Dr. Daniel Simon (Host): Hello, everyone. My name is Dr. Daniel Simon. I am your host of the Science at UH Podcast, sponsored by the University Hospital's Research and Education Institute. This podcast series features University Hospital's cutting edge research and innovations. Thank you for listening to another episode.

Today, I am happy to be joined by our guest. Dr. Sanjay Rajagopalan, Chief of the Division of Cardiovascular Medicine, the Chief Academic and Scientific Officer at the University Hospital's Harrington Heart and Vascular Institute, and the Herman K. Hellerstein Professor of Cardiovascular Research. Sanjay is a world-renowned expert on the health impact of pollution, climate change and the intersection of environmental factors with cardiovascular health. Welcome, Sanjay.

Sanjay Rajagopalan, MD: Thanks, Dan. It's great to be here with you.

Host: Last year, a new study for your team was published in the Journal of the American College of Cardiology connecting the 1930's redlining to poor health outcomes today. It's really incredible that a federal government created loan risk program where a green or A was best all the way down to red or hazardous to find neighborhoods back in the '30s. And believe it or not, those redlining districts all the way back from the '30s are now linked to poor health outcomes decades later today. I mean, it's just incredible. It's very, very sad. And I want you to tell us a little bit more about these findings and what factors do you think drove these associations?

Sanjay Rajagopalan, MD: Thanks, Dan. And it's great to be here with you and talking about this very important topic. Equitable health, as you know and as the audience knows, is a topic that's been in the national conversation for a while. We live in the richest country in the world, and yet we struggle with deep, deep health inequities that are so extreme that one cannot help wonder why this is happening here in the United States.

To give you an example, in Cleveland alone, there's a 20-year life expectancy difference between individuals living on either side of Van Aken Boulevard. Sadly, this is just not an Ohio phenomenon, but something that's seen in most states, including Massachusetts, where in Boston, home to some of the best institutions for health in the world, there's more than a 20-year difference between somebody living in Back Bay, a wealthy community, and Roxbury, a poor community. We now know that this is just not about access to healthcare, but a myriad of factors in the social and physical environment.

The study that you mentioned, as you talked about, is in the practice of redlining, which is a remnant of racist policies that continue to have an impact on health outcomes still today. The government-sanctioned HOLC, or the Homeowners Loan Corporation, and policies that was instituted resulted in deep, embedded inequities in black neighborhoods throughout the United States, be it from a want of trees, poorly designed neighborhoods, areas of the city that are less desirable as they were situated next to toxic waste dumps or electric power lines, or were close to highways, and in some cases highways are literally made to run through these neighborhoods. But these same neighborhoods also have poor access to healthy foods, a lot of fast food restaurants, very few trees, lack pavements, and even reasonable access to healthcare. These same embedded factors constitute what we refer to now as structural racism, not surprisingly correlate with poor health outcomes until today.

 As you point out, we've shown in this paper and a few others, the redlining is associated with high rates of hypertension, diabetes, obesity, chronic Kidney disease, stroke and heart attacks. And importantly, we've also shown that this extends in many other papers to even veterans living in redlined neighborhoods and those with other health disorders.

Host: Well, you know, Sanjay, something that I know that your team is working very aggressively on through a variety of grants that we'll talk about during the course of the podcast to really understand these health inequities and disparities and try to come up with solutions that will narrow this life expectancy gap. So, your findings clearly suggest an important impact for poorly appreciated factors in the built environment, the natural environment, as well as the social environment. How do you think these understanding of the links between the environment and health can result in better outcomes for individuals and for populations? And I think, you know, I want to focus specifically on your work related to air pollution and its impact on heart, cardiovascular outcomes.

