The Surprising Heart Disease Predictor You Might be Missing
OmegaMatters: Episode 44
Hosts: Drs. Bill Harris & Kristina Harris Jackson
Guest: Grant Franco, MD, Saint Luke’s Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO
About this episode: In this episode, Drs. Harris and Jackson welcome Dr. Grant Franco, the lead researcher in a recent paper showing that the Omega-3 Index is just as powerful a risk predictor for CVD as smoking and cholesterol. For more information on OmegaMatters, visit: https://omegaquant.com/omegamatters-broadcasts/
SHOW TRANSCRIPT
Dr. Bill Harris: Hello and welcome to another session of Omega Matters where we talk all things Omega. My name is Bill Harris. Normally, I’m joined by my daughter Christina Jackson, but she is dealing with a sick child today. So, life happens. So, I’m going to handle our discussion with our guest Grant Franco. Grant is working with the O’Keefe Group in Kansas City at the Mid America Heart Institute. He is an MD, and just about ready to continue some of his training at Wash U in St. Louis. Many times, we interview the most senior people in the field, and sometimes we get to interview some of the up-and-coming field, researchers, and I think that’s what Grant represents here. So, welcome, Grant, and we’ll have a talk about the PCE, which we’ll get to in a moment.
Dr. Grant Franco: Yeah. Super excited to be here. Just quick correction, I’m going to be going to St. Mary’s Hospital in St. Louis, not Wash U, but I’ll be right near there. But I’m super excited to be here. I’m excited about the research we’ve been doing, and really grateful to learn a lot from you guys, because you guys are real resources in teaching me how to write a paper, get a paper published, how to respond to all the stuff that you have to do to really become a prolific researcher like you guys are, and you are. So, thank you.
Dr. Bill Harris: Yeah. Well, yeah. You’ve got to learn the ropes.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: There’s certain skills for writing and publishing, and reviewing, and responding editors questions, and revising.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: It’s quite a process, and you did a great job on this paper. The paper we’re going to talk about today, I think I’ll just bring up a picture of it. So, this is the paper. It’s a brand-new paper, and it’s published in the Journal of Clinical Lipidology, one of the best … It’s a fairly young journal in a way, but it’s really a very good one. And we’ve published in it before. There is a William G. Go by Grant, though. Right?
Dr. Grant Franco: Yeah.
Dr. Bill Harris: Your middle name. Along with our other investigators and the title is the “Omega-3 Index Improves Upon the Pooled Cohort Equation in Predicting Risk for CVD.” So, that is the topic, and I think I want to maybe move that out of the way, and stop sharing. Let’s see. Stop sharing. I’m going to bring us back full-screen. And so, introduce us to the idea and what we did.
Dr. Grant Franco: Yeah. So, the idea is there is a paper that I believe you worked on about 15 years ago that looked at this Framingham risk score, which is using different risk factors to predict risk of developing cardiovascular disease, and, particularly, coronary disease. And it looked at looking at a real advance lipid suite, and see how that did for predicting CVD versus the Framingham risk score. And so, the general idea of the paper was to see how an Omega-3 index, or a blood level of our Omega-3 levels, and how that did fitting into the most current risk score, which is the Pooled Cohort Equation. A little background I guess about these risk scores is a lot of people have heard of the Framingham Heart Study, which, essentially, looked at all of the health of the members of his town over an incredibly long period of time, and it looked at different risk factors for developing coronary disease. Coronary disease meaning having a heart attack, or angina, or something like that. And looked at those different risk factors, and seeing how we could develop a risk, like, a 10-year risk for somebody having an acute coronary event, which would be a heart attack, or something like that. And so, that’s where we developed our thoughts about cholesterol, and this has been a very important thing. So, we developed this risk score that came out in 1998, and it’s been iterated on. Framingham, Massachusetts was not the most diverse place. And so, we’ve been iterating on this Framingham risk score to be more inclusive of different ages, and different socioeconomic backgrounds, racial backgrounds.
And eventually in 2014, we developed the Pooled Cohort Equation, which is an expanded upon risk score, which has been incredibly useful at developing a 10-year risk for developing coronary heart disease in 10 years. And the idea of this risk is you look at if you’re smoking, if you have diabetes, your total cholesterol, and your systolic blood pressure. Like, all these important things. And so, our idea was how can Omega-3 index make this score better? This is a very important score for determining if somebody who doesn’t have coronary disease, if we’re going to put them on a statin, or not. Are we going to treat cholesterol? And, particularly, if somebody has right between 7.5% and 10% risk of having an event in a 10-year period, it’s, like, you go on a statin, that’s how it goes.
