The Latest on the Landmark Miami Heart Study

Seven years ago, a team at Baptist Health's  Miami Cardiac & Vascular Institute (MCVI) launched the Miami Heart Study (MiHeart). The researchers are following 2,549 volunteers between ages 40-65 who had no symptoms of heart disease at the beginning of the study in order to track the primary factors involved in the development of coronary artery disease. 

Find out what makes the data from this study so valuable to researchers around the world in this discussion with host, Jonathan Fialkow, M.D., deputy medical director of MCVI, who is the senior author of the study, and Khurran Nasir, M.D., chief of Cardiovascular Prevention and Wellness Division of Houston Methodist Hospital, who is MiHeart's principal investigator. 

Transcript

Announcer:
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Dr. Fialkow:
Welcome, Baptist Health Talk podcast listeners. I'm your host, Dr. Jonathan Fialkow. I'm a preventative cardiologist and I'm the chief population health officer at Baptist Health South Florida, the deputy medical director of Miami Cardiac & Vascular Institute and chief of cardiology at Baptist Hospital. Cardiovascular disease remains the leading cause of death and disability in the United States and other modern countries. And after years of decline, the rates of cardiovascular deaths have been increasing in the US over the past few years. Some of this may be attributed to an aging population, a more overweight and sedentary population and a more stressed and sleep deprived population. Yet with all the information we've gained regarding our cardiovascular system over the past decades, we are still unable to define the true risk in an individual. From a large population standpoint, we know that smoking, hypertension, lipid and cholesterol abnormalities, diabetes, genetics and other factors can contribute, but not every smoker will have a heart attack and not every presumably healthy runner is immune from a heart attack.

Dr. Fialkow:
We have with us today, a national and international leader in cardiac prevention with particular focus on the information we can glean from imaging, biomarkers or blood tests and other parameters, most intriguingly genomic testing, to better help us determine what truly leads the cardiac disease and perhaps more importantly, in whom we may better predict a heart attack or other outcomes so we can act to prevent that event. Dr. Khurram Nasir is the chief of cardiovascular prevention and wellness at Houston Methodist. Dr. Nasir is the principal investigator in the Miami Heart Study, which created a database that is unlike any other in the world that is now gaining recognition and broad interest by leading academic centers and in industry. It's a great pleasure and an honor to have Dr. Nasir with us on our podcast today. Welcome, Khurram.

Dr. Nasir:
John, such a pleasure to be with you and especially having a conversation around topics which are near and dear to MCVI and at Baptist Health, so great to be on board today.

Dr. Fialkow:
Well, we certainly recognize your great expertise in being a real catalyst for a lot of the work that's been done at MCVI and in coordination with where you are at Houston Methodist. And let's get into that a little bit. So before we get into the Miami Heart Study and its unique aspects, let's talk a little bit about setting a baseline for what we're discussing. So talk a little bit about atherosclerosis. We know there's a hardening of the arteries, as a waste basket term we know it's inflammation, but what don't we know about atherosclerosis has driven this further investigation that led to the Miami Heart Study?

Dr. Nasir:
John, I think you laid a great foundation in talking about risk factors within the whole spectrum of coronary heart disease is something that's new to us. Almost less than 100 years ago, we had no clue about coronary artery disease and suddenly we started realizing young men coming from World War II having certain heart attacks and strokes and dying from it. And, of course, Framingham Heart Study then cascaded and gave us the first risk factors. Atherosclerosis means development of the plaque build up in the arteries. And of course our understanding about it, it's pretty new, especially among individuals who have not yet had any heart disease or invasive procedures. It wasn't until 1990 that Arthur Agatson, one of our own also from Miami, showed us that using a CT scan you can pick up calcified portions of the plaque.

Dr. Nasir:
And over the last two decades, we clearly got to learn that this is the main substrate all the main risk factors for cardiovascular disease, especially heart disease. However, at the same time, we don't know what is truly causing these plaque to build up to progress, what are the biological determinants. So think about it, so far we have truly scratched the surface. And the reason for that is we just didn't have good tools to do that. However, with the advancement in the multi-detector CT technology now where you can give contrast and even within one heartbeat assess the entire architecture of the coronary artery disease I think so we are at a very exciting time where we have started learning a little bit more about atherosclerosis, the number one cause of heart disease.

