because, as I’ve said, time is plaque, and what happens after plaque? Heart attack, stroke, potentially death. These are children. It’s a genetic disorder so children have this and young adults. We’ve shown from the Family Heart Foundation publications through the CASCADE FH Registry that we’re diagnosing these people too late; we’re treating them inadequately, so we need to do much, much better. We need to avoid these missed opportunities to stave off heart attacks. These are dramatic events. These are not subtle things, and we do have the opportunity to make a difference.