What is Familial Hypercholesterolemia? A discussion with Katherine Wilemon (FH Foundation) & Dr. Jill Hagenkord (Color)

On this episode of Sequenced, we talk to Katherine Wilemon, Founder and CEO of the FH Foundation, and Dr. Jill Hagenkord, Color’s Chief Medical Officer, about Familial Hypercholesterolemia (FH), an inherited high cholesterol disorder. Katherine and Dr. Hagenkord discuss what differentiates FH from garden variety high cholesterol, why FH is underdiagnosed in the U.S., and how an FH diagnosis can impact an individual’s family members.

The FH Foundation is a patient-centered nonprofit organization dedicated to research, advocacy, and education of Familial Hypercholesterolemia (FH). Their mission is to raise awareness and save lives by increasing the rate of early diagnosis and encouraging proactive treatment.

We’ve posted complete transcript of the podcast below. You can subscribe to Sequenced on Apple Podcasts, SoundCloud, Stitcher, and Google Play.

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Moderator: We’re going to talk about cholesterol. We all know that there is good cholesterol and bad cholesterol and there’s a level of each that we should shoot for according to the latest medical research to fend off heart disease and stroke. What you may not know is that the vast majority of the cholesterol circulating in our blood doesn’t come from our diet but is produced by our bodies themselves and in particular our livers. For some people with an inherited disorder, their livers can’t remove excess levels of the bad cholesterol which can lead to premature heart disease.

That inherited disorder is familial hypercholesterolemia or FH. One in 250 people have FH and most don’t even know it. That was the case for Katherine Wilemon, who founded the FH Foundation to shine a light on the disorder. Katherine joins this segment of the podcast to discuss FH and her own experience trying to find the answers. Katherine, welcome.

Katherine. Hi, Michael, thank you for having me.

Michael:. Also joining us is Dr. Jill Hagenkord, Color’s Chief Medical Officer, and a Molecular Genetic Pathologist. Jill, welcome.

Jill: Hi, thanks for having me.

Michael: Let’s start at the beginning. Katherine since you’ve gone through this personally.and you started the foundation, tell us what is familial hypercholesterolemia or FH?

Katherine: For one thing, it’s hard to say. FH is an autosomal dominantly inherited genetic condition that inhibits a person’s ability to break down the cholesterol that is normally in their bloodstream which leads to high cholesterol from birth and overtime often leads to premature cardiovascular disease.

Michael: This is something that you have from birth. This is not when people’s cholesterol levels kick in later in life. But with FH, kids have it, babies have it.

Katherine: Exactly. Actually, the American Association of Pediatrics recommends that if there’s a family with FH that all of the children be screened by the age of two when those cholesterol levels are stabilized so it can be recognized that early. It’s that protracted exposure throughout someone’s lifetime that leads to significant risk.

Michael: Jill — 1 in 250 people have FH. Can you put that in some kind of perspective? I mean that’s sounds in a room of 250 people, that’s not that many people. How does that compared to other inherited disease?

Jill: Well, compared to other inherited diseases, it’s one of the more common ones. Let’s look at it in terms of people with high cholesterol. 74 million people in the United States have high cholesterol or about one and third of all adults have high cholesterol. 1 in 50 of those people have FH and almost none of them know it. We have diagnosed less than 1% of familial hypercholesterolemia in the United States. We’re treating everybody the same as if they all have garden-variety high cholesterol.

You mentioned earlier that it is due to bad lifestyle choices in your 30s, and 40s, and 50s as opposed to being born with high cholesterol and having that exposure since birth. When physicians counsel people with high cholesterol they counsel them all the same. Right? Without taking into account that 1 in 50 of these people have been exposed since birth and the other 49 have increased their cholesterol levels over time. And then they treat them both the same.

They’ll say, “Go change your diet and your lifestyle and see if that works.” With FH that really is ineffective. You almost always have to go to some kind of medication to get to target LDL levels. Once they’re identified as having FH you want to put them on a higher dose, higher potency statin right away and then as necessary go quickly to a double and even triple therapies. For people with garden-variety high cholesterol, you try to start with diet and exercise and then start them on a lower dose, lower potency statins.

Michael: The mechanism of high cholesterol of people with FH is the liver not being able to remove the excess LDL. That’s why diet or exercise are not necessarily the answer to the disease.

