Why You Need a Calcium Score to Know Your Real Heart Risk | Dr. Matthew Budoff & Mike Haney
In a recent episode of A Whole New Level, Levels editorial director Mike Haney sits down with Dr. Matthew Budoff, professor of medicine at UCLA and one of the world's leading experts in cardiovascular imaging and the prevention of heart disease. Budoff has spent more than three decades pioneering the use of coronary artery calcium scoring and CT angiography — and was a principal investigator on the landmark MESA study, which demonstrated that coronary calcium scanning outperforms nearly every other marker in predicting cardiac events.
The conversation covers why the coronary calcium score is so much more predictive than a standard cholesterol panel, how plaque actually forms and why it ruptures, what the difference is between calcified and soft plaque, how to build a smart diagnostic ladder from basic lipid tests through CT angiography, and what's on the horizon for treating LP(a) and inflammation as the next frontiers in cardiology.
If your calcium score is going up by 20% per year, that is not a benign process. That is not okay. That means that you're laying down new plaque.
— Dr. Matthew Budoff
The MESA study: what 25 years of data taught us about predicting heart disease
Mike Haney: All right. Well, Dr. Matthew Budoff, thanks so much for joining us today.
Matthew Budoff: Oh, it's a pleasure. Thanks for having me on.
Mike Haney: So, we could spend the entire hour here chatting about your CV — you've been at this for 30-plus years. But maybe by way of introduction, without going through everything, I wonder if you want to talk briefly about the MESA study and what it was and what you learned from it, and maybe what you're still learning from it with some of the data and how it's still being used.
Matthew Budoff: Yeah. So MESA was a Multi-Ethnic Study of Atherosclerosis. It was sponsored by the National Institutes of Health — 6,814 patients of Chinese, Hispanic, African-American, or white background, 50/50 men and women. So it was a really population-based study in the US, six sites around the country recruited, and it's been going on for now over 25 years. We started recruitment around the year 2000, so it's been a longitudinal assessment.
We first learned that coronary calcium is the best predictor of events of all the different markers we looked at. We looked at genetics, we looked at carotid plaque, we looked at ankle brachial and peripheral disease — nothing predicted events as well as a coronary calcium scan. And then we learned that things like aortic valve calcium adds a little value. We could see the bones and bone density — we can measure bone density from those CT scans accurately and we predicted hip fractures. So that same calcium score can give us aortic calcium and aortic valve calcium and bone density. But the coronary calcium is the big winner there, and that's what we're now using clinically to determine who needs treatment.
Mike Haney: And as I understand it, there's been a number of studies, dozens of studies, that have been done off of that data set. Are there any recent learnings off of the MESA data set that's moving things forward?
Matthew Budoff: Yeah. I think we learned that if you have a calcium score above 300 — so your total coronary calcium, the amount of plaque in your coronaries, is more than 300 — that that's equivalent to secondary risk. In other words, that you're at the same risk as somebody who's had a heart attack. So we're treating those patients a lot more aggressively.
We recently did a head-to-head study with the polygenic risk score. The polygenic risk score did not predict events with the calcium score in the model, but the calcium score did predict events if you put the polygenic risk score in the model. So it showed us that at least currently we're not ready for genetics to help us with heart disease — they just don't, it's not a robust measure yet. I think those are the most recent findings. But we're always learning. There are hundreds if not thousands of papers coming out from MESA over time.
Common misconceptions: plaque progression, healing, and what a rising score really means
Mike Haney: Well, we're going to come back and talk in a lot more detail about the CAC score. But just by way of maybe setting up why this is so important, I'm curious — a couple of questions as a sort of practicing cardiologist. What are some of the most common misconceptions that you find people you're talking to, the average lay people, still have about cardiac risk or cardiovascular disease? What are you often correcting?
Matthew Budoff: One that if you're — if the score is going up, that that may be from statins or from other therapies, and that that's not a bad thing, and then that you should ignore those changes. I think we learned from MESA and many other cohorts that if your calcium score is going up by 20% per year — so you have a score of 100 and now it's 125 a year later, or it's 200 a couple years later — that is not a benign process. That is not okay. That means that you're laying down new plaque, and the plaque is rupturing and healing and calcium is part of that process. But when you're laying down new plaque, that means that we have not stopped the process yet. So I think plaque progression is still a misconception of coronary calcium.
And some people think that since calcium represents some of the healing process, it's okay to have coronary calcium because that represents healing. But the only people who get healed are people who have had injuries. So your arteries have been injured, and when the artery gets injured, it could lead to a heart attack or stroke or death. So we don't want to see that process ongoing. We want to see quiescence — we want to see no plaque at all, a calcium score of zero, or we want to see a stable score over time.
