Jan 5, 2021
This week's episode is special: To start 2021, Circulation's Digital Strategies Editor, Amit Khera, hosts a look back at Circulation's response to the Covid-19 pandemic. Circulation's Executive Editor James de Lemos and Senior Associate Editor Biykem Bozkurt discuss the initial days of Covid manuscript submissions to Circulation. Then Amit interviews author Fatima Rodriguez and her findings of racial and ethnic differences of patients suffering from Covid-19. Finally, Amit interviews authors Nicholas (Nick) Hendren and Justin Grodin as they discuss their article, which was one of the first science outputs from this AHA COVID registry.
TRANSCRIPT BELOW:
Dr. Amit Khera:
Well, welcome to Circulation on the Run. This is Amit Khera. I am digital strategies editor for Circulation, and I have the privilege of standing in for Carolyn Lam and Greg Hundley on this very special edition this week. We have no Circulation issue, so we get to use this and we thought we would use it for a really special look at COVID the Circulation response. It's a time to take a pause and reflect on what we've seen so far this year and what science and initiatives have come out of Circulation. And it's a real privilege today to be joined by first senior associate editor of Circulation, Biykem Bozkurt, who's professor of medicine at Baylor College of Medicine, and also James de Lemos. He's executive editor of Circulation and professor of medicine at UT Southwestern Medical Center. Welcome to you both.
Dr. James de Lemos:
Thank you.
Dr. Biykem Bozkurt:
Thank you, Amit.
Dr. Amit Khera:
Well, Biykem, I'm going to start with you. I remember when COVID came out, it was, we were all overwhelmed. The data were coming fast and furious. Most importantly as cardiovascular specialists we wanted to know how to manage these patients and what manifestations we're seeing. Things were coming from all over the world, and you were tasked with the challenge of, well, how do we organize and curate all this? And what can Circulation do to be most helpful in this response? And you came up with some really creative ideas that I really lodge you for. Maybe you can tell us a little bit about what was going through your mind when this was starting and what are some of the initiatives you started around that?
Dr. Biykem Bozkurt:
Thank you, Amit. And I really appreciate your pushing it to reflect. In early March it was clear that COVID was surging and we had to create a platform rapidly to disseminate the insights and the best practices from around the world in a timely fashion, and also inform future research for the fight against COVID. We discussed amongst the senior editors, and it was apparent early on that we would not have large-scale multicenter trials. And most of the information was going to come from site experiences and our cohorts, which were so valuable, and everybody was yearning for that information. With that framework in mind, we thought the best platform would be to do a call for submission of rapid research letters. And also we thought of interviews with experts from the hotspots, and we rapidly assembled a Circulation COVID editorial team, which comprised of me along with my colleagues, Salim Virani, Erin Michos, and then both of whom are the guest editors at Circulation, along with Mark Drazner, Darren McGuire and yourself.
Dr. Biykem Bozkurt:
And we created a call for rapid research letters for COVID and also started doing short video interviews from pandemic hotspots around the globe. We wanted these interviews to be dynamic, informative, conversational, both recognizing the crisis and the human factor as well as the best practices. We were so hungry for information. So we thought of a dyad approach where the interviews would be conducted by early career fellows in training, along with regional experts from the hotspots who were leading the fight formulating solutions. And we are so indebted to these experts and heroes for sharing their stories and experience on the cardiovascular presentations and the practices and how they were managing their patients. And these were called COVID updates from the front lines.
Dr. Biykem Bozkurt:
We had approximately 19 interviews with leaders from Seattle. That was one of the early hotspots. Then we moved on to Singapore because they were having such valuable and successful interventions. Then we went over to Madrid, Spain, where there was a huge hotspot, of course New York City. Then we interviewed with Milan, Italy, Brescia, Italy, Wuhan, China, New Orleans, South Korea, Salt Lake City, Paris, French, Houston, Texas, Atlanta, San Francisco, Delhi, India.
Dr. Biykem Bozkurt:
And we also try to address not only the local expert's approach to how to treat and manage and what they were seeing, but also strategically how the health disparities were being handled, how the emergency room or ICU clinicians were tackling COVID. We also try to provide a nursing perspective and even pandemic modeling. For our call for research letters we had approximately, or more than 1,000 papers submitted, 414 of those were original research letters and about 265 as research letters. So I think it was truly a gratifying experience that we were able to provide a voice for the frontline cardiovascular specialists, providing what they were seeing, what they were doing, and also a perhaps a platform that was quick enough, dynamic enough for us to disseminate information. And also a platform for publications as research letters, which are concise and addressing the issue at hand and creating a portfolio by which all the investigators could voice their observations.