And so, if we can even improve upon that a little bit, or we have some kind of tool to further discriminate risk, then that could be really helpful for clinicians, and, particularly, Omega-3 index, because it’s an … Like, I like to talk about it as low-hanging fruit, because when we’re talking about somebody going on a statin, or a blood pressure, these are things that usually are not … While they’re incredibly helpful, they’re not entirely benign. And often times, consuming more fish, supplementing with high quality Omega-3, these are rather benign things that can be incredibly helpful for people in their long-term health, and long-term risk of developing coronary disease.
So, that was the thesis, and idea. I feel very fortunate to be able to work with you guys, and have access to incredibly talented biostatisticians that have been able to work out exactly how this fits in. And we used a couple of the Framingham cohorts, the initial ones, I don’t know if it’s necessary to tell you all of them, but we used those initial cohorts and figured out that the Omega-3 index is actually a really powerful and predictive tool for seeing if somebody is going to develop coronary disease. And it’s interesting. A lot of the risk factors that they use in this score are dependent on each other in a way, and often times, when we … We did this study, and we found out that Omega-3 is actually this really powerful independent risk predictor.
Dr. Bill Harris: What are the components of the Pooled Cohort Equation to begin with?
Dr. Grant Franco: Yes. Yeah. So, it starts off with age, and age is this incredibly shockingly important risk stratifier. So, age is the first and most important one, age and sex, but really age. And then after that there’s systolic blood pressure. So, that’s how well your blood pressure is controlled. If you’re on blood pressure medication, your total cholesterol, and then if you have familial hypercholesterolemia. So, if your LDL is incredibly high. Also, if you have diabetes, if you smoke, and your race is included, but it’s actually not very important in terms of the risk score itself.
Dr. Bill Harris: Yeah.
Dr. Grant Franco: So, those are the main-
Dr. Bill Harris: HDL cholesterol is in there too.
Dr. Grant Franco: Oh, HDL cholesterol. HDL cholesterol, and HDL cholesterol is really important. Thank you for mentioning that one, because it’s really important, but it’s not very changeable. It’s good for determining risk, but we don’t have a lot of advice how they’re like, “Get somebody’s HDL from 40 to 60.” You know?
Dr. Bill Harris: Yeah. Right.
Dr. Grant Franco: But Omega-3 index is modifiable. And so, that’s why it’s an interesting thing to look at.
Dr. Bill Harris: Yeah. So, yeah. I think as we did this paper, I think we were all maybe not surprised, but it was quite an eye-opener to see how much of the risk prediction is just driven by age.
Dr. Grant Franco: Oh, yeah.
Dr. Bill Harris: And these other six or seven factors that you just went through, and each add a little bit, a little bit, a little bit, and the … But I think we forget that they’re only adding a little bit of predictive value. And so, when we added the Omega-3 index, how much did it change the prediction?
Dr. Grant Franco: Depending on how you add it on from two to … Like, 1% to 2% predictive value in this area-
Dr. Bill Harris: Okay.
Dr. Grant Franco: … under curve, which it’s, kind of, a … It’s hard to describe how we validate the statistical … Like, statistically validate tests. We use area under curve. So, you have a how much of the total disease burden did the test capture?And so, it, essentially, captured an additional 1% to 2%, depending on how you add it in. If you add it in initially, right after age and sex, it captures more, but if you add it in at the end, it still captures a fair bit of that I guess relative change to the AC … Yeah. So-
Dr. Bill Harris: How does it compare to having high cholesterol, or-
Dr. Grant Franco: Yeah. Yeah. So-
Dr. Bill Harris: For example. Yeah.
Dr. Grant Franco: Yeah. Compared to having a high cholesterol, when you add it in after cholesterol, it’s going to capture … So, it captures about 4%, and when you add it in after age and sex, and if you add in total cholesterol, it captures 2% extra. So, it’s actually capturing double the amount of cardiovascular risk over the 10 years when compared to total cholesterol.
Dr. Bill Harris: And we should just probably stop and marinate on that for a minute, because-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … I think most people you ask them what are the big risk factors for heart disease and they don’t say age. They don’t say sex. They say cholesterol.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: And maybe they say blood pressure. And that’s what they know. But you found in your study that the Omega-3 index was as, or even more, predictive of future risk for cardiovascular disease than cholesterol.
Dr. Grant Franco: Exactly.
Dr. Bill Harris: Which is a wake-up call, because people don’t think about Omega-3, as you mentioned, a very modifiable risk factor-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … as running with the big dogs in a sense. It’s just as good, or just as bad in a sense as the standard risk factors. And so, what would be the takeaway from this. I know you’ve expressed an interest in primary care, and how would this you think help out in a primary care setting?