Dr. Fialkow:
You actually started that wonderful introductory explanation with a comment and I think I want to put that context. Someone has a heart attack, someone has a stroke, of course, we're going to be very aggressive to intervene to decrease the chances of that second event. But we're talking about people who would have no overt evidence of having vascular disease. We know you don't go to sleep with a normal artery and wake up with a blockage the next day, so there's a process. So we're talking about an earlier detection of who may have atherosclerosis and then of course finding which of those people with atherosclerosis may go on to have more aggressive, a bad outcome, so to speak.

Dr. Fialkow:
So as you bring that, what are, if you will, and you alluded a little bit, before we get to Miami Heart Study, you're talking about imaging, testing, quick scans, safe scans that can give us this plaque assessment and plaque composition. So talk about who right now in our current standards of care, where does that come into play? Where do we get these these tests looking at calcium score? And what's the difference between the calcium score test and the CTA, for example?

Dr. Nasir:
Just to start on this, John, the current models that are used to really identify individuals who are at risk are still risk based, which were first defined almost 60 years back. And what we have been doing over the last few many decades that we take those risk factors, put them in a model, shake it up and come up with your risk of having a heart attack. Now, that's been the standard or, I would say, the foundation in how you decide someone in the current practices whether you may be more aggressive with... Of course, everyone needs lifestyle intervention, but whether you would need lifesaving therapies like statins that lowers the cholesterol or aspirin.

Dr. Nasir:
However, what we have learned over the last 20 years that these risk prediction models are extremely limited. And for the last decade, a lot of work from Multi-Ethnic Study of Atherosclerosis and from our group have clearly shown that these methods are imprecise. Among individuals who may be coming in your clinic, where you will say, "Well, you are high risk and you need to commit to a cholesterol therapy for the next 10, 15, lifelong," almost half of them, when you use the simple non-contrasting T scan, that shows that if you don't have any plaque buildup and it's now commonly known as the power of zero, they are at a much lower risk of having a risk factors.

Dr. Nasir:
Now, of course, you also mentioned that just because your cholesterol's high doesn't mean that all of them will have atherosclerosis and vice versa. And this what we are seeing, a huge diversity Where almost one third of individuals who may have no risk factors actually have tremendous amount of disease and at a higher risk who need to be treated aggressively. And vice versa where almost half of individuals with worse cholesterol may not have any plaque where you can be flexible with them with just lifestyle, I would say, intervention. So clearly we need to do a better job in identifying the risk of the person who's sitting in front of us, and in that regard, the calcium score, and hopefully the CT angiogram, which is giving a contrast, and we can talk a little bit more about it, would truly help us in making those decisions.

Dr. Fialkow:
So, as we said, the general risk factors that have identified over decades are appropriate for populations. If I have 10,000 60 year old smoking men, we'll probably see more heart attacks over 15 years than 10,000 non-smoking 60 year old men. But to the individual, we don't know what the risk necessarily is. And now we're getting into more precise or precision approach. And was that the intent of the Miami Heart Study? Talk a little bit about what your thoughts were and what the leadership's thoughts were in putting together that database. And then of course we'll get into what exactly is in that database that's so unique.

Dr. Nasir:
Again, John, you have to go back to 2013 and 14, by that time what were our challenges? Our challenges were very clearly that the risk factors prediction were imprecise, and we truly didn't have a good understanding of not only the individual risk, but what is causing the atherosclerosis or the plaque buildup in the coronaries. And the good part is newer challenges bring newer opportunities and a kudos to, I would say, the leadership at Miami Cardiovascular Institute and a lot of folks within, I would say, the Baptist in ecosystem, that we all came together and say, "Rather than..." I clearly remember Mr. Kiley's remark that we can wait for other to give us the information and follow or we can lead. And the decision was we wanted to lead. And the intent was to rekindle the spirit of the Framingham Heart Study that was done in 1948, in trying to understand what causes heart disease, and now it was trying to understand what causes atherosclerosis.