Dr. Amit Khera:
Well, listen, first and foremost, that was a heroic effort and a huge volume of different components, both research components, regional research articles, research letters, and then the videos. And I'll say those videos included fellows. I know I watched many of them before I went on service and taking care of patients to learn what people were doing. And that's so different than what we do in a scientific journal where we peer review and all that. And I can't tell you how helpful that was. And then something else you said was the personal experience. I remember watching a few physicians talking about what it meant personally for them and their families and quarantining and how hard that was and the human toll. And boy, that was really amazing. And I know we'll look back on those years to come and as we think about what COVID was when it first started.
Dr. Amit Khera:
I'll pivot a little to some of the science. I think having seen this from a different vantage point, at first you weren't sure how many papers you'd get. We were all looking for sort of kernels. And then all of a sudden there's a deluge of papers, right? Can you talk to that experience about how you learned how to curate all this when it was sort of started slow and then it was overwhelming?
Dr. Biykem Bozkurt:
We knew we would get a lot of papers. We didn't realize the true magnitude. At the beginning we thought that the assigned group, which we call the COVID editor group would be able to handle this. And thus we were trying to triage and provide a structured approach to this. It was quickly clear with James and Joe's and Darren's help that we needed the remainder of the whole editorial board. I remember initially we started with that small group and immediately expanded it to the larger group for us to be able to tackle.
Dr. Biykem Bozkurt:
I think starting with March, there was a steady rise in the types of papers. The interesting concept was the observations eventually start coming with a certain repeated theme. And of course the ones who provided the initial observations usually had the innovative part of the initial, the first one to recognize it. And there was a lot of debate. For example, when we were first seeing the papers about, or the research letters about the clots we were saying, or asking the questions, "Whether these were higher than the other ICU patients and so forth?"
Dr. Biykem Bozkurt:
But as the numbers increased, it was the summation of the gestalt of I think what the papers were providing was also moving the field. So not only the volume, I think that was a very interesting experience. Of course how to deal with that on an operational level, at a journal level. But also cataloguing and creating these, okay, these appear to be myocarditis, these appear to be potentially the clots. And then recognizing the how the story's evolving about COVID. And of course, intermittently we had the commission request and ask individuals to provide reviews that are with the insights, creating the synthesis from this culmination of this large volume of papers. And I think we try to do that in a timely manner periodically.
Dr. Amit Khera:
Yeah.
Dr. James de Lemos:
Actually just how hard it was to evaluate science in the midst of a pandemic. You know, what these investigators were doing in the midst of their surges was frankly heroic in the beginning. They were terrified, didn't know what was happening in their sites and they were submitting research. But the challenge is that it's not the kind of research we're used to evaluating in Circulation in terms of very well controlled clinical studies with good control groups and clear experiments. We were forced to evaluate research in a war zone basically and decide when something was actionable enough that we thought the clinical community could get ahold of it.
Dr. James de Lemos:
And at the same time we also had to think about our mission to publish durable science that will last beyond a few weeks or few months of the pandemic. And it was a real challenge and credit to Biykem and Augie here, who's running this podcast for the nights and weekends that we're done evaluating these and the many discussions about really what's the bar for research to get published in the midst of a pandemic. None of us and any of the journalists had ever been through this before.
Dr. Amit Khera:
I think those are great points. And I may even add to that just as much as there was the wanting to get things out that would help clinicians on the front lines, also responsibility of not publishing something erroneous where people would do the wrong thing. And we've certainly seen that along the way. So that was an added challenge. James, I'll pivot to you a bit more on this, in reflection, if you think about the papers now that you'd be able to look back, what are some of the ones that you remember the most, or you think were most impactful published in Circulation so far?
