Dr. Elizabeth Ofili discusses the African American Heart Study with Dr. Thomas Nero. They also discuss her work at the NIH and the African American Heart Failure Trial and the role of community based pragmatic clinical trials.
Dr. Elizabeth Ofili discusses the African American Heart Study with Dr. Thomas Nero. They also discuss her work at the NIH and the African American Heart Failure Trial and the role of community based pragmatic clinical trials.
Good afternoon and welcome to Future Pulse. I'm Dr. Thomas Nero. Today we have the pleasure of talking with Dr. Elizabeth Ofili. Dr. Ofili is a nationally and internationally recognized cardiologist practicing at the Morehouse School of Medicine in Atlanta, Georgia. She has over 30 years experience studying and treating heart disease with a particular focus on cardiovascular disparities in the African American community, as well as in women's health.
Dr. Ophelia serves as the executive director of the Association of Black Cardiologists. She is the immediate, past board chair and the first female president of the Association of Black Cardiologists, during which time she led the initiative to implement the landmark African American heart failure trial.
Which was one of the, one of the really seminal trials when I was a young cardiologist . This trial, changed the practice guidelines for the treatment of heart failure in African Americans. In her capacity as founder and CEO of Health360, she leads the African American Heart Study, a groundbreaking nationwide observational trial studying lipoprotein A, which we're going to be discussing today. She has received too many awards or honors to list today because we would spend the entire hour going through those. And believe me, it is a bit overwhelming, but I have to say that I'm overwhelmed and pleased that we had the opportunity to talk to you today. Welcome.
Thank you so much, Dr. Nero.
I guess just to start off with, how does it feel to be so impressive? What you've been doing over the last 30 years, it's just, astounding. I remember hearing about you and , all of the, set up for the African American heart failure trial, years ago.
And, since then , one of the things I read, you've had an NIH grant continuously for the past 30 years. You've had something like 30 or 40 postdoc fellows that have come through your office. I'm just, I, I, how do you do it all?
Well, thank you so much. I really appreciate the opportunity to speak with you and your audience today. And I think really, as you know, because you obviously are doing very impressive work with the podcast, which I have listened to. I think all of this is really around the team that surround us and the people that have the passion and the commitment to do this kind of work.
So I have been very fortunate arriving in Morehouse, finding a group of individuals who were looking for a clinician to collaborate with. You know, when I finished at, um, Washington university and went on to St. Louis university for my echo, I did a lot of that research in that environment, but coming to Morehouse and Grady, It was really a different level of challenge in terms of who's getting sick, who's getting hospitalized, all much younger.
And that right away just fueled the commitment to try to do something. And with others around the table, especially basic translational scientists. It was really relatively easy to collaborate and just been fortunate that we have had the kinds of ideas that NIH is looking for and funded because a place like Morehouse School of Medicine attracts a lot of young people who are interested in addressing disparities in health equity.
So I will say it's just fortunate to be at the right place at the right time and be surrounded by people who have like minded commitment.
, it always brings up the idea that luck favors the prepared and clearly you were prepared for this. .
, so just to start off with today, we were discussing a lot about, disparities in the African American community as far as heart disease is concerned. And a lot of the, what we're going to talk about will be about coronary artery disease, , Lipid metabolism and lipoprotein level a but you really cut your teeth in the African American heart failure trial and I've always been wondering where the nidus for that trial came from because it really, , from my point of view is a little bit out of the blue and I was intrigued that it was so startlingly positive, for that community.
You know, you just asked such excellent questions. So thank you. To tell the truth that actually started with some of the earliest work that I did when I got to Morehouse
, they told me that, well, we've been trying to get a funding from NASA to study vascular changes in space. And I hadn't really done anything with NASA obviously before then, but. I told them, I said, well, I do have an interest in blood pressure regulation, salt sensitivity. And they said, yeah, we have a basic science project around that.
So that's sort of how we started to look at it and then came up with some hypothesis around nitric oxide and vascular function. And then it turns out that there is a correlation with individuals that have become hypertrophic or have LVH or left ventricle hypertrophy. with high blood pressure and nitric oxide deficiency underneath that.