How cholesterol becomes plaque: the physiology of atherosclerosis
Mike Haney: That's a good lead-in. I want to just do some sort of basic physiology because people hear a lot of these terms and I think are still kind of confused about what's actually going on in your arteries when we lead up to cardiovascular events. I think the terms people are going to be most familiar with are plaque and cholesterol. So what's the relationship between those? How does cholesterol floating through my blood — too high a cholesterol score — how does that become plaque?
Matthew Budoff: Yeah. So first and foremost, cholesterol is the most modifiable risk factor for sure. If you have high cholesterol and you have plaque and we reduce it, your event rate goes down. But cholesterol is not the only risk factor. So there are people with low cholesterol who have heart attacks, and there are people with very high cholesterol that never have heart attacks. So it's an important one, but it's not the only one. People get confused about that, I think.
But I think, you know, as we lower cholesterol, we can really impact event rates. And I think that's why we consider it the most modifiable of all the risk factors. And when you take somebody's cholesterol and you lower it dramatically, you can actually see regression of plaque. Not the calcium score — the calcium score won't go away, that's scar tissue. But you can stop the calcium score from going up, but more importantly, you can get rid of the non-calcified plaque that we can see on CT angiography or invasively — we can determine that your plaque is actually getting better and you have less plaque today than you had a year or two ago, which means regression, which is the goal of treatment, I believe.
Mike Haney: So if cholesterol — essentially your ApoB-containing particles — is embedding within your arterial walls, causing over time an inflammatory response, fibrous buildup, and you get plaque — if I've got the sort of college level or high school level physiology correct there — why can you get those situations where somebody has very low cholesterol but gets a plaque buildup, or vice versa? Where does that relationship break down if the physiology is causal in that way?
Matthew Budoff: Just the other factors. So let's say you had a really high — we're learning about LP(a). Let's say your LDL or your total cholesterol is low but your LP(a) is really high — that's another type of cholesterol that's not measured on the traditional panel. Then maybe we're just measuring the wrong type of cholesterol and you still have more plaque buildup. Or maybe it's your blood sugar — you have insulin resistance or diabetes or pre-diabetes and that's driving the plaque. Or blood pressure, or smoking. I mean, it's just — there are other risk factors that can change the association between cholesterol and plaque. But the building blocks of plaque are definitely cholesterol, and that's why it becomes one of the most important factors and the most modifiable to prevent not only plaque buildup, but when you treat cholesterol you can actually reduce events the most by treating cholesterol of all the interventions we can make.
The role of adipose tissue: why fat around the arteries drives inflammation
Mike Haney: And talk about the role of fat tissue or adipose tissue. I've heard about the sort of outside-in versus inside-out debate. Is the adipose tissue outside the heart affecting the plaque, or is the plaque affecting the adipose tissue? And I know you've got a pretty clear point of view on this. How does adipose tissue affect the plaque?
Matthew Budoff: Yeah. So I'm pretty confident — and I think most of us know, although except for one company that's purporting it may be the opposite — basically what we think happens is that inflammation, C-reactive protein, and interleukins, the inflammatory markers in our bloodstream, are produced in fat cells. So the adipocytes produce C-reactive protein and they release inflammation. If there's a lot of fat around the coronary arteries and that fat is metabolically active — in other words, it's excreting these biomarkers, this inflammation — that can affect the artery.
And the reason I think it's outside-in and not the other way around is that in arteries that do not have fat around them — for example, arteries that go into the muscle and they only have muscle around them — they never ever get atherosclerosis. So if it was inside-out, then the artery could still get atherosclerosis. There would just be no fat around it. But arteries that have no fat around them never ever ever get disease. So the fat has to cause the disease rather than the disease causing the fat to look different.
Mike Haney: So the presence of adipose tissue around the arteries or around the organ is a precursor — is a necessary factor for that plaque buildup to happen, because of that inflammatory response. Is that right? Or is there other places that that inflammatory response could come from and drive that plaque buildup even if your visceral fat was low?
Matthew Budoff: It's probably part of the process that drives the plaque or forms the plaque. And again, I've seen a hundred thousand of these angios now, maybe more. And when we see the arteries dive into the muscle, there's never been a case where there's even been a little speck of plaque. So I think that is what we would consider to be maybe a necessary co-actor — and that's how we can tie in inflammation, which we think is important and bad, into the heart disease process. That's how inflammation affects the arteries and propagates the plaque that's then laid down by the cholesterol and turns into calcification once it starts to heal.
Soft plaque, stenosis, and rupture: the two ways plaque becomes a heart attack
Mike Haney: I think the other thing that a lot of people are confused about when we talk about cardiac events is — I think blockage or stenosis, a buildup of plaque, is what people would most often associate with an event. But in fact soft plaque and rupture is also a risk factor — perhaps maybe a bigger risk factor. What's the relationship between soft plaque and a possible rupture versus stenosis versus it's just blocked and blood can't get through the artery?