Dr. James de Lemos:
Well, some of the ones at the very beginning that were really written with almost a 24 or 36 hour cycle to get information out, there was a research, a review paper rather by Nick Hendren and Les Cooper that really came out almost the first weekend after this group launched. Biykem was involved in that. It was a remarkable effort to summarize really weeks old data on the potential cardiovascular complications. And it was an instant classic. Another one I think that has been tremendously important and durable was the report from Bonnet's group in France on the MIS-C syndrome in children that has been really paradigm changing. I think it was, it won the Willerson award as our top clinical paper of the year because the editors and editorial board felt that this was the most impactful paper we published of all papers in the year. And I think it certainly was amazing work to pull together that kind of series in such a short period of time and define a syndrome really that had never been reported before.
Dr. Amit Khera:
Yeah. You know, I'm looking here out of the maybe near a 1,000 papers or so of different varieties that came through, those are certainly two very memorable ones and several others. Biykem, I'm thinking about some other articles and even some really interesting frame of reference pieces that people, just sort of personal reflections. What are some of the ones that you remember?
Dr. Biykem Bozkurt:
The sequence of how it evolved is truly, left a sort of enduring impact on me. The first one that I remember was Kevin Clarkson's paper that provided the initial review, and we all were reading that, of course. Nick Hendren and of course Mark Drazner's paper also added a larger framework of the whole spectrum of cardiovascular disease or cardiovascular abnormalities with COVID. We, I think, try to provide a right balance in terms of the research papers and have received a large scale of papers on DVT and PE. And we then clustered quite a few of those. One of which was from Wuhan, China and the others were from U.S. And that became a very nice complimentary portfolio of three DVT PE papers, which I thought was very helpful at that juncture, because that came a little bit later in the timeframe. I can't recall, I think it was around June timeframe where we were able to formulate, really, this is truly a pattern.
Dr. Biykem Bozkurt:
The other very interesting paper that I remember is a series of echocardiographic imaging of all hospitalized patients from Israel. This was published in July. This was one of the first structured screening by echocardiography of all comers to the hospital. And it was about a 100 patients and it was by Topilsky. If I remember correctly, it was published in July. And that was the first one stating that a large number of patients had abnormality in the cardiac structure and predominantly RV, which until that time it was anecdotal case reports. We were all hearing about the RV and PE.
Dr. Biykem Bozkurt:
Then I think in July we had Peter Lewis' very nice review. And of course, Damien Bonnet's the multi-system inflammatory syndrome in the pediatrics, especially how to manage it. We also had a HRS partnership on guidance for how to do EP studies during the time of COVID, and a variety of frame of references. Some of which were about certain different approaches. We had one paper about senior woman leaders as to how they were supporting their colleagues. We also had early career faculty members who had provided their frame of references about social consciousness and ethical dilemmas, all of which were a true complimentary portfolio, providing not only the scientific expertise about human factor in managing this.
Dr. Amit Khera:
Well, you certainly have a great perspective on all the articles that came through, Biykem, and listed several of the highlights and James, I'm going to pivot you and ask you, what comes next? As one of the senior editors along with Biykem for Circulation, what do we need to see next in cardiovascular space or literature as it relates to COVID? I appreciate there's also what's happening with COVID in general, but what do we need to know and what's the level and bar of science now?
Dr. James de Lemos:
The bar is back to requiring excellent science, even for COVID cardiovascular disease, really. Because we know enough about the disease that we need the best information that's clinically actionable and meet sort of usual circulation standards. And what I'd say we need next is we need long-term outcome data. So we have a lot of information about short-term cardiovascular complications of the illness, but the next wave, and we're going to get through this, right? The end, the light is on for the end of this thing. But then the next phase is what's the long-term implications of cardiac injury that occurs in the hospital? What are the cardiovascular manifestations of these long haulers? And I think that will be the kind of research that's durable really over the next few years.
Dr. James de Lemos:
I'm very, very hopeful that we won't be talking about hospitalized COVID in 2022, that that will run its course and not be a dominant theme in Circulation. But I do think we're going to need long-term follow-up of cardiovascular issues for these patients. Particularly given the subtle cardiac abnormalities that Biykem was talking about that we've been reporting in the hospital.
Dr. James de Lemos:
The other piece I would just say is that we know almost nothing about cardiovascular manifestations of non-hospitalized COVID. Almost everything that we've published and other journalists have published has been about the minority of patients that get hospitalized. But we do need to know more about the many larger proportion that never get hospitalized.