Sanjay Rajagopalan, MD: Great. Thank you. You know, the fact that the environment, and by the way, I sort of used the word environment. When I use the word environment at least, I do mean the sum totality of externalities and several internal factors outside of genetics that really correlate with health outcomes. This would include factors in the natural environment, temperature, humidity, trees; built environment, which includes things like food, consequences of energy supply, energy distribution, and you mentioned air pollution as one of them, transportation, connectivity; how people get around, whether or not they use highways or, you know, what kind of transportation they use to get to work and for recreation; building, sanitation, water supply, the whole enchilada. All of these factors that lie at the crosshairs of human health result in multiple adverse health exposures. And I use the word exposures, meaning that these are the kinds of things that people get exposed to during the course of their livelihoods, including air pollution, soil pollution, water pollution, adverse nutritional risks, climate risks, social factors, which are also indelibly linked to some of the environmental exposures that include the communities that you live in, the friendships that you have, these also are well known influence risks. Economic factors, poverty is a big factor. And finally, internal factors, as I mentioned earlier, factors such as sleep and stress, how we handle stress, are also increasingly recognized as critical arbitrators of health.

Now, the reason this is important is because many a time and many of these factors are completely preventable. Air pollution, for instance, causes more than 9 million deaths a year, is a fourth leading cause of global mortality and disability. And it's completely preventable as are deaths related to poor food choices. Again, but some of it obviously has the element of behavior and proportion. But again, you know, in a perfect world, these are preventable choices that people can make. Limited physical activity certainly, I think, is a huge, huge factor responsible for this massive epidemic of type 2 diabetes mellitus and obesity that we are currently experiencing.

The point is by understanding the links between the environment and health, we can transform delivery of healthcare and better health outcomes for our patients. And by understanding these links, we can help avoid a number of these tragic consequences that we now see played out in the health environment.

Host: Well, you know, Sanjay, I think it's a real cold water, ice water on us when we start thinking about this notion that there are 9 million deaths in the world from air pollution that are potentially preventable. And it really gives us pause as cardiologists who focus intensely on blood pressure, our LDL cholesterol, our family histories, diabetes, smoking status, and yet, you're telling us that one of the biggest factors responsible for outcomes in many of our patients is going to be something air pollution, which is obviously man-made, difficult to control, but we certainly are trying. Let me ask you this, you've talked about some other important variables, namely temperature and tree coverage, walkability and other things. What are the things, the top three maybe, that you would say to our listeners that we should really focus on for the biggest bang for the buck?

Sanjay Rajagopalan, MD: Great question. As I mentioned before, this happens to be a very fortuitous time for us to make some radical transformation in health. The recent focus in climate change, and as all our listeners know very well, there are intimate links between air pollution and climate change. In fact, same sources and the same emissions that result in global warming are also responsible for killing nine million people. So, there is really a tremendous opportunity for us to transform energy sources so that we move to clean energy fuels to power our homes and transportation. And that can, in the next 10, 15 years, have a huge impact on the mortality attributable to air pollution.

And while we are at it, there's also a tremendous opportunity for us to redesign the neighborhoods that we live in, rethink how we live and how we recreate and how we spend our time, make our roads more walkable, have abundant areas for recreation, increased tree cover because there's a fundamental link between trees, for instance, and health in general, and a number of reasons why this might be. But we need to reunderstand the larger fabric that holds together humanity, animals and trees together on this planet and restore the historic symbiotic relationships between man and the environment to restore planetary health. And I think we have a tremendous opportunity to do that. There's literally billions, if not trillions, of dollars going into changing our energy sources and supply. And together with that, there's also a radical rethink in how to redesign the environments that we live in. And together, I think we can make a tremendous impact on prevention and preventing some of these preventable disorders like hypertension, obesity and type 2 diabetes mellitus.