So when the discussion around the African American heart study came up, I sort of pulled in some of that understanding and, you know, the basic science behind that did speak to nitric oxide deficiency that seemed to be more relevant in driving pathology of heart failure in blacks. So that's kind of how that came about.
And I guess the part of that question is why do you think it specifically? , positive in the African American community where it is less, , less positive in the non African American community. Do you think that there is a, a specific vascular issue or is this more of a question of social determinants of health
right. I think it's actually a mixture of both of those things because it turns out that nitric oxide deficiency has multiple factors or cofactors, some of which is also includes things like stress. and how the environment influences vascular function. The other thing is it's kind of not, it's not absolutely correct, although that's what's assumed in the broader scientific community, that it does not work in non African Americans.
Because if you look at individuals who are diabetic, Individuals who are older. Those individuals that data has shown also have nitric oxide deficiency. We do see better outcomes in that group. I think probably one of the main things that we don't talk about too much is the fact that because African Americans get, , heart failure or are afflicted with heart failure at a younger age, driven primarily by high blood pressure and some of the social determinants.
You are looking at individuals that don't have as much concomitant coronary artery disease because their age is not that advanced and yet early on they've picked up the blood pressure situation. So I think that magnifies the pathology in that group and that's what the data has shown in terms of nitric oxide deficiency. But when you have a compound that replenishes that, then it just significantly improves vasodilation, which we know vasodilation is important for everybody.
It's just for older individuals and even non African Americans, angiotensin may play a bigger role, whereas nitric oxide seems to play a bigger role with, uh, African Americans and black.
, I think that goes back to a lot of the stuff that we were studying years and years ago about hypertension and that, , various antihypertensive agents didn't seem to work in the African American community as, as strongly as we would have hoped for. And part of it was because we didn't study them, right, it goes back to sort of what the importance is of this trial that you're doing now and, and the African American heart failure trial is that, , you're studying the community that need, that we need to find out specifically in them, how that's going to be different.
And that's actually one of the things I wanted to go into today, , is, do you think that there really is a little bit of a difference in, , the vascular biology of African Americans?
I think part of what we constantly deal with, and that came out really loud and clear with the African American heart failure study is race is a social construct. And why are you doing this when you actually, you know, it doesn't matter if people are black or white, they have heart failure, they need to be treated.
I, you know, I mean, when you're young and you're going after something, you sort of go, well, let's do it this way. At that time, the thinking was that's who's affected with the disparity. They come, I can tell you the congressional black caucus. You know, I was, that was my first. A few days as president of the Association of Black Cardiologists, I was the first woman and I was thinking, oh my God, don't mess this up.
Um, you know, and then, uh, they came and said, well, what is this we hear? You know, at that time there was a lot of conversation around why are we using ACE inhibitors? It doesn't work in Black, beta blockers don't work. The clinical trials are coming up not too good. Why are you not doing something about this ABC?
And yes, by the way, somebody came and said, this drug seems to work on early studies from the VA. Why is the association of black cardiologists not getting behind it? And I said, you know what, we will get behind it. We'll gather people who have the scientific stature. And make sure the study is well designed.
And that's what we did. But later on, when the results came out so positively and FDA said, we're just going to approve it for African Americans. And I just said, you know what? It doesn't make any sense. Approve it for everybody. Now, that's all water under the bridge. I know, but there are some lessons that we need to take forward here.
That is, sometimes you have to study a group that have some maybe separate manifestation of a disease, heightened manifestation to learn more, not to isolate the therapy to that group, but to understand that there's a continuum of treatment and treatment efficacy. In this case, when we begin to look at how beneficial that study was, I think, as I said earlier, it's important to know it filled a critical gap at a time when ACE inhibitors weren't working.
We didn't really have a good compound that could contribute nitric oxide the way that combination of isosorbide hydralazine did. But now we know more, there's been new drugs doing some of that type of work. And I think The tragedy is these patient populations are still not getting access to that therapy.
And so whatever we talk about today, Tom, I really want us to focus our attention on it's one thing to study the drug and get it approved. It's another thing to get, make sure the population that's affected has access to it. Right?
, absolutely , the fact that we can't get the drugs that like what you're specifically talking about is the ARNIs and their use in heart failure, but secondarily also things like SGLT2 inhibitors also are very difficult to get, or get them approved, .