Matthew Budoff: Yeah. So plaque can build up in the wall, but it doesn't block off the artery — the artery can stay open. For those of us that are not as healthy, or have so much plaque that the artery just can't stay open anymore, we start to get blockages. So it's the propagation of the plaque — a researcher named Glagov came up with his remodeling concept about 30 years ago. What he said was that once you hit about 40% of the artery filled with plaque, it can no longer outwardly remodel, and then it starts to block off the artery. But there are definitely some people who, even with minimal plaque, have their arteries blocked. And we have other people — like runners — who have a ton of plaque, but their arteries are open because they're doing a lot of exercise and keeping their arteries open through other physiologically healthy mechanisms.
Soft plaque just means that there's cholesterol only — there's no buildup yet of the calcification. It's usually an earlier plaque that hasn't had time to really develop into an atheroma and get into those stages of calcification. And we think that it's those earlier lesions that are more likely to rapidly grow, and eventually they can rupture. And if it ruptures, what happens is you release that fat and all of the other contents of the plaque that's sitting there into the bloodstream. And when the bloodstream sees that plaque, it starts to attract platelets. Platelets show up because the body thinks there's a hole in the artery, so it tries to plug the hole. But what it does is sometimes it plugs the entire artery. It over-responds — the platelets over-respond — you block the artery, and the patient has a heart attack or stroke. And that's the mechanism of heart attacks and strokes.
Mike Haney: So both are risk factors.
Matthew Budoff: For sure. Yeah. Both are risk factors. And that's why aspirin or other antiplatelet agents have been shown to be helpful for heart disease — because that's the platelet over-response, really, to a hole in the artery that causes the artery to get blocked off. And if the artery gets blocked off, no oxygen delivery to the tissue, and people die.
Building the diagnostic ladder: from lipid panels to calcium scores
Mike Haney: So I want to walk through kind of a diagnostic ladder of testing — the kinds of tests people might get for their cardiovascular health. And I think the most common is just your standard lipid panel. We talked a little bit about cholesterol's role in developing plaque, but also that there's a lot of variation. High cholesterol doesn't necessarily mean that you have high cardiovascular risk. How common is it that you see a high LDL — or let's say a high ApoB, if that's a more predictive marker — of dangerous cholesterol, but no plaque buildup? Is this a one-in-a-hundred-thousand unicorn, or is this 20% of the population walking around with high cholesterol but low plaque burden?
Matthew Budoff: Yeah. No, it might even be more than 20%. There was actually a study out of Sweden — Denmark — where they followed patients over time. Their average age was 62 years old, the average cholesterol was 193 milligrams per deciliter, which is very high, and 43% of those patients with very high LDL cholesterol had no plaque at all — not just by a calcium score, but by a CT angiogram. And we think that most of those patients were probably hereditary because there's a lot of heterozygous familial hypercholesterolemia in that region of Northern Europe, and they had no plaque at all. So I think it might be more common than you think to have just high cholesterol and no plaque — because maybe they don't have those other factors. Maybe they're not heavy, maybe they don't have diabetes or pre-diabetes, maybe they don't have the inflammation that's driving the disease. And maybe just high cholesterol by itself is not enough to cause a lot of plaque.
Mike Haney: And I know you've done studies, for instance, on the keto diet, which often has a characterization of very high cholesterol because of a lot of saturated fat or meat intake, and found not a real relationship. But you've also said: look, if you've got cholesterol in the 300s, particularly if it's going up, you should still be sort of watching this. So how do you think about the relationship, given that number of people who may not have that sort of direct relationship? How should people think about their cholesterol numbers? What gives them confidence that they are in one camp or another?
Matthew Budoff: The only way to know is to get a scan of the heart, I believe. I don't know if there's a better test right now. There's no better test right now, and I don't know if there will be. Hopefully — you never know with scientific development — but there's nothing that I'm aware of even on the early horizon that's better than either a calcium score or a CT angio of the coronaries.
And if your arteries are clean, the guidelines — the American College of Cardiology, the American Heart Association — say: if you have high cholesterol and you have no coronary calcium, your score is zero, you don't need to treat the cholesterol. You're not at risk in the short run. We're not talking about in your whole life, but for the next five years, you're off the hook for medications. But how do you know which side of the fence you're on? There's no way to know unless you look. So, of course, if you already have diabetes, if you already have heart disease, if you already have a lot of risk factors, then you should treat the cholesterol regardless because you're high risk. But if you're not, and you just have one lab value that's abnormal, I say we have to get a scan. If you're in the camp that has a lot of plaque, we treat aggressively. If you're in the camp that has no plaque, we use lifestyle changes and keep an eye on things, and five years later we'll do another test.