Jill: It’s hard to compensate for that physiologically.

Michael: It’s stunning that it’s as common as it is, most people who have FH don’t even know it. I have two questions…how common it is but also why don’t those people who carry this disorder even know about it?

Katherine: It really is shocking how underdiagnosed it is. If you think about cystic fibrosis which everyone has heard of, Familial Hypercholesterolemia is 50 times more common. But it’s literally invisible and has been to the medical community. One of the things that we discovered as an organization was that there was no specific ICD, 9 or 10 code that differentiated FH even though we have understood that this was a distinct condition.

Michael: Meaning even if it was diagnosed when it was marked down in some medical record there was no distinction, is that what you’re saying?

Katherine: Exactly, Michael. There was a code for pure hypercholesterolemia which included a lot of different varieties and it was not very user-friendly. It was based on old Fredrickson’s model of how you differentiate different kinds of lipid disorders. But there was no specific code for Familial Hypercholesterolemia. This was part of the problem and the FH Foundation applied to the CMS to get a distinct code for Familial Hypercholesterolemia, because it’s so important in terms of that patient’s care, as Jill alluded to earlier. We know that children with FH if they live in the same household they have a sibling who has FH and a sibling who doesn’t have FH.

By the time those children are 11 years old you can consistently see plaque in the arteries of the affected child. This is a disease that begins very early in life and really needs to be differentiated and treated differently than high cholesterol. It poses an entire different risk. But to answer the question of why it’s been so underdiagnosed, it’s a little bit of a head-scratcher honestly. But I think that the medical community, there’s a construct that if you are treating the LDL level you don’t need to differentiate whether or not it’s genetic. And quite frankly, the data says that that’s not true.

Michael: Jill, how do you view this as a person who studies genetics.

Jill: I agree with Katherine. It’s a head-scratcher. The medical community, and even to this day even with new data, high-profile papers in science and other prominent journals coming out looking at FH, the medical community whether it’s cardiologist or general practitioners have a lot of resistance to even thinking about FH and even when I bring it up to them they have a tendency to say, “Oh, it doesn’t matter, high cholesterol is high cholesterol. I’m just gonna manage the symptoms, you know, the high cholesterol. It doesn’t matter if it’s genetic.”

And I’m not sure if that’s just a matter of physicians historically not getting much genetic education in medical school or if it’s just a matter of 20 years ago when I went through med school and we got very little training in genetics. But what little we did gave us kind of inaccurate snapshot of the hyperlipidemia syndromes. We just know so much more now. But I think it’s one of the things that the FH Foundation has been working really hard to do is try to put out a call to action to the primary care docs and the cardiologists.

Michael: If you’re a physician listening or if you’re a person listening who’s not a physician, I mean tell us why this does matter. I mean the distinction between high cholesterol whether it’s genetically inherited or not, why does FH matter and why is it a different kind of animal compared to other high cholesterol?

Jill: Number one, familial hypercholesterolemia has a dramatically different risk profile that you need to describe to your patient than a garden-variety high cholesterol. So even when you’re just talking about what is your cardiovascular risk, it’s a very different conversation for those two subsets. Number two, the way that you manage the patients, the medications that you give them and kind of the cadence at which you give it is different for those two patient populations.

Number three, we know that if you give somebody a genetic diagnosis of FH they’re 94% compliant with their medication after getting the genetic diagnosis as opposed to somewhere in the 40% if they don’t have a genetic diagnosis, and that’s a huge impact on compliance including the genetic information.

Michael: Do you have any sense of why that compliance is so dramatically different?

Jill: I can speculate. There’s a handful of studies out there looking at stuff like this and just that in my career having worked kind of, you know, in the area of consumer genomics. That when you give somebody a piece of genetic information about themselves, it creates this health awareness moment or it makes you an activated patient. It makes you a little bit more receptive to health information and recommendations that your healthcare provider may be giving you.

It also inspires you to take stock in your own health history and ask questions about your family’s health histories. I could just call it a health awareness moment. It almost has this halo effect. It doesn’t matter necessarily even what the genetic result was, you’re still kind of seeing that same effect.