, if you, we can have these drugs, but if you can't use them, then it's not doing anyone any good. Uh, and, and your comments about, , looking at those, special population which has a heightened, , prevalence of disease, you know, we certainly do that in lipid, uh, in lipid studies all the time, right?
We start with looking at patients with, um, familial hyperlipidemia. And, , when we see FH patients, we start looking at them, we find out what the problem is with FH patients, the PCSK9 inhibitors story is just wonderful in the fact that it was the first drug that was started by genetic testing, right?
We tested, we found out what the cause was for patients who had FH, and then we found out what the problem was. We found out what the patients who had , under expression of PCSK9, right? They didn't develop heart disease, then it went forward. And so that, and that's really completely changed the way that we're going to be doing lipid management in the future.
, the idea that you can study this population and then not, uh, try to work from there in order to extrapolate out is a little bit, um, short sighted
Exactly. I 100 percent agree.
, so we're talking a little bit more about lipid metabolism and, , African American patients. , it's interesting to me , that when you look at African American patients, they are different, right?
We see a lot of different things as far as their lipid metabolism. They have a lower HDL cholesterols, for example, they have higher triglyceride levels. Uh, certainly there is, uh, higher rates of diabetes and we can go into. Why you think that is,
And then what we're gonna be talking about a little bit in a little bit is the elevation of lipoprotein little a that they do have higher levels of LP little a. And yet we don't have as much information on this subpopulation as we do on general populations. .
, I think that just understanding that, first of all, there's some aspects of, as you mentioned, the familiar hypercholesterolemia. Some aspects of personalized approaches to medicine because we're all coming to the table with whatever our genetic risks are, but also what the environmental risks are.
And one of the things that we learned early on is because for a whole host of reasons, and there's enough data now to show whether it's childhood stressors, trauma, aspects of isolation. Um, what happens when people are in certain households and they do not have the social support they need. All of those drive risk and then the environment that people are growing up in.
At the end of the day, when you feed this into a typical African American, , patient community where you have had these degrees of systemic, inequities, if not even sometimes frank outright racism, depending on how people have been, , engaged. One of the things we've learned early is. People have a much higher rates of high blood pressure, and that is not trivial because when people have those blood pressure, issues early on, like when I came to Georgia was when I saw people in their 30s and 40s with hypertension, you know, we were taught in cardiology and medical school that you kind of worry about hypertension when people are in their 50s, 60s and 70s.
I saw the opposite. Now, what does that do? Well, that actually fundamentally changes the vasculature. And then that in turn leads to aspects of insulin resistance, which then, of course, as we know, there's that constellation of obesity, , glucose insufficiency, hypertension, that for the longest time we called, , cardiometabolic risk.
And on top of that, even though the lipids are not what people would call very dangerous, HDL is a little bit higher, triglycerides not as high, LDL high, but not always the highest levels. All of these amounts put together on the backdrop of a, vasculature that has seen high blood pressure over a long period of time actually is toxic in terms of how that affects Target organ damage.
As we know, there's hypertrophy that develops and then, of course, subsequently what's happening with risk for myocardial infarction and heart failure. So I think overall, we have not really truly understood all that we could understand about why African Americans continue to have this high level of risk other than this issue with underlying hypertension.
And yes, diabetes . Because there are some, , environmental and genetic predispositions. So I think it's a combination of multi risk factors, it's not just one, but several. And then on the back, , ground of some of these other social determinants of health, which, which are just tremendous in terms of their contribution to risk.
, there's so many pieces here and sometimes it gets confusing for us all to be able to try to, eliminate all of the noise. And I wouldn't, I hate to call it noise because it's not noise, , to start focusing on just one piece of it because there are so many pieces here.
And I hope to get into that a bit in a, in a few minutes. On the end of the discussion about how we're going to, um, enact this information because you know what we're doing right now is a registry and that registry I'm hoping, and actually just to dive forward just a little bit is that I'm hoping that that registry also is going to be getting more information beyond just what the lipoprotein little a levels are and what the outcomes are.