Dr. Amit Khera:
That's a nice segue when we talk about sort of high quality science and maybe slowing things down just a bit to make sure we're getting the best answers. And that's a pivot to the AHA COVID-19 Cardiovascular Disease Registry, something which you have co-chaired and spearheaded. And we recently had a milestone at DHA scientific sessions. We had the first output just in a few months to already have some high-quality research coming out, we're going to hear in just a bit from two of our featured articles that were leg breaking science out of that registry in shortly. Tell us a little bit about the inception of that registry, what led to it and sort of how did it form?
Dr. James de Lemos:
Well, the impetus was really the same as what Biykem was talking about with her nights and weekends trying to generate information for practitioners. It was that feeling of powerlessness that we all had early on, knowing that this surge was coming, developing in other parts of the country and realizing that we knew nothing and all of us felt the need to fight back. And as you know, Amit, this really grew out of work of our young people that we developed, or I should say we, meaning our fellows developed a program to teach us about COVID and to study COVID in the patients at our two teaching hospitals. And that really led us to realize that the field needed generalizable knowledge that was beyond single center experiences and their work really directly led to the idea to approach the American Heart Association about a multicenter registry and then Sandeep Das, one of our associate editors and a faculty member at UT Southwestern and I pitched this to the AHA and then we put together a great steering committee and launched this.
Dr. James de Lemos:
And I think the unique thing about this that we tried to do was in the same, we recognized that the window for discovery was short and the usual way of registry research wouldn't work. And so what we did is we democratized the process. So we allowed multiple teams of investigators to be doing science simultaneously on a secure platform at the AHA, the precision medicine platform. And that's allowed dozens of projects to forward in parallel so that within this six month timeframe we have these two papers published, but we've got a lot of other, what we hope will be important work that can still make a difference in the pandemic.
Dr. Amit Khera:
Well, thank you for that. And I won't steal this under the upcoming articles to talk more, but congratulations to you on seeing this come to fruition, all the fruits of your labor in a very short amount of time. So we look forward to seeing many, many more papers coming out of it. I want to wrap up by just saying, I know we are certainly not done with the COVID pandemic, but it is a new year by the time this podcast comes out. And so we want to make sure we have time to reflect on what lessons were learned. What we learned about scientific publishing in these really trying times. And I want to congratulate you both on coming up with some very creative strategies to be as contributory as possible to what the field needed at the time. And I think you achieved that and we look forward to continuing to learn from Circulation and from the work coming in about this pandemic and many more things to come. So thank you both for your time today.
Dr. James de Lemos:
Thank you.
Dr. Biykem Bozkurt:
Thank you.
Dr. Amit Khera:
So now we're moving on to the featured article. This is the first of two, and I'm fortunate to be joined by my colleague here, Dr. Fatima Rodriguez, who's an assistant professor at Stanford in the division of cardiology. Welcome, Fatima.
Dr. Fatima Rodriguez:
Thank you so much, Amit for the invitation.
Dr. Amit Khera:
Well, you had this really important article on racial and ethnic differences in presentations and outcomes in those hospitalized with COVID and certainly there's been a lot about racial and ethnic differences. Tell me a little bit about the genesis of this particular article. What made you decide to use the registry early on as one of the first studies to evaluate this registry?
Dr. Fatima Rodriguez:
So as you heard from Dr. James de Lemos and Sandeep Das, the American Heart Association very rapidly created this registry to democratize and accelerate the way we do research during the pandemic. And this topic of racial ethnic disparities was right off the bat selected as a priority area because of the inequities that we're seeing, and that have been magnified by the COVID-19 pandemic.
Dr. Amit Khera:
Well, there's so much that you found and when it came to who was affected and who ended up in hospital with COVID and then obviously exploring some outcomes, maybe tell us a little bit about what are some of the main findings of this work?
Dr. Fatima Rodriguez:
We had a lot of significant findings, but I would say that some of the most important findings is that black and Hispanic patients really accounted for over half of the hospitalizations and the deaths in the registry during this first data cut. A third of the patients that were hospitalized were Hispanic and a quarter were black. Asian patients that we also studied had more severe presentations when they were admitted to the hospital. We were also surprised that race and ethnicity itself was not independently associated with worse in-hospital outcomes or other adverse cardiovascular outcomes. But again, this suggests that we really need to move upstream from hospitalizations to deal with the factors that result in the higher rates of hospitalizations for these underserved communities.