Katherine: Well, if I may, I think there’s another point of why you need to differentiate as a healthcare provider for FH. Each child of an individual with familial hypercholesterolemia, it’s a flip of a coin whether or not they also have inherited FH. It’s a 50–50 chance as it is with each first-degree relative. This is a clear case for family cascade screening. If we’re going to start focusing increasingly on leveraging these tools like the explosion in genetics then we need to look at how it factors into better health and not just treating illness but preventing it.

That’s why I think familial hypercholesterolemia is such an exciting story because we can now know who is at risk decades before we see clinical signs of pathology. With easy and quite frankly oftentimes inexpensive, very safe therapies like low-dose statins in children, we can almost normalize their risk curve. Remember, they have a 20-fold risk if left untreated of having premature coronary heart disease. We can almost normalize it if we treat it in at the end of their first decade of their life, and that’s incredible.

Michael: Katherine, let’s talk about your own experience with this because you founded a foundation to call attention to this. When did you get diagnosed and even how did you get a diagnosis and how did you get there?

Katherine: So let’s start in the middle. At the age of 39, I found myself in a cath lab and with a physician who despite the results on a treadmill test was still had some trepidation or was a little bit dismissive of why I’d be in there. And said, “Why do I have a 39-year-old woman lying on my table?” And the next thing he said to me as he was doing the intervention was, “Oh, my god, you’d had a heart attack.” And, when it was all over he told me that I had the arteries of a 70-year-old.

That really made the level of risk that I had faced exceedingly concrete but I didn’t fully understand why this had happened to me. I’d always known since I was 15 years old that I had LDLs that ran above 300. I’d been told that I’d probably had inherited high cholesterol but that’s not the same thing as giving someone an explicit diagnosis with a roadmap of what they need to do to manage that risk. It took me a couple of years after my event to actually find a physician who is an endocrinologist who could fully explain to me the condition. The moment he said, “You need to have your daughters checked,” I had an epiphany that there was so much work to be done. And started to go and speak around the country and have the honor speaking internationally as well because there’s some other countries that we can learn a lot from who’ve done a great job in diagnosing familial hypercholesterolemia. There’s just a few in Northern Europe that have diagnosed about 75% of their population, but most of the world, unfortunately, is doing the same abysmal job that we’re doing. And it’s not hard to diagnose FH and it’s not hard to treat it.

Michael: Those countries in Northern Europe, are their populations more genetically predisposed to FH and is that why it’s more of a thing there or what can we learn from them and what can we do that models their behavior?

Katherine: In the Netherlands, there is some sense that there may be a slightly higher predisposition for familial hypercholesterolemia but it’s not really a founder population. But the government who owns the risk of someone from birth to death as a single payer saw that this was an opportunity to intervene at a population level to improve health. They embarked on building a registry and a family screening program for the entire country. Now, it’s a very, very small country, with a centralized medical system.

But it was that vision and that impact that they had in basically a decade that encourages me. For example, the FH Foundation started a National Registry because data drives policy, it drives awareness, it drives quality improvement. Right now, Jill and I are both working with the Institute of Medicine and the CDC to basically embark on figuring out how can we bring family screening to the United States. Because it’s very complicated in a fragmented healthcare system with HIPAA laws that don’t allow us to reach out directly to family members.

Michael: Katherine, you mentioned cascade testing and Jill I want to bring you in this. Tell us about cascade testing and how does that encompass FH and other genetic disorders?

Jill: Cascade testing is just another way of saying testing of at-risk family members in the context of an inherited disorder like familial hypercholesterolemia because genetic diseases are family diseases. Once you identify the proband or the primary person in the family who is affected you would want to test people and their immediate family as well because 50% of them are going to be positive. As Katherine alluded to earlier, in the United States the construct of our healthcare system is not set up to do family medicine or to take care of a family. It’s set up to take care of a person.

Michael: The individual, right.

Jill: The electronic health record is setup to optimize for billing and not necessarily for patient management. Then we’ve got laws that actually prevent a physician from reaching out to at-risk family members and letting them know their risks. We’ve got a number of barriers in the United States that prevent us from being very efficient at all in reaching out in this genetic diseases that affect families. That is one of the reasons why our diagnosis rate of FH is so abysmal. That said I’m actually kind of excited to see genetic testing laboratories are now, there’s a couple of them who’ve got it implemented.