Host: You're giving us a new language and a new vocabulary to think about. it recalls just a trip I made only about a month ago for a board meeting in Paris. And I was challenged by some of our French colleagues, they asked me if I knew what my annual CO2 footprint was in a year. And of course, I had no idea. They told me that the average French citizen produces about 9.2 tons of CO2. And that the goal in France is to get down to the two to three range. Now obviously, France is a little bit of a different country because it's mostly powered by nuclear, so they have a lower footprint. But I was shocked to learn that Americans, the average American, produces over 25 tons. And obviously, I have a lot to learn because I really had no idea about this discrepancy, and the impact of our choices, and most importantly, for instance, air travel on that CO2 footprint. So, we all need to learn, but I think that you're teaching us that we must do this if we want to enhance lifespan for all citizens in our community.

Now, congratulations to you and your CWRU collaborators and those, of course, also from Wayne State on many very large mega grants that you're involved in; an $18.5-million grant related to social determinants of health from a cardiovascular standpoint and a new grant, $6.2 million from NIH to really look at artificial intelligence's ability to predict cardiovascular risk. And this really grows out of some incredible work that you and I have been involved in now for many years, started by our dear colleague, Dr. Carl Orringer, leading us to the importance of coronary artery calcium scoring and, under your leadership now, performing more than 20,000 scans a year for free or no charge to our community to predict our risk for heart disease. Tell us a little bit about this new $6.2-million dollar grant and how you think this will improve both population and precision health at the same time.

Sanjay Rajagopalan, MD: Well, as you know, you were very much part of the inception of the program. In fact, I'd argue as much of an architect for this transformative program along with Dr. Orringer, which is by far, to my knowledge, the biggest commitment that UH has made to the health of Ohio citizens. Dan, I really can't think of any other program which has had such an impact in putting patients in control of their health. We've already shown improved outcomes of the program in terms of risk factor control. And we're talking primordial prevention, which is a best bang for the buck. No comparisons, right? It's just singularly important. And we've also embarked on taking this a a step further by bringing a personalized record of the calcium score report to patients to ensure that they are in control of their health and take control of the implications of the findings.

So, the next phase of the program, as you mentioned, is now in a research phase, which is to understand whether there are features to use a machine learning AI terminology, features or aspects of any picture on a CT scan in this case that might tell additional stories. And now, we're utilizing advanced machine learning and AI tools to uncover patterns or features on a CT scan, which can tell us a whole lot more about the patient's risk. And by extracting over 4,000 features from the CT scan and utilizing deep learning tools, we're now developing precision medicine approaches to predict health in better ways than we've ever done before. We're also combining this with place-based information. In other words, combining this with where people live with a range of other exposures or factors, including built environment, the neighborhoods, social and other environment information that's now available thanks to big data from the web to develop precision analytic tools. And we'd probably have to organize another time to talk about this on different podcast, but all very exciting stuff.

Host: Wow, Sanjay, you know, it's incredibly exciting to see our ability to help patients look down the road, tell a patient you are at a very high risk for a vascular event, a 25% risk of cardiovascular death, heart attack, and stroke, but that you can mitigate this risk by personalized attention with your doctor and caregiver to reduce that risk down into low single digits, by optimizing risk factor control. That's a great, great development for patients in our community. Now, I have a question for you. You know, you were like me, a basic scientist, at one point who was focusing not only on the internal environment, but on the cellular and subcellular environment. And of course, now, you're considered one of the world's experts on the external environment. I'm just curious, what inspired you personally to take this deviation and dive into the external environment? What was the aha moment for Sanjay?

Sanjay Rajagopalan, MD: Well, you know, I, like all of us, you know, we are seekers. We're looking for larger cues, you know, around you and the world around you to make an impact. And I firmly believe, and for a long time, I've always believed that there was something off between our pursuit, relentless pursuit, for, you know, more understanding of deeper molecular mechanisms and a disconnect between how do we translate these findings to the external world. And also, there was a feeling that many of us have, which is we really want to make impact in the limited time that we have and what can you do that has the biggest impact? And again, I would say that many of the opportunities that I've had in my own life have been rather fortuitous. It's been working with very generous individuals. And folks that have had larger views of the world than myself that I've learned from them. But really, these opportunities sort of present themselves to you and sometimes you take advantage of those. And I firmly believe now that a bigger, I guess, perspective for why I'm here is to try to make the connections between what you're doing at the basic science level to impact population health in a big way.