Dr. Nasir:
It was a challenging project. When we reached out to NIH, they told that it is very ambitious, can't be done. However, that's not the spirit at Baptist Heart. And we put a team together. And in three years we recruited, with the help of our community who truly wanted to contribute to this new knowledge, not only for themselves, their community, but for the rest of the world, where eventually now we are at a stage with our internal, I would say, national and international collaboration. We can unravel the secrets of what causes the number one cause of heart disease that is atherosclerosis.

Dr. Fialkow:
So the Miami Heart Study was... Tell us, first place they were asymptomatic patients. I think it should be very clear that we're talking about people in the community, middle aged people, with no evidence of vascular disease otherwise. And by entering into the study, what was done to them? What was the data that we collected at the time?

Dr. Nasir:
So think about it, it was very much based, John, on the traditional cohorts, for example, the famous Framingham heart Study and the Multi-Ethnic Study of Atherosclerosis, which recruited almost 6,000 individuals all across US, but guiding us what the non-contrast CT, the calcium school. So, what was unique about Miami Heart Study, first of all, this was all, not exclusively, but a significant proportion of the Hispanic, Latino community. There are no large studies specifically in this regard, number one. Number two, as you know, which you pointed out early on in your introduction that now we are seeing a resurgence of coronary heart disease in the young, most of the prior cohorts were in elderly population. This was a young middle age, age 40 to 60, so that was the second thing. But the most unique piece of the Miami Heart Study was this is the only cohort in United States, a population based cohort, where for the first time we were able to employ the novel CT scans that in one heartbeat can give you all the information of not only the plaque, the types of plaques and much more beyond.

Dr. Fialkow:
So actually Khurram, let me interrupt for a second because I think that's very key. So the patient, the subjects were healthy people in the community. They said they're entering the trial and were saying, "Let's look at a bunch of stuff so we can then see what correlates in the findings with what may go on down the road." So they all got a CT angiogram, which is a very safe, fast, scan, as you articulated. And we're looking not just for blockages, but we're looking at presence of atherosclerosis and what is in that plaque that might differentiate the individual on their outcomes. Is that an appropriate way to explain that?

Dr. Nasir:
Yeah. And John, one of the key things is that we have slowly started learning that even if you have plaque, not all plaque are the same because the plaque has a life of their own. And as a part of the process or a healing process, some of the plaques may actually be extremely stable. That would suggest that the risk for those individuals having a heart attack, at least in the short period may be lower. Whereas, now we have been learning from individuals having heart attacks like acute coronary syndrome that there are some plaque features that put individuals at more risk.

Dr. Nasir:
And then again, there is no other modality that can give us that information non-invasively and in a safe manner. And think about it, atherosclerosis being the underlying pinning foundation of heart disease, yet in 2022 there is no other cohort in the country that can provide us that information. I hope that what we have been able to do at MCVI and Baptist Health will spur interest, not only with all the other genetics, precision medicine, social scientists, all of us coming together, but also incentivize NHLBI to invest in further studies like this.

Dr. Fialkow:
2,400 individuals, asymptomatic middle-aged people, have among their tests a CTA. As you said, we're looking at not just having we think I have a blockage, I'm going to have a heart attack, not necessarily, it could be stable, at least like you said, shorter to medium term and people without significant blockages might have other kinds of composition of the plaque that might put them at risk, which is what this database is looking for to further determine. Talk about the genomics for a second though, because that's another aspect. We have the imaging component, which is part and parcel of what the Miami Heart Study developed. That database is unique. There's a lot of interest in that. What was the thoughts in creating sampling for genomic testing? Where does that stand as part of the heart study evolution?