Mike Haney: And how do you think about the inverse — the folks that have low cholesterol, but for whatever reason decide to go get the scan and have some kind of plaque buildup?
Matthew Budoff: Yeah. So cholesterol is only one factor. And there was a paper called Interheart — they looked at how much of the risk of heart disease is attributable to all of these modifiable risk factors, and cholesterol was 50%. It was the biggest number — more than high blood pressure, more than diabetes, more than smoking, psychosocial factors, exercise — it was the most important. But it's only 50.
So if only 50% of your heart disease is explained by your cholesterol, then if you have other bad factors and your cholesterol is normal, you still have a 50/50 chance of developing heart disease with normal cholesterol. So cholesterol — and we see this all the time in the emergency department — we see patients coming in with heart attacks and they're like, I don't understand how I can have a heart attack, my cholesterol is low. And I'm like, well, but you have pre-diabetes and you have inflammation and you have high blood pressure and you have family history and genetics that are playing a role here. So you have heart disease, and it's not only cholesterol. We have to just separate out that cholesterol is the only factor that drives heart disease. It's the most important, it's the most modifiable, but it's not the only one.
Cholesterol is the most important, it's the most modifiable, but it's not the only factor. If only 50% of your heart disease is explained by your cholesterol, then if you have other bad factors and your cholesterol is normal, you still have a 50/50 chance of developing heart disease with normal cholesterol.
— Dr. Matthew Budoff
Advanced lipid testing and functional stress tests: where they fit in
Mike Haney: And how revealing are some of the more advanced lipid tests that you're now seeing out there? Some of these blood testing companies will sell you an oxidized LDL panel or give you 20 other apolipoproteins besides ApoB, or particle size — I think that's probably the one people hear about the most. Small and dense, that's bad; if you've got large fluffy LDL, don't worry about it. How do you think about the value of that advanced lipid testing?
Matthew Budoff: Yeah. So I am not using them routinely. There are some patients who really want more information and really want to dive into this. And I think they're reasonable tests. They're not widely accepted in our guidelines yet, they're not widely paid for, because we just haven't really proven exactly how to use that information in our day-to-day practice. I would say my lipidology friends who only live in the world of cholesterol would say that it informs them a lot about what's going on.
For me, I follow the patient over time, and if their plaque is getting worse — rapid progression on a calcium score, or their CT angio shows plaque is getting worse — then sometimes I do dive into those biomarkers to try to figure out where I am. ApoB, particle size, LP(a) — there's a bunch of additional cholesterol tests you can get. I mean, I love those — when you see all that information, I think it helps some people. But I think a lot of times your LDL is high, I'm treating your LDL, and I don't really care what the rest of that panel looks like.
Mike Haney: Yeah. I think that's useful. And the way we sometimes think about the value of these advanced tests is: is it actionable information? And if the action is going to be the same no matter what — because we need to treat it because we've seen some plaque in there — then how much is it actually useful? How about functional tests? I think that's kind of the next step a lot of people go through — you got a high LDL, the doctor puts you on the treadmill and has you run. Where do functional tests fit into this picture?
Matthew Budoff: Yeah. So functional tests are really falling off the map here in the world of cardiology. They're being pushed down in the guidelines to second and third tier testing, where for my whole career they were number one — now they're number two. We believe that anatomical information, plaque information, stenosis information is more important than functional information. Now there's definitely important information about how far people can exercise or what their exercise capacity is. But for most of us, we can derive that without putting them on a treadmill. We can derive that by just asking them the right questions — how far can you run, or how often do you run, or do you do Zumba, or do you get winded if you're in a Pilates class — and try to figure out where those people are physiologically.
But trying to discern who has coronary disease on a treadmill is really archaic and probably harmful. I would imagine down the road people will get sued for only getting a treadmill test on a patient, because treadmill has two problems. One, it only picks up really severe blockages — it only picks up 70% stenosis or more. So if you have a moderate blockage or even a mild blockage, it's going to be stone cold normal and it's going to give you the wrong answer. It's going to say, "Hey, you're doing well," and your arteries are filled with gunk. It's just not quite to that level. And even if you say, "Well, I really only care about 70% stenosis because that's where I can put my stent in and fix the artery," it only picks that up about two-thirds of the time. So it misses a full third of people, and it only tells you about the worst possible scenario.