So, , with that trial, let's, let's dive into your African American heart study a little bit. Uh, why don't you tell us how it's structured and what the, , primary goals are going to be? Well,
so the African American Heart Study is actually sponsored by Amgen. And Amgen came to us, um, about a year and a half or two ago saying that, we know that Lp little a. Is more problematic in African Americans. His levels are higher period and the question that we don't what we don't know is what is the consequence of this?
Is it the same as what we see in whites? What has been reported, for example, with the U. K. Biobank that you alluded to earlier? Or is there a worse outcome? , I was asked to serve as global PI of the study, which I was just, you know, really, really honored to, to do and came back with a study, , design that was essentially a case control.
And the reason for the case control is It allows us to understand, first of all, you know, you start from base, a cross sectional, everybody who comes in, either they've had a heart attack , or a peripheral artery disease, or they've had a PCI intervention, or their controls, which means they haven't had any of this.
And then we kind of work forwards. To say, based on their baseline levels of lipoprotein A, and it's again, it's measured differently, as you know, through a molar concentration, which the data suggests that that is a more specific way to analyze it versus just looking at the mass. But knowing that we're getting better accurate measurement, what does this correlate with in terms of number one, did it correlate with higher levels at baseline?
Did it correlate with additional biomarkers related to inflammation? And, or did it correlate with some genetic predisposition? So there's going to be some genetic assays, et cetera. So this is more or less a cross sectional, but also going forward. Cause you know, we follow people three years out just tracking events.
And that's again, going to say, number one, do African American patients that have varying levels of it. And again, we can look at tertiles and quartiles of it, what happens to people. Three years out every year looking at, are they more likely to have events, uh, ischemic events and so on. So I like that sort of observational structure, but I'm also pleased to say to my patients as we're getting them enrolled that we're doing this number one because we want to understand more.
But we also know from the data we have right now that this, this compound is not good. It does terrible things to your risk of stroke, heart attacks, et cetera. So at some point, the fact that we now have some drugs that we're looking at is something we all need to keep in mind.
So they're all levels of these that makes this really a very exciting study.
, the issue with the LPA, as you were discussing with the, um, molar concentrations that you really had to look at an nanamols per liter instead of the milligrams per deciliter that was commonly being used before the idea that this this cholesterol molecule.
Um, is not cleared by the same mechanisms as LDL is cleared. And with that, you'll have more of these molecules there that are then going to be interacting with the cell wall or the vessel wall. And in addition, it mimics plasminogen so that it blocks the effect of plasminogen. So it's more like rhombus, you know, all these things, uh, you know, they, they, They add up.
I mean, it's a, it's a, it's a bad actor. Um, I will be very intrigued to see what happens with, both the horizon and Oceana trial.
, my view is, There's so much that needs to be done and we can do, enroll everybody you have in Oceania. And then with the African American heart study there's gonna be PE there. There will be those individuals that obviously will also be fit to participate. And I know you mentioned about the registry, if it's going to be just LP little A, so, so the registry was actually separately approved and funded through a small business innovation research award from NIH.
And that is. Just based on the Health360x platform that engages with, um, patients, helps them self monitor, manage their health, they have coaches. So that was the framework. So the registry currently includes over 3000 patients and they're not actually all, , we actually have not started to put in the African American heart study patients in the registry.
That's going to come later as we get all acclimated with the respective EMRs. But the most what we think is the innovation around the registry is that we are tracking social determinants of health. So we're using the FedEx toolkit because it's a way, you get all the, um, standardized measures.
And by bringing that in, regardless of the disease area, which all cardiovascular diseases is, um, eligible to be a part of it, it would allow us down the road, once we get lots and lots and lots of data into it, to look at things like predictive modeling about who's going to have events based on what they have.
So it's going to be a sort of a different kind of registry at the practice level. But that adds these layers of understanding to help with decision support at the bedside. So we, we are quite ambitious about that,
And, and, and, and, and you should be, , the idea that , , you're getting , multiple things out of this trial, which is always important that we just don't look at the top line results and that we actually use these structures in order to build upon for , later research. One of the things you had mentioned in passing was that you're also looking at inflammation within this population as well. Can you speak to that just a little bit?
I think part of it is in looking at the how Lp little a leads to pathology. Inflammation is in the mix of that and obviously, , thrombotic, episodes related to the inflammation as well as the plasminogen, , effect. So we actually, through the study itself is measuring various inflammatory markers.