And I’m sure others will follow. They’re actually in a position in the United States where they can start to solve this. By offering family testing programs through the laboratory website, and using software tools, you can enable the proband to become the family champion. And then easily helping populate emails that he or she can send to their at-risk family members with all of the appropriate medical information at an 8th-grade level and an easy access for those people than to come back and get tested. I’m optimistic that in the next few years we’ll see that trend catch on and that it’ll actually be much more efficient than what we’re currently doing.

Michael: It seems like that receiving a message from a family member as opposed to a medical testing company or even your physician might drive you to pay more attention.

Katherine: We certainly see in the community that people feel incredibly empowered by having a concrete diagnosis. Most people know when something is awry with them even if they don’t have a name for it and they certainly know their family histories. And it’s amazing to hear stories again and again, a family is riddled, for example, with familial hypercholesterolemia, riddled with heart disease. Where people basically are holding their breath saying, “My dad had his first heart attack at 29, I finally, I’ve lived beyond that.” Jill would have more information about how it is across other conditions. But certainly in the FH population even if it is bad news people would rather know because they’re empowered to act.

Michael: The FH Foundation is doing all this work you’re bringing attention to it and ideally more and more people get diagnosed and they start treatment for their children, for themselves, at younger and younger ages. If all goes well, if you do what you want to do and if this is all successful what happens with the disorder FH? And then also what is it a model for like what else can it help and form as we think about our health and other genetic disorders?

Katherine: The best case scenario is we turn the statistics on their head. As Jill said the estimates are that between 1% and 10% of people in the United States have received an accurate diagnosis. The foundation is working with EHR, records and labs and claims data. We put together a huge database of over 209 million Americans who are being treated for some type of cardiovascular disease or to prevent cardiovascular disease. And we built a machine learning algorithm to identify, to flag those individuals with probable FH.

It means reaching out to physicians since we can’t reach out directly to those patients. All of that information is de-identified although it has a unique identifier, but we can. We do have the information and we can go to healthcare providers who have high numbers of FH patients in their practice and try to educate them about familial hypercholesterolemia and see if in fact those patients do have FH. That’s one of the ways we hope to bring about accelerated change. Is it going to be easy? No, it’s taken us three years to get to this point.

I think it’s going to be a slug in our healthcare system that is so fragmented. But our hope and what we work towards every day is giving people the opportunity to know what’s at the heart of their heart disease. I mean literally finding people and getting them diagnosed. But as Jill said that involves bringing the healthcare community along. We know that research is not quickly bought and implemented into the real world healthcare settings and so we have to look at quality improvement initiatives within those healthcare settings perhaps to drive change.

Our goal is to hopefully get 90% of people diagnosed in the next two decades and dramatically bring down the rate of heart disease, or coronary heart disease in United States.

Jill: To augment what Katherine, the FH Foundation is being really influential in trying to reach out to the physicians to get them to have a better understanding of FH and why it’s important to identify and diagnose it. At the same time, and I think it’s really interesting to watch kind of the movement that’s happening in consumer-driven genomics. There’s now the ability for a healthcare consumer and nobody cares more about my health than me, right?,Somebody who is really motivated to stay healthy can actually get preventative health information from a number of qualified certified laboratories through kind of easy access models.

When you empower that healthcare consumer to have access to this preventative information, then they can find out that they’ve got FH and actually bring it back in and educate their doctor. In the reports that these companies can put out are all of the information and the practice guidelines that the physicians need to have right there. Once that awareness gets pushed kind of from the outside in and then Katherine and the FH Foundation are pushing from the inside out. I’m really optimistic that we can accelerate this process of getting the 90% of the people who have FH identified and on proper treatment plans.

Michael: Do you think that kind of model extends to other inherited disorders?

Jill: Absolutely. The laboratories that are driving these new changes and empowering the healthcare consumers to have access to preventative genetic testing. Then giving them the education and knowledge to take that back into the healthcare system. They’re doing it not just for FH but for other disorders, genetic disorders as well.

Michael: Thank you guys so much, this has been great and I hope everyone checks out the FH Foundation. How can people learn more about FH?

Katherine: You can go to thefhfoundation.org.

Michael: All right, Katherine Wilemon, Dr. Jill Hagenkord, thank you guys so much.