So imagine now you're the President of the United States, you're healthy and you're running, and every year you get an executive physical and every year you get patted on the back for doing well because your exercise capacity is good and you passed your treadmill. After eight years you get out of office and your doctor says, you know what, you really need a calcium score — I know you've been having a little bit of unusual symptoms, let's just make sure your coronaries are okay. Your calcium score is over a thousand, and the next thing you know you get an angio because you have some symptoms, and you have three-vessel disease and get bypass surgery within months of your last treadmill.
And that was President Clinton. That's literally what happened. Eight treadmills, eight pats on the back by doctors reassuring him that he doesn't have heart disease, that his heart is great and he's healthy. And he used to run in DC — there are pictures of him running with the Secret Service. The treadmill missed it eight years in a row. And fortunately he got bypass surgery, because if he didn't, with the amount of disease he had, probably he would have had a big heart attack at some point, and unfortunately would have had a much worse functional life — or maybe, the heart attack in one-third of patients is life-ending. And we avoided all of that by getting the calcium score and then following that up.
Mike Haney: It's funny — when you mentioned the pictures of him running, I'm also remembering the pictures of him sitting in a McDonald's eating Big Macs. I feel like he was our first Big Mac president.
Matthew Budoff: I always joke that he ran, but he ran between McDonald's and Burger King. So yeah, it might have been a diet thing as well.
The CAC score: what it measures, what it costs, and who should get one
Mike Haney: Well, let's get into the CAC — the coronary artery calcium score. What is a patient's experience when your doctor says, "All right, we're going to get you a CAC score. What happens to me? What do I do?"
Matthew Budoff: Yeah. So you go in dressed as you are, you lay down on the table, you don't have to disrobe. There are no needles. They'll hook you up with just a couple of leads to your arms or to your chest just to track your heart rate. You'll take pictures — about 30 seconds later, they'll disconnect you and you're all done. No needles, no IVs, very simple test. And we take high-resolution images of the heart, slice it in very thin slices like a loaf of bread, to be able to see the artery at every level, and then we sum up how much calcified plaque you have in those coronary arteries.
Mike Haney: This test has been around for decades. You started working on this 30-some years ago, and I've heard you use the phrase "mammogram of the heart" — meaning, I took from that, the belief a long time ago was that this would be as common as mammograms have become over say the last 20 years as a diagnostic tool. And it has not been the case. Why is that? What happened over the last 30 years that this is still a relatively foreign test for a lot of people?
Matthew Budoff: Yeah. There's just no industry behind it. There was actually a very interesting documentary called Widowmaker — not the famous one about the mountaintop, but a documentary called the Widowmaker. And what they showed is: in 1989, a radiologist in San Francisco invented the calcium scanner, the CT scan that could do this. And in 1989, the coronary stent was invented — in San Francisco, a different radiologist, but born in the same city at the same time. Stents became a multi-billion dollar industry because it was driven by industry. Industry was helping promote it, helping propagate the science, helping propagate the benefits of it. And it became a big gorilla. Nobody did that for calcium scoring.
We had a group — we used to call ourselves the calcium club — there were five of us, five scientists that got together and talked about and tried to publish on the benefits of coronary calcium. So even if I lectured every day somewhere, I would hit dozens of doctors, not tens of thousands of doctors, to educate them. So I think without industry, the calcium score just kind of squandered and didn't grow, until the science came out — and that MESA study that we talked about was so important because it showed that calcium scoring is so predictive that our guidelines changed. And now we're seeing millions of calcium scores being done in the US per year. It's still not as popular as a mammogram, but we're certainly now in the millions rather than in the tens or hundreds of studies being done on an annual basis.
Mike Haney: And where does insurance fit into that? When did insurance — if it has — start covering this?
Matthew Budoff: Yeah. So insurance started paying after the 2018 guidelines. The cholesterol guidelines came out in 2018 — the American Heart Association, the American College of Cardiology said calcium scoring is useful for people who have intermediate risk. They have some risk factors, but they're not horrific. When that happened, Anthem Blue Cross — which is millions of Americans — United Healthcare, which is the biggest payer outside of Medicare, Blue Shield, started paying for calcium scoring in certain situations. Aetna pays for calcium scoring.
Now, many doctors will say it's not covered, or I'm not going to go through that process of getting prior authorization. So they'll just say, you know what, if it requires a prior authorization, I'll order the test but you're going to have to pay out of pocket, because I'm not going to fight the insurance company for you. Luckily, most places it's $99 around the country. Some places it's cheaper than that, some it's a little bit more, but somewhere between $99 and $129 is about fair market value. And I always tell people: look, it's the price of a good steak dinner. And if you want to have a lot more good steak dinners, you'll pay the one-time fee.
Medicare has not made a national coverage decision yet. So it's not a national policy by Medicare — that's the thing that's holding it back. And we're pushing, we're pressing Medicare to give it a national coverage decision, to say that it's a useful test. So when that happens, HMOs will have to cover it, PPOs will almost definitely cover it, and everybody will have access. We're halfway there.