Dr. Grant Franco: I think the accurate determination of risk for patients is really important. And like I said, having an easily modifiable thing that we can change without adding on a medication that is exposing you to risk … A lot of people don’t like taking statins. And if somebody is on this borderline risk area, and this 7.5%, we could think about, first of all, getting an Omega-3 Index, see how they’re doing in terms of their Omega-3 level, and then think about adding on a fish oil supplement, or an Omega-3 supplement on top of that.
Or if somebody isn’t as interested in that, making sure they’re consuming more oily fish. From zero to one to two to three times a week. These things are actually really helpful for patients, and, to be honest, patients like having options, and having agency in their healthcare.
And having a discussion that isn’t like, “Okay. You can do a statin, or not” is an important place I think to start for patients. So, I think this is an incredibly powerful tool, and it can be really helpful in getting people on a healthy track in terms of their diet.
Dr. Bill Harris: Yeah. I don’t think you’re saying this. You’re not saying that fish oil would replace a statin?
Dr. Grant Franco: Yeah. No. I’m not saying that, but what I am saying is that … Well, because this is we’re talking about this narrow range of risk in the future, like, looking at people’s risk into the future. And so, raising their Omega-3 index … Say, like, when we think about this, you start somebody on a statin when they’re between 7.5% and 10% risk in the Pooled Cohort Equation.
And if they’re in the lowest quartile in Omega-3 index, and they don’t want to do a statin, or, maybe even their cholesterol is pretty well-controlled, it’s, like, they have pretty good cholesterol, and they’re worried about being in this 7.5 … Say, they’re right at 7.6% on the Pooled Cohort Equation. I think giving a patient the agency to say, “Let’s try a dietary …” Something that actually might help, and they don’t want to do a statin, that’s helpful. But also being able to recommend … Say, they do want to do a statin, but they want to do more, you can say, “This is actually really important, and can also help you on top of it.” I think both things are important. Yeah.
Dr. Bill Harris: Yeah. It sounds like the same kind of approach you would take with somebody who has got high cholesterol and is a smoker.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: You’d say, “Well, there’s two things we can do here.”
Dr. Grant Franco: Yeah.
Dr. Bill Harris: “And should do.” Right?
Dr. Grant Franco: Yeah.
Dr. Bill Harris: “Stop the smoking and deal with the cholesterol.” And here you say you’ve got a
level Omega-3 index-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … that’s a problem and it’s fixable.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: It doesn’t fix everything-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … but it’s something you can do to improve your health, and actually lower your risk score.
Dr. Grant Franco: Yeah. Yeah. And to be clear, if it sounded like I didn’t want to put somebody on a statin if they had high cholesterol, it is one of the things in my current role that I pride myself in is talking people through going on a statin when they’re really scared to go on a statin. So, it’s, like, I care about that, but I also really care-
Dr. Bill Harris: Yeah.
Dr. Grant Franco: … about Omega-3 index, and I think it’s really important for people to think about the diversity of their food consumption. If they’re not eating fish, we should be supplementing Omega-3. Most people are not eating enough fish. So, most people should be supplementing Omega-3. And so, I think it’s really important.
Dr. Bill Harris: Yeah. Yeah. In your research background, research for doing this paper, did you find … We’re talking about 10-year risk prediction. And someone would say, “Well, I’d like to know my 30-year risk prediction.”
Dr. Grant Franco: Yeah.
Dr. Bill Harris: Has anybody done something like that that you know of?
Dr. Grant Franco: They are starting a new risk score that is … I don’t know specifically how long. I think it is 30-year risk. It’s a cardio, kidney, metabolic score, which they’re starting to roll out, which is actually a very exciting advancement I think in our risk prediction. And I think it’s probably the obvious future application of this research, but it’s inclusive of more ages. So, it’s, like, the PCE, you start being able to calculate risk at 40 years, when somebody is 40 years old-
Dr. Bill Harris: Oh, age 40?
Dr. Grant Franco: … younger, it’s inclusive of metabolic disease, socioeconomic status, and kidney disease, and because everything is so connected.
Dr. Bill Harris: Oh, wow.
Dr. Grant Franco: And I believe that one predicts 10-year risk, and 30-year risk. I hope that’s not-
Dr. Bill Harris: Yeah. Yeah. It’s hard to imagine how from a baseline today-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … predict your risk 30 years for heart attack, and actually prove it, because you have to not … The people whose lives are used to make those equations-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … theoretically have to live another 30 years, and they have to have not changed anything.
Dr. Grant Franco: Yeah. Yeah.