Dr. Amit Khera:
You know, I think you just summarized it so well. And I think for many of us that saw this paper, we saw that there was no difference in in-hospital outcomes in general and after adjustment, which I think that was a little surprising. Maybe we shouldn't have been surprised. Or do you think that perhaps looking at all the sort of media and the press about adverse outcomes we should have thought differently, or do you think this is the actual finding that one can expect?
Dr. Fatima Rodriguez:
Yes, we were surprised as well. And our hypothesis was that race and ethnicity would be independently associated with worse in-hospital death, but also mace. But it actually turns out there have been many publications across many different sites in the United States that have documented similar findings. Again, the caveat being here is that these patients were hospitalized and as a clinician you and I know that once people get in the hospital, at least for a disease like COVID-19, the care is fairly protocolized. And more of the variation mortality has to do with where these individual patients are hospitalized. And again, not surprising with the new disease that there's a lot of in-hospital variation. So not to say that there aren't disparities, but at least the hospital itself does not seem to be a cause of disparities and outcomes by race and ethnicity.
Dr. Amit Khera:
I mean, that's an incredible important finding to your point about once you get to the hospital people seem to do comparably well. So I think you said this in your conclusion as well. We really need to work upstream and is also profound that 58% were Hispanic or non-Hispanic black that were hospitalized with COVID. What are some of the upstream things we could be doing?
Dr. Fatima Rodriguez:
Yes, and this finding has been consistent across many studies. And I think that this reflects the over representation of these communities and the essential workforce, right? People that are not able to isolate. People that need to show up to work every day. People that live in multi-generational households and therefore exposed to the virus and higher rates of transmissions. So first I would say we need to try to do things to prevent the transmission in the first place in the communities. For essential workers they need to be provided the protective gear to again prevent them from the transmission. And now things are different then when we did this study. Now we have a vaccine that's about to be rolled out that we were discussing before, and we really should prioritize these communities in the vaccine rollout as well.
Dr. Amit Khera:
All great points. And as we drill down a little deeper into some of your findings, I think one that really stuck out to me was how much younger the Hispanics and non-Hispanic blacks were. I think average age of 57 and 60 versus 69 in non-Hispanic whites. Tell me a little bit about your thoughts on what is driving that younger age as well?
Dr. Fatima Rodriguez:
Yes, I agree that that was a fairly striking finding, especially Hispanic patients were on average 57-years-old compared to non-Hispanic whites who were 69-years-old when they were hospitalized. So more than 10 year difference. Again, I think a lot of this reflects the nature of the workforce and help individuals are higher rates of getting exposed, but also likely reflect some of the underlying co-morbidities. Remember, these are patients that are sick enough to require hospitalization. And again, we know that individuals that have higher rates of diabetes, obesity, and other risk factors have a higher tendency to be hospitalized.
Dr. Amit Khera:
You know, you also looked a bit at Asians, I should mention that. I think some of the findings were increased respiratory complications and perhaps some issues related to delayed some of the observations around Asian patients.
Dr. Fatima Rodriguez:
So the Asian patients did comprise a smaller portion of our registry, but again, still a notable finding that they tended to be sicker at time of presentation. We developed a cardio-respiratory disease severity scale specific to COVID, modified from the WHO scale. And again, found that patients even after adjusting for all other factors did tend to have a higher disease severity when they came in. One of the hypothesis of why this was the case is that they tended to have longer delays from symptom onset to both hospital arrival and to the diagnosis of COVID-19. And our study didn't look up why, but there have been some other studies that have suggested perhaps that there's been some hesitation in the Asian community to seek medical care for a variety of factors.
Dr. Amit Khera:
You know, and I think as we try to think about what are some implications of this work and what are next steps that could be one is to how do we enhance understanding of the need for prompt care in the Asian community, that could be one take home. One other tantalizing finding was this observation of less Remdesivir use amongst non-Hispanic blacks in this study, you made a point of that. What do you make from that, and what are some of the reasons you think are for that?