It's the price of a good steak dinner. And if you want to have a lot more good steak dinners, you'll pay the one-time fee.
— Dr. Matthew Budoff
Mike Haney: How much is that a burden? The insurance coverage — I understand it can be a burden both in the pure financial sense, if it's not covered a lot of patients aren't going to pay for it, but also in what you just talked about in terms of how seriously doctors will take it. If there's a process that isn't insurance-covered, there can be an assumption that this is still fringe, this is not something that most people need to think about. How much of a barrier right now is just physician awareness — and being able to say to the patient, "Look, your insurance isn't going to cover it, but it's a $100 test, I highly recommend it" — versus getting over the hump of particularly the Medicare national coverage?
Matthew Budoff: Yeah. So we're really pressing. There are some very impressive physicians who have aligned themselves in the cardiology space to try to help pressure Medicare to get over the hump here and cover this test. We're not quite there yet, unfortunately. And I think now it is either: the doctor will say, I want you to get this test, I can make a phone call and it'll take five or seven or ten minutes — and they don't do it, usually their staff does. But some of them won't do that. They'll just say, you know what, if it requires a prior authorization, I'm not ordering it — you're going to have to pay out of pocket because I'm not going to fight the insurance company for you.
Mike Haney: And this is done at an imaging center typically, right? It's not typically going to be in your general practice physician's office.
Matthew Budoff: Yeah. You need a CT scanner, and that's not going to be at your smaller sites. So it could be in a big cardiology practice or a big medicine group that might own a CT scanner, but most of the time it's going to be either an outpatient imaging center or the hospital CT scanners.
Mike Haney: And do I need a physician to order it for me, or can I as a patient just walk in, like I can now do with some of this blood testing — Quest will just sell it to me if I want it?
Matthew Budoff: Yeah, some states allow you to just walk in. California, you're allowed to just walk in and get it done — it's considered a screening test, and you can get screening tests without a prescription. In some states you need a doctor's order. So it's just a mix. And sometimes the doctor who works at that center will — you fill out a quick questionnaire and they say, "You qualify, I'll order the test for you." So sometimes you can get it ordered from the imaging center themselves. They are usually MDs or DOs working at that imaging center, so they have the ability to order the test if they so choose.
Mike Haney: And how important is it, if I go rogue and sort of just go get it on my own in that way, to have a physician to go over the results with? Again, my analogy is blood testing — a lot of people are getting expanded blood testing, and one of the things we're often telling folks is, if you have some outlying markers, you really need to talk to a professional about this and don't just go on ChatGPT and try to interpret it yourself. Is the CAC a little bit more clear — if I just see a CAC of 600 and I have high cholesterol, I can go, okay, I have a problem here — or if my CAC is zero, can I just walk away? Or do I really need to go over those results with a doctor I trust?
Matthew Budoff: I always advocate for any test that you have somebody you can talk to about the test and put it in clinical context for you. But if you're over the age of 40 and you have a score of zero, that's a pretty good sign and there's not much the doctor should have to say about that. So I will say that would be the exception.
And if you're young and have plaque — any amount of plaque — because we also not only give you a total score, but we say what's your age-adjusted percentile, how are you relative to other people your age. A 36-year-old female with a score of one — one's not a big number, except that she's in the 99th percentile for 36-year-old women, because 36-year-old women should not have a score of one. And she had a non-invasive angio as part of the testing and she had some plaque in her arteries. So she's way ahead of the curve, and one is not a good number because she's 36. If she was 76, a score of one would be celebration time — go out, have a drink, you're fine, you're not going to have a heart attack. So you have to have it in some clinical context.
Mike Haney: And I would imagine, given what we just talked about, you also want to — whatever the score is — look at that suite of co-actors: both cholesterol, but also things like insulin resistance, maybe any kind of advanced lipid testing like an LP(a). If you get that done even once, you know what your LP(a) is essentially.
Matthew Budoff: No, absolutely. It's always in context. But again, zero is generally a pretty good number unless you're young. Young people — calcium may not have yet been part of the process and you want to be a little careful. If you're 18 or 20, I don't care if your mom or dad had heart disease — you're too young to get a calcium score. We usually say you have to be at least 35 to 40 to even go for that test.
Who should get a scan, and at what age
Mike Haney: Why is that? Why would you not look in even younger people, particularly if they have a family history?