Dr. Bill Harris: Because if you stop smoking, you fix your diabetes, get your blood pressure under control, your liver is under control, your Omega-3 index, your risk really is going to be much lower than it was predicted to be, and you wouldn’t know that unless you tracked them all the way through. It’s a real challenge I think to look at these long-term-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … predictors. Yeah. And so, you mentioned this, there’s a new risk prediction that includes chronic kidney disease, which is interesting, and reasonable.
Dr. Grant Franco: Right.
Dr. Bill Harris: I guess the next step in this kind of research would be to take the Omega-3 index and add it on top of this new predictive thing, and see if it still predicts. Do you have any idea of what the mechanism by which the Omega-3s are working is that would maybe explain why it adds additional predictive value above and beyond the other risk factors?
Dr. Grant Franco: Yeah. There’s a number of mechanisms, and I know this is your total wheelhouse, but when I think about Omega-3 and what it does in terms of overall health and cardiovascular health, I think first about the anti-inflammatory properties it holds, and modest antiplatelet properties, it’s not … I wouldn’t say it’s Aspirin, but it has some modest antiplatelet properties. And so, like-
Dr. Bill Harris: What is that? What’s an antiplatelet property mean for-
Dr. Grant Franco: Antiplatelet … Thank you. Sometimes I can use jargon. So, antiplatelet … When you have a heart attack, what is happening? You have a plaque in your arteries, which is a inflammatory bulging out of your arteries that has this rich lipid core, and it breaks off, and it aggregates these platelets, which are the things that stop you from bleeding if you are bleeding. And they’re really important. You want platelets. But if you have an atherosclerotic plaque,
which is that thing that causes heart attack, and it breaks, and it aggregates all these platelets, and then you have a heart attack. And then you [inaudible 00:21:58] with the crushing chest pain. And so, one of the first things they do when you have a heart attack is you take 325 milligrams of Aspirin, and you chew it, and it’s one of these things that helps you. So, how people take a baby Aspirin-
Dr. Bill Harris: Yeah.
Dr. Grant Franco: … having some amount of antiplatelet activity in your body, and I think we can have a whole different discussion about that. There is a modest antiplatelet activity with Omega-3, and I think that probably helps a bit with these ASCVD events, or cardiovascular, or these coronary events.
But also inflammatory disease. I always talk about … This is how I explain it in our clinic to patients when people want to know what is a heart attack, what causes it, I, in a …
The example I use is when you fall and skin your knee as a kid, you’re running around outside, you skin your knee, you make a scab over that part that you skinned, and the same thing happens in your arteries. When things damage your blood vessels, there’s an immune reaction that happens and you make this thing called an atherosclerotic plaque over that damage.
And so, things like high blood pressure, high cholesterol, smoking, diabetes, all these things damage your blood vessels, and chronic inflammation is one of those things that completely and totally damages your blood vessels, and increasing your body’s anti-inflammatory capacity through high Omega-3 index will, certainly, help long-term risk in terms of developing these plaques in your arteries.
Also, and this is secondary to the risk of developing these plaques, also there is a lot of membrane health. When I think of Omega-3, I think of membrane health and increasing your cells’ ability to work together, and to receive signals, and to get all the things that they need. And so, it’s this really holistic cellular health mechanism when I think about Omega-3 and how it works.
So, those are the things that I think about when I think about how Omega-3 works. I know you’re completely … This is your wheelhouse, and what you’ve devoted an incredible amount of-
Dr. Bill Harris: Yeah. I like to hear other people-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … explain it, and make sure the message has gotten through.
Dr. Grant Franco: Yeah. Yeah.
Dr. Bill Harris: To the next generation.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: I appreciate that.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: Great. So, I think we’ve talked about what our next study might look like. When and if we actually mount that, we’ll, of course, be in touch since.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … you’ve got this in your wheelhouse now-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … this kind of idea. And I know you’ll be looking for more publications as you move-
Dr. Grant Franco: Yeah.
Dr. Bill Harris: … through your medical training-
Dr. Bill Harris: … advance your … Exactly.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: So, maybe we’ll wrap it up there, and thank you for going over this important new paper. And we’ll hope that the rest of the world has a chance to look at it, and think about it. That’s one of the troubles these days, there’s so much information you really don’t get any information sometimes.
Dr. Grant Franco: Yeah.
Dr. Bill Harris: And so, we’ll be promoting this. And for now, we’ll just wish the best in your career, your next step in training, and thank you for being with us on Omega Matters.
Dr. Grant Franco: Yeah. Thank you so much.
Dr. Bill Harris: Take care.
Dr. Grant Franco: Take care.
Dr. Bill Harris: Take care. Bye-bye.