And I think the connection between the internal environment and the external environment so much so that there is no difference. You know, really from a quantum perspective, it's all connected. And what's happening inside is inevitably connected to the outside. I'm sure some of your audience must have heard of the saying, "The flapping of the wings of a butterfly can be felt on the other side of the world," right? So, this Chinese proverb implies that very small actions are capable of generating very large changes in ways that you would not even imagine, right? And hyperlocal events can have global impact, just like simple things in the subcellular level has a larger impact on the organism level or the organ level. Similarly, your actions that you do locally can have tremendous impact outside. And in that sense, I think the work that we're doing, hopefully, is to further the idea that whatever we do, we'll have to do this thinking about what we can impact locally. And, some way or the other, these actions are capable of transforming and creating larger change.

Host: Sanjay, I have to say, for our listeners in the podcast, this is the exact reason why we recruited you to University Hospitals and Case Western. What an honor and a privilege it is for me as the inaugural Herman K. Hellerstein professor to have passed that off to you and watch you soar and take that professorship to a new level.

I wanted to just conclude with a final program that many of us have taken advantage of, which is the Center for Integrated and Novel Approaches in Vascular Metabolic Disease at University Hospitals, what we call the CINEMA Program, where we send all of our patients with type 2 diabetes, metabolic syndrome and frankly obesity for a revolutionary approach to managing risk. Tell us just a little bit about that program. I know that you've seen nearly 1,200 patients now and you're changing people's lives. How did you and Dr. Neeland and your team think about novel approaches for these very difficult to treat patients?

Sanjay Rajagopalan, MD: Well, there are a couple of things that I'd like to say. Number one, I think every good idea, you know, also takes some advocates and we've had some very important advocates at UH to take these ideas into consideration. One of the trends that we've been watching over the last 12 years, and this has been part of my own sort of interest in the area of obesity and type 2 diabetes, is this incredible revolution in pharmacotherapy, going back to early work done in the early 2000s that saw the approval of drugs called GLP-1 receptor agonists. And we recognized very early on that this has to be part of the therapeutic armamentarium, as also drugs like SGLT2 inhibitors. And importantly, there needs to be an all-encompassing where we deal with this risk with well formed, well educated and prepared teams that just doesn't include just a physician, but also the ancillary care providers that are so critical in disseminating information and bringing patients to take control of their lifestyle. Because pharmacotherapy works, but it works a heck of a lot better if you have an engaged patient who's also doing the due diligence in their part in terms of diet and exercise. So, we were fortunate to get this program started, and we also started a greater conversation in the country with larger organization called the Cardiometabolic Health Alliance, of which we are one of the strategic founding partners, and the CMHC is really one of the leading organizations in the United States, if not the world, that's really advocating an integrated approach towards managing type 2 diabetes patients at risk.

So, we've really leveraged a number of how should I say, happy, helpful findings as well as, you know, just read the tea leaves a little bit earlier than most other people and got this program started when we could. So, I think doing very well and I'm very proud of Dr. Neeland and the work that he's doing and everybody else on the CINEMA team.

Host: Well, you know, I have to say, Sanjay, I've sent now probably a dozen patients to CINEMA and it has literally changed their lives. We're talking about weight loss between 25 and 50 pounds; hemoglobin A1Cs 8s, now down to the 6s; and just a complete transformation, not only physically, but emotionally and even spiritually, feeling almost reborn from the standpoint of being able to really pursue health and wellness and sort of averting that severe decree, so to speak, of type 2 diabetes.

Well, Sanjay, I want to thank you for taking the time to speak with us today. Every time I speak to you, I learn a lot from you. Your work is transformative. It is very important and is literally saving lives every day. For our listeners interested in learning more about research at University Hospitals, please visit uhhospitals.org. Thank you for joining us today.