Dr. Nasir:
John, as we've started learning for many last two decades that genetics seems to play an important, if not the most important, role in development of heart disease. Now, the questions from our standpoint, the genetics was very important from few standpoint. Number one, as you pointed out, we have started noticing a lot of two diverse groups. One was individuals who without risk factors, runners leading a healthy lifestyle and having early plaque and a lot of plaque. And on the other hand, diabetics with severely elevated cholesterol, having no disease. So this is now translated into this concept of vulnerability at one end, where you are vulnerable in spite of the fact traditionally you shouldn't get the disease. And then among people who you would think that they are walking with underlying disease, but actually have not. So we truly think that there is a tremendous opportunity for us to learn from the genetics, whether there is a genetic up regulation, down regulation and influence of on the proteins or the biomarkers that can give us insight what's the shield that these individuals are holding.

Dr. Nasir:
Because, think about the value of this, currently our approach in managing heart disease or atherosclerosis is taking away the risk, for example, lowering your cholesterol control in your blood pressure and other. But what about if genetics can guide us and tell us what is the variation in the genetics or the molecular basis that is providing shield to those individuals that can eventually be translated into therapeutics? So not only we are taking away the risk factors, but also providing the shield in future to these vulnerable individuals.

Dr. Fialkow:
And is that really where you see the development and the goal of what we call precision medicine? I think that's really the holy grail. It's not what could happen to me relative to what happened to others, but what really could happen to me or what do I have to do or what medicine is best for me. I think when we as practitioners we do get that pushback from people quite often when we prescribe what is recommended based on guidelines in clinical trials, and they may say, "Well, do I really need this?" And, and of course the answer is maybe, it's probabilities, the data in big group says it. But is that what your particular vision is for what we'll have with precision medicine and the cardiovascular prevention? Elaborate on that a little bit.

Dr. Nasir:
John, it's the approach taken by many of the physicians in your group, and I've learned it from you too, it's all about the right patient, right time and right intervention. So, of course, on an average we truly think that those patients may benefit. But the question is how can we reduce the noise? That's really what it is, heterogeneity, because not all diabetics are the same and you and I clearly we have seen that all you need is three diabetics and one will have no plaque and one will mild and one with severe, but if we treat all of them the same, then of course we may be over treating some and under treating some. And in 2022 it's not only about statin decisions. As you know, aspirin is a hard choice right now in primary prevention, so unless and until you have a lot of plaque, you may not be a good candidate.

Dr. Nasir:
And with new interventions coming in, such as ICO Sapien, the purified fish oil and some of the cardio metabolic therapies for diabetes, I think the heart scans, the calcium testing, and hopefully the CT angiogram in some of the, I would say, select populations can help you truly guide who are the individuals who need it. Not only at an individual level, John, of course, in your wearing the hat of the population health management and how do you allocate the resources? So now you can say, "Well, a subset of the population, the system, or the societal resources can be flexible. Where do you on to invest more among the highest risk because that's where you will get your dividends?" So we truly believe, and cost effective analysis have shown that upstream investment in these technologies, in identifying the right patient also are cost effective from the health system and the societal basis, not only informing the patient in front of you.

Dr. Fialkow:
Well said. How do you take these population data, apply them to an individual? How do you take limited resources, which we have in healthcare, and apply them where they're best used? And that's the exciting part of where we're going. I do see down the road, and you can tell what you think, that people will have, maybe based on a blood test profile, maybe based on a calcium score or CTA, quite frankly, which again, given the advancements of the technology becomes rapid and safe and hopefully inexpensive and they'll have a profile. And this is your prescription for exercise. This is your prescription for sleep. And this is your prescription for food variability. I won't say diet, I don't like using that word. And medications were appropriate. And I think thanks to you and your vision and your leadership, that is where this data is supporting and where it's driving us.

Dr. Fialkow:
Is that where you see things going? Is that where you eventually see ultimately a goal for us as providers in having to deal with someone in front of you who's asking questions as well as broader populations of people?

Dr. Nasir:
Thank you, John, for mentioning this. Honestly, I think so. As you and I, we have discussed multiple times, we're still in the state of disease care. And hopefully in the spirit of trying to promote healthcare, this is truly a mechanism. I'm not saying that calcium testing or a CD is going to be the whole answer. It's going to be more information from different inputs that may include variables, your lifestyle, your food habits, your exercise prescription, but the most important foundation truly to understand, especially in 2022 and moving beyond, do you need treatment with the vast majority of options that we have? As far as where we stand right now, there is no better test than trying to understand what's your plaque burden, but is that all and all? No, I don't believe. I think so you can supplement who may need specific therapies, especially from the diet, physical sleep, and of course, as you know, with Dr. Walia we are working a lot in trying to understand the relationship of sleep and atherosclerosis.