As biomarkers, so again, how much of that will, will pan out? I think we will have to wait and see, , but the basic science data does suggest that part of the pathology behind lipoprotein A is actually driving inflammation.
, it's going to be important but if people have inflammation, it, the blood vessels, it'll affect lots of organs. And that's what I like about trying to understand that underlying pathology and potential therapeutic targets.
And, and that's one of the problems, as you alluded to earlier, is that We can have these, we can have ways of treating these therapeutic targets, but if we can't get them to the patients, then it's not going to do them any good. the problems with these drugs now are that, each of these drugs that are coming out are going to probably cost somewhere between six and ten thousand dollars a year, right?
But, , one of the things that you've done with this trial that I think is so, exciting is that you're creating a base, , a platform for, , pragmatic clinical trials.
And I think that is really going to be, it has to be part of the future of medicine. It may, it's not going to be the future of medicine, but it has to be part of it. Right. Um, certainly when we look at pragmatic trials and, and they are not blinded, there's going to be bias into while the patients are treated.
. We have to be able to start looking at it, to be able to form the questions. , so that we can get those answers and if, , you don't mind talk a little bit about your approach to pragmatic clinical trials
. Yeah, I think that, um, so I've done clinical trials for a long time, and one of the challenges, in addition to the fact that. We don't, you know, sometimes the patients that are at the highest risk are not participating for a number of reasons. It's also the fact that the way the studies are designed, that narrow focus.
Once the study is approved, there's generally not a human being that fits that narrow focus. So, you're like saying, okay, yeah, we got this fantastic drug, oh, by the way, we had to sanitize and make sure everything was perfect, and that's how , we treated people. So, the question that we then asked was, What about just going and, and again, this came out of a National Academy of Medicine, discussion, which, , Rob Califf, who's now, , FDA commissioner, was very much in the middle of that and a lot of other people just asking the question, how can we get the broader, uh, community participating because we are watching all these trials go overseas, even NIH is sending studies overseas, and we've got people here who, whatever you think, They do have some things around them that would affect how they metabolize drugs, whether it's BMI or the air we breathe or the kinds of food we eat or the lack of activity.
We need to study these regular people. So we proposed to NIH, what's called a decentralized clinical trials, , which means we're kind of going where. The patients are, we're not necessarily going to be at top academic institutions. We're going to go to doctors who take care of these patients. So we're that small community health centers, a small doctor's offices, but then came, how do you manage the infrastructure to address that, which is how we came up with this.
Real world, um, being able to access the EMR to then get an understanding of, uh, maybe buying in some efficiencies, maybe recruit people more efficiently, but importantly, follow people out without having to spend lots and lots of money adjudicating. And so that is that pragmatic thing that we're hoping means less cost.
And hopefully that would eventually translate to not inaccurate data. But more data that we just have an opportunity to work with differently. I know we all are concerned about AI and machine learning, deep learning, et cetera, and there's reason to be concerned.
But at the end of the day, all of that data that's coming out of electronic medical records needs to be harnessed so we can have some learnings and translate that into research. So it's not every time. The company X wants to do a drug trial. You have to go from the very beginning to start pulling up.
Well, you have all that data that's residing in people's records.
Are you going to be able to, , extend this followup on these patients? Because it seems like that would be a natural for, uh, the way that you're doing this trial because you, you know, it doesn't essentially, it doesn't cost you anything, right? It's already, all the data is there. It's coming in. Um.
Yeah. And you just keep on, keep on watching them over, over
Yeah. What I have learned and you just asking these excellent questions is I've learned to leverage. So for example, pharma has an interest in getting this knowledge in this gap addressed, but also knowledge about drug discovery. Well, NIH also has interest in knowledge about early drug discovery, so NIH wants to know about these kinds of registries, which is why I think they funded us.
So, this is how you're going to get longitudinal with the registry. using real world data. And I definitely think the value of the registry, you know, starting now, you know, we were so glad when the ACC brought us in as a late breaking trial, but that just told us about how there's an interest in this area.
But to me, as you alluded, the value really is as when you get into millions of Of individuals in there that have been followed for 10, 15, 20 years, that's where the value begins to truly accrue. But of course, it starts now.