Matthew Budoff: Yeah, the yield is too low — the number of people who have plaque is very low. But we also think that the earliest stages of plaque is what we talked about a little earlier — soft plaque, non-calcified plaque. And if you have non-calcified plaque or soft plaque, your calcium score is going to be zero. That happens more frequently in younger people, where they only have soft plaque initially and they haven't yet calcified the plaque. So we don't want them to get falsely reassured and say, "Your calcium score is zero, you don't have any plaque" — which is true when you're older. If you're older and your score is zero, chances are you have no plaque at all in your coronaries. But if you're younger, you might have soft plaque that hasn't yet calcified, and you might have caught the process a little too early.
Mike Haney: Yeah. So let's talk about that — given what we discussed before about the role of calcified plaque leading eventually to stenosis versus soft plaque leading potentially to rupture, and how that can still be a risk factor — the CAC is only measuring that calcified, hardened plaque, which some might call healed. It's not going to rupture. Why is it so predictive of coronary events down the road? Is it just that it's such a good proxy — if you've got any at all, then we just know that you are prone to forming plaques from whatever factor is driving it?
Matthew Budoff: Yeah. I mean, I always refer to it as what's called the tip of the iceberg. An investigator named John Rumberger — he used to be at Mayo, he's now in Columbus, Ohio — came up with this concept that calcium is the tip of the iceberg. Just like the Titanic goes downstream and sees an iceberg — it didn't say, "Let's send divers below the surface to see if there's something that can tear a hole." It knew that 85% of the iceberg is below the surface of the water. The same is true with coronary calcium. If you have coronary calcium and you can see it, that means you have a lot of soft plaque and non-calcified plaque below the surface of the water. So it really is just a marker of the overall process. The higher the calcium score, the more overall plaque you have. The lower the calcium score, the less plaque you have. And if your score is zero, you either have nominal or no plaque at all.
Calcium is the tip of the iceberg. If you have calcified plaque and you can see it, that means you have a lot of soft plaque and non-calcified plaque below the surface of the water.
— Dr. Matthew Budoff
CT angiography: the next rung on the ladder
Mike Haney: That's a good lead-in to what I think is the next sort of rung on the ladder, which is the CT angiogram. So what is that telling me that's different from the CAC score?
Matthew Budoff: Yeah. So the CT angiogram is almost a natural evolution of the calcium score. The calcium score: EKG leads, lay on the table, no needles, no IV, and you get an answer. With the CT angio, it's almost the exact same test except we're putting dye in the arm — contrast, intravenous dye — into the blood vessel to fill the artery with dye, just like we would for an invasive angio. So now we can see how big the artery is, whether there's a blockage, and we can see all the soft plaque because the dye lights up the soft plaque. And now we can not only see the tip of the iceberg, but we have underwater vision and we can see the entire iceberg.
Mike Haney: And why, given that that's giving me so much more information, wouldn't I just jump to that? What's the reason to start with a CAC?
Matthew Budoff: Well, if your CAC is zero and you're over the age of 40 for men or 50 for women, and your score is zero, the chance of the CT angio showing you anything is low. And dye can cause some kidney problems in rare cases, it can cause allergies. In my career, unfortunately, we had one person who had a severe dye allergy and passed away. It's about one in a hundred thousand — the number we quote — but it finally happened to me last year after 30 years of imaging. So there's a small, very very small, but real risk of giving dye. And then the cost is more — the average cost of a CT angio is about $600 or $800. Stanford charges $15,000 for a CT angio if you walk in and say you want to get the better test. So there's a cost, there's a minuscule risk. I would say start with the calcium score in most cases, and then progress to the CT angio if you need it. But some of my colleagues would say, why not just get the Cadillac up front and get the best test you can get and know the answer? And a lot of patients do that — they come in and they get both.
Mike Haney: So what are the conditions under which you would advance somebody from a CAC to a CT angio?
Matthew Budoff: If they're too young for a calcium score, I would think about a CT angiogram instead — because a calcium score may be unreliable because they're too young.
Mike Haney: Is that just to understand why a young person would even be visiting you — is that because they're symptomatic or because they have a family history?
Matthew Budoff: No. I mean, we're getting these LP(a) tests and patients have sky-high LP(a), and I don't know if they have heart disease or not. Not everybody who has a high LP(a) gets heart disease, just like not everybody with high cholesterol gets heart disease. So if they have familial hyperlipidemia, or if they have a high LP(a) or a bad family history, or symptoms at a younger age, then I think a CT angio is the right first test to do.
If they're older and their score is zero, I've obviated the risk in at least 95% if not 99% of those patients with a simple calcium score. So for me, that's enough to say your score is zero or two — don't worry too much about it. But if they have a high score, high for their age or high in general, they might have blockages, they might have an inordinate amount of soft plaque — that's when I also start thinking about a CT angiogram to get more information. So zeros in young people, or anyone else who has a disproportionately high score — I'll often progress them to a CT angiogram.