Dr. Fialkow:
A frequent podcast guest.

Dr. Nasir:
Yes. And there are so many things, but I think so we are laying here the foundation. And I just wanted to point that out, John, that it truly takes a village to get there. Looking back seven years back I think that without the significant contribution of MCVI and the innovative spirit of Baptist Health, and more importantly, the leaders that I truly want to acknowledge here, without their support, none of this would have happened, such as Jack Zifer, Barry [inaudible 00:21:24] and yourself, Bob Bolenger and Calvin Balbock from the community. I think so it was a village and that whole spirit of what the community in Framingham came together to answer not only for themself, for the word, I think. So that was what it took us to build this. And now truly we are open to investigators and with open arms we are inviting folks, experts from all across the country and internationally who are heading to our call. And as you have seen, significant collaboration efforts have led into the last many months.

Dr. Fialkow:
So let's finish with that point, which again is, as always, very articulate and well said. So the Miami Heart Study database, 2,400 asymptomatic people at the time of entry, it's about 50% women. What's the male to female ratio?

Dr. Nasir:
So it's interesting, it's almost one is to one, maybe about 50% each are men and women, age 40 to 60 mean age is around 50, but we still have about 25% individuals less than 45.

Dr. Fialkow:
So again, very unusual to have such a high representation of women in the study. Imaging study down to plaque composition levels, various other parameters of vasomotor activities, biomarkers, blood testing, sleep surveys, great data. If someone, an academic or someone wanted to have access to that data for a potential or research study, what's the best way for them to contact you or us? What would be the way they would let us know that they're interested?

Dr. Nasir:
John, as you know, as we were designing the study, the idea was we wanted more hands on the table, more expertise. Of course, there's not everything that we can do ourselves. I'm not a genetic expert or a social expert and vice versa. So we are inviting all these expertise all across the nation. The best way is getting in touch with some of our primary instigators like yourself, myself, Dr. Feldman, and there is a website they can send us an email.

Dr. Nasir:
But the process usually work, if you have an idea you outreach to Miami Cardiovascular Institute, our investigators, there is a process which we will help and hold the hands in creating the proposal. There is a committee that reviews the proposal about its appropriateness, whether it can be done, whether there is an overlap with other proposals. And once it's approved, then we have our own teams locally, as well as at Houston Methodist. And of course with some data user agreement, the data can be shared. So truly a great opportunity for this multi-institutional collaborations. And I would definitely use this podcast to invite as many people who are interested in this unique data set.

Dr. Fialkow:
Well, thanks again, Khurram and we'll have a link in the program notes to how others may be able to communicate with us if they have any interest in taking part in database. This truly was visionary on your part and by the others, as you mentioned, and it's a true collaborative effort, and this database should be used to foster conversation, thought, innovation and the further learning of atherosclerosis and avoidance of cardiovascular disease and outcome. So again, thanks Khurram. This is, again, exciting, revolutionary approach to cardiovascular disease, finding those patients at risk. We hope to have you back soon for updates on the Miami Heart Study and maybe deeper dives into some of the concepts or components. Thanks again, Khurram.

Dr. Nasir:
Well, thank you, John. And again, I truly believe that the Miami Heart Study at Baptist Health South Florida and Miami Cardiovascular Institute would truly shine and lead the way be, the north star like the Framingham Heart Study that guided us what risk factors led to heart disease and now truly this study I think in the next five to 10 years will provide the foundation in understanding the subset of heart disease, atherosclerosis, its management treatment and prevention. So thank you so much for having me.

Dr. Fialkow:
To our listeners, as always, please send any thoughts, ideas or requests for future podcast topics to baptisthealthtalk@baptisthealth.net. That's baptisthealthtalk@baptisthealth.net. To our listeners, again, please stay safe.

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