Dr. Fatima Rodriguez:
Absolutely. And we were interested in looking at how COVID-19 specific therapies varied by race ethnicity. And of course, things have changed dramatically in this area. As an example, Hydroxychloroquine was the most frequently used drug, and we know we don't use that right now in practice because it's not recommended. However, and Remdesivir is one of those drugs that does have fairly good evidence to use. And we saw that less than 10% of patients in our registry were on Remdesivir during the study period, with black patients being the least likely to be on this drug. Part of this may be explained by the lower rates of clinical trial participation among these patients, and then the other may be just higher rates of comorbidities. But again, might preclude the use of this drug. And we actually have a paper coming out from our registry, exactly looking at the differences in clinical trial participation by race and ethnicity.
Dr. Amit Khera:
Well, certainly look forward to seeing that. I think that would be an important followup to this. So I guess, leaving you the last word. This was I think a really important finding, helping us understand where the problem is, if you will. Actually there's numerous problems, but your point about upstream focus. So what's next? What do we do next in this field in terms of helping eliminate these disparities that we're seeing in COVID-19?
Dr. Fatima Rodriguez:
Yes, our hope when we started this registry is that we would have nothing to say at this point, this far along in the pandemic. I will also say one point that we didn't discuss is that mortality was high, and it was high among all groups. So we still have work to do in the inpatient setting to lower mortality, especially as the pandemic continues. But again, our work really suggests that we need to move upstream and focus specifically on vulnerable and marginalized communities, such as racial ethnic minorities to try to prevent the high rates of COVID-19 infection, and in particular high rates of severe COVID-19 infection.
Dr. Amit Khera:
Well, that was a fantastic review. And congratulations again on this leg-breaking science at the AHA sessions and one of the first early manuscripts coming out of the AHA COVID-19 registry. So thank you again, Dr. Rodriguez. It was a true pleasure to have you on today.
Dr. Fatima Rodriguez:
Thank you so much, Amit.
Dr. Amit Khera:
And now for our second featured article, we have Dr. Nicholas Hendren, who's chief cardiology fellow at UT Southwestern Medical Center and Dr. Justin Grodin, who is an assistant professor in the heart failure transplant section at UT Southwestern Medical Center. Their articles entitled Association of Body Mass Index and Age With Morbidity and Mortality in Patients Hospitalized With COVID-19, also from the AHA registry and also a late breaker at the AHA scientific sessions. Welcome gentlemen, and congratulations to you both.
Dr. Justin Grodin:
Thank you.
Dr. Nicholas Hendren:
Thank you.
Dr. Amit Khera:
Well, I'm going to jump right in, this obviously was a really exciting article. One, because of course it's timely with COVID. Secondly because it's one of the first science outputs from this AHA COVID registry, so we're all very excited about it. And importantly, really impactful findings I felt. So maybe I'll start with you, Justin. Tell us out of all the different questions and people were working on this registry, how did this sort of move to the top? What was the impetus behind this question?
Dr. Justin Grodin:
Well, I mean, I think the answer really lies from clinical experience. I think as you know, Amit, and as Nick knows, we quickly understood as the pandemic evolved that in addition to what we would call more traditional risk factors like cardiovascular disease, diabetes, hypertension, et cetera, and old age, we noticed that the young individuals that were hospitalized with this disease were actually more likely to be overweight or obese in comparison with their older counterparts. So really based on those empiric clinical observations we hypothesized that that would certainly influence outcomes for those that are in the hospital or ill enough to be in the hospital with this disease. As most COVID research has gone, we're basing kind of a hypothesis based on pure clinical assertion. So that was really, the origin was very organic and really based at observations made at the bedside.
Dr. Amit Khera:
I think that makes a lot of sense, and as you pointed out, with COVID drinking from the fire hose initially and hearing a lot of reports about interplay of obesity. But I think the value here of the registry was which was systematic curation and acquisition of patient data. So definitely makes a lot of sense why you pursued this. And I think what you found first and foremost was that the prevalence of obesity was higher in your patients hospitalized with COVID than those from exchange of the U.S. population. And then I'll turn to you, Nick. Tell us a little about what you all discovered, what happened with these folks with obesity? What was the course? What were some of the findings?
Dr. Nicholas Hendren:
You know, as Dr. Grodin mentioned, we were really interested at the intersection between the obesity epidemic and the COVID-19 pandemic. And they're major questions focused on two parts initially, which is, are people who are obese at increased risk of dying in the hospital? And the second part being, if you're hospitalized and obese, are you more likely to be intubated? And the answer to both of those after adjusting for the traditional risk factors like age, renal function, et cetera, were yes. And so what we observed was that people who are younger than 50 and severely obese, that means a BMI greater than 40, were at increased risk of dying. And that includes young people who otherwise might not think that they were high risk of dying. And then we observed that your body mass index, if you're obese, again a BMI greater than 30, puts you at increased risk of ending up on the ventilator unfortunately.