Mike Haney: And a disproportionately high score — I know it varies by age — but are we talking 500, or is it 100-plus? Where do you start to think we need to look further?
Matthew Budoff: A score of 100 is a high score to me. I think that's high risk in the guidelines. If they're truly asymptomatic, they're exercising, they feel great, and they have a score of 125, I just put them on a cholesterol pill and treat their underlying risk factors and keep an eye on them. If they have some questionable symptom — "I do get a little bit of something funny when I'm running, I get some shortness of breath I can't fully explain" — I have a low threshold to progress them to a CT angiogram once their score is above 100.
Full-body MRI: hype, false positives, and what it misses
Mike Haney: Well, the other last test I want to talk about — because again it's one that's being pushed a lot direct-to-consumer — is the MRI, the full-body MRI or a cardiac MRI. Where do you stand on the utility of an MRI?
Matthew Budoff: So we've been there and done that 20 years ago. In 1997, the front page of Time magazine — Oprah got a full-body CT scan, head to toe. They colorized her organs, made it look very nice. It was literally a color image of theoretically her organs on the cover of Time magazine. We were doing those full-body scans with CT for 20 years, and they kind of went out of favor because there are so many false positives. So many patients have a little funny-looking nodule, or women had their uteruses removed only to find out they had fibroids because on a CT we can't totally differentiate what's tumor versus not. Same thing with MRI — it's revisiting this exact same thing, what we call the body scan. We still have some people who do it with CT and with MRI. You're looking for early cancer, you're looking for other pathology, but the false positives far outweigh the true positives. And a lot of people go down a rabbit hole of getting multiple tests — a liver ultrasound, then a uterine ultrasound, then a follow-up PET scan or another CT scan — and they get all this testing only to be told, oh yeah, that was all fine, you're okay.
So I'm not a huge advocate of it. But some people are very anxious about cancer, and certainly there are some cancers, like pancreatic cancer, that we find too late. And I think there are some places where screening is helpful. For lung cancer, you need a CT scan, not a full-body MRI. And the problem with MRI is you can't see the coronaries — the arteries on the heart don't show up. So the number one cause of death is completely missed. So if you are going to get a full-body MRI, also get a calcium score.
AI-assisted imaging: how tools like Cleerly are changing plaque analysis
Mike Haney: And maybe before we leave testing, talk about Cleerly and the role of AI analysis of these results, because my understanding is that's moved things forward quite a bit.
Matthew Budoff: Yeah. So Cleerly is probably the leader — the first AI software that's come to the public to take those CT angio images and really evaluate them in a much more comprehensive way, using computing power to say: you have 32 millimeters of soft plaque, of that soft plaque 6 millimeters is really bad early plaque, and you have 150 millimeters of calcium, but some of that is really stable calcium and some of that is not so stable calcium. So they give you a much better differentiation than I can do with my eye — how much plaque you have in millimeters cubed, and which type of plaque it is: is it vulnerable plaque, is it soft plaque, is it calcified plaque, is it stable calcified plaque?
Regression vs. stabilization: how aggressively lowering LDL can turn things around
Mike Haney: So let's talk about — I've gone ahead and gotten these tests, I've got results, I've got some plaque buildup. Now what do I do? Am I mostly looking to stabilize, or can I actually regress some of that plaque buildup?
Matthew Budoff: Yeah. And we absolutely can see regression. I saw a case this morning — a woman who was very aggressively treated. She had a moderate blockage in her left anterior descending, what we call the widowmaker, and she now has a mild blockage there. We know for sure you can see regression. We don't have liquid Drano — we're not going to get rid of all of the plaque in the arteries and have clean coronaries someday — but we can get better.
The best method that we know of right now is getting that LDL cholesterol super low — below 55 milligrams per deciliter — where we start seeing regression of plaque. And that's been seen on multiple imaging studies over the last two decades.
Mike Haney: And that's interesting. Maybe we'll just do a quick kind of stack ranking — of diet changes, which I think when we think about cholesterol, most people are going to go to saturated fat, maybe increased fiber. Then we've got statins and what they do. I know you've spent a lot of time studying various supplements — garlic and things like that. We've got the role of supplements, red yeast rice people might hear about. And then exercise, sleep, stress, all of the other lifestyle stuff. If our goal is either stabilization or even regression, how do you kind of stack rank those interventions? If I don't have any ideological commitment to any of those, I just want to get better.
Matthew Budoff: So it's lower LDL, however you get there. The best two ways that we know of — the most potent ways of all the things you mentioned — is either the statins, or there are PCSK9 inhibitors, the injectables. Those will get your LDL low. And both of them have proof that we can see regression if we get the LDL low with either a statin and/or these PCSK9 injectables to lower cholesterol. There is an oral PCSK9 on the near horizon — I believe maybe