So one question I have on the, , database that you're building up now is you're going to have some blood samples. And so did you also plan into the trial so that you could then retest those samples that are going to, are you going to bank some of that so that, that future questions could be answered?
So this is a very good question, but we are what my team calls, , crawl, walk, run. So we are very much in the crawl stage, right? To get blood samples in this patient population is not easy. And even though the registry, informed consent says we will, if we need to get blood, we're not yet collecting blood.
And the main reason behind that is kind of have to get our infrastructure right before we start storing blood. And probably that's going to be in partnership with another, um, Organization that does this very well. For example, the ALL OF US.
The ALL OF US, studied looking at a million people biobanking with Mayo. So we need to kind of understand those lessons and then see which aspects of even maybe not. Fresh blood, but blood that's already being done for other things. How can that be repurposed? So that piece about the biospecimens we're currently not running, and it, but potentially a missed opportunity, but we more view that as getting there as we continue to build the infrastructure.
Yeah, you've bitten off a fairly big bite of that apple already. So, um, to make a bigger bite might, might not necessarily always work. , one of the other questions that I had, , you've been so successful. And one of the things that we were trying to figure out was how to improve our outreach to the African American community locally.
It's not as easy as people think. You can't just say, Hey, we're interested in you. Come, come here. You have to go out to them and in a way offer them something that's important to them so that they can understand because, there's a, a great deal of, misunderstanding and, , concern over the, over history, and research in the African American community, , how would you, tell someone like Ayanna and my fellows?
If they're going to reach out into the community, how you would do that, what would you do? , what are the steps?
Yeah. , I a hundred percent agree. I think it's recognizing that this is not top of mind necessarily. People always think it's all about Tuskegee. Yes. Tuskegee has a role to play, but then there's the Henrietta Lacks. So people are asking questions. What are you going to do with that data?
What are you going to do with my information? So just being upfront involving them in some of the discussions and decision in our case. We actually involve them in aspects of data through their doctor's offices. Helps people know that they have skin in the game. The other piece is just valuing people's time, right?
So if somebody comes in and says, you know what? Yeah, I want to learn about this. We shouldn't assume that everybody who's quote unquote in the community does not have capacity to understand. They're actually people in the community who know a lot more about some diseases than many of us as doctors, because they've lived those diseases.
I think people want to be respected for what they know. So I know Iyana probably knows this going out into the community and, talking to patients. The first thing they want to know is who are you? Where do you come from? What's your motivation? Why are you coming to knock on my door? Why should I do this?
And the why should I do this part is really the most gratifying part is African American patients. will participate in studies, not because of themselves and what they have, but because of how it will help their family members, their community members. But being honest with them, we don't have a not enough knowledge. And when I say to people, guess what? We take aspirin. Did you know there wasn't enough black people studied with the aspirin studies ago? Yeah. So we need to be a part of it in order for us to know that it's going to work in us and they get that.
If the research doesn't reflect my patients, then I can't extrapolate the information from the research to treat my patients. And that, , regardless of where they come from, , they need to be represented.
And, , hopefully that, information gets out to them because, we need them, we need everybody, , not just, not any one population, we need them all. Well, Dr. Ophelia, I just have to thank you so much for taking the time today to discuss these trials. The African American Heart Study, I think is going to be a wonderful, uh, registry and trials and series of trials that are going to grow from this. It is going to be the foundation for a lot of what we do with the African American community.
I think that giving back to the community as you have, um, is just, it's worth its weight in gold. , do you have any last, uh, words of wisdom before us before we close out today?
Well, I think I just want to say thank you to you, Tom, , for the work that you're doing, , the team that you have, Iyana and, Josh and, , this work matters , , the task is huge and it can sometimes be so daunting and intimidating, but what we're learning is with everything we do and learn from our patients benefit and so it's just Recognizing is you and I know that cardiovascular disease is such a sudden killer and whatever we do to learn more and understand and ensure that those learnings translate to the community so they can take advantage of it.
That is just fantastic. And I just want to thank you for the opportunity to come and share some of my thoughts in this area.
Well, thank you again. And I'm sure that we'll be back in touch as we get more information from the trials. Thank you.