Dr. Amit Khera:
So really I'm going to dig deeper here as you all did in this paper. At first, obviously the prevalence of obesity was higher. Secondly, as you pointed out certain complications like being on the ventilator and I think VTE and other complications, and then some really interesting finding was this interaction with age. Maybe, Nick, tell us a little bit more about that age interaction.
Dr. Nicholas Hendren:
I think a lot of people are familiar with that age is one of the strongest, if not the strongest risk factor for dying from COVID-19. And what we were interested in was, if you adjust for age and try and take away the association between age, what is the risk of obesity in and of itself? And so we looked at patients that were less than or equal to 50 years old, kind of 51 to 70 and older than 70 years old. And really wanted to look at for those individuals that are obese in those age groups, what are their outcomes? What is their risk? And what we observed was that if you're older than 70 and obese, your risk of dying is probably not all that different by BMI. But if you're younger than 50 and obese, your risk is significantly higher if you're obese than if you were normal weight for that age group.
Dr. Amit Khera:
It's pretty fascinating this age interaction, that obesity seem to be more of a bad actor, if you will, in young people than it was an older people. And Justin, why do you think you find that? What was the rationale or biology there?
Dr. Justin Grodin:
You know, Amit, I think that's a great question. And that's a question that we were asking ourselves. As with other diseases, individuals that are more obese tend to be younger in general. So it's very unusual to see somebody that's older that is otherwise obese. So we do see a little bit of an imbalance in the age distribution, favoring higher obese groups in those that are younger. And that certainly could have influenced some of the observations that we saw. And then I think what's perhaps more interesting is, really what makes these young people that we would otherwise think would be low risk, high risk? What is it about obesity that portends a higher risk with COVID-19?
Dr. Justin Grodin:
And Nick and I, we speculated in the manuscript and really the reasons are threefold. At least we think, obviously it could be more than that. But number one is that we all know that obesity can be associated with metabolic diseases, diabetes, and whether or not there's some subclinical or undiagnosed form of that that is also contributing to risk in these people mediated by obesity could be one possibility.
Dr. Justin Grodin:
The second is actually directly related to the SARS-CoV-2 virus itself in that the ACE2 receptor is actually abundantly expressed in adipocytes. And so we know that obese individuals have more adiposity perhaps putting them at higher risk. And then the third reason is that individuals that are more obese actually have just more mass on their thorax and that might influence some of their pulmonary dynamics and might put them at increased risk for adverse events.
Dr. Amit Khera:
All certainly great hypotheses, and obviously further things to test. I'm looking at your conclusions and essentially you reminded us that preventive strategies in obese people regardless of age is something we need to focus on. So I think that's a really important take home point. Last question. Do you, Nick, I want to first congratulate you. I know way back when we were just thinking about the problem of COVID and begin to collect our own data and that germ of an idea really snowballed into this idea of the AHA COVID registry, and you had a critical role in that. I remember talking to you and you were putting in data on nights and weekends. How does it feel now to see the output of your work really so quickly and so such impactful work after doing all this labor and working so hard to get this up and running?
Dr. Nicholas Hendren:
Well, I think anytime you're able to have at least a small amount of success or something that's felt to be valuable to the contributions, it's always a nice thing. And it was such a team effort all the way through and from the American Heart Association to our attendings, Dr. de Lemos who spoke earlier and Dr. Grodin and all of our team members. And so it's really impressive how the entire field of medicine and cardiology has come together and try and battle COVID across all lines. And so to contribute to that in even a small way is hopefully helpful. And hopefully people will read our information and make choices that will help keep them safe and keep people out of the hospital and doing well off the ventilators.
Dr. Amit Khera:
Well, thank you. And congratulations to you both on a really fantastic work and impactful paper. And that's it for me, I'm Amit Khera, digital strategies editor for Circulation covering for Carolyn Lam and Greg Hundley, who you'll hear from next week. Thank you all for enjoying our podcast today.
Dr. Amit Khera:
This program is copyright of the American Heart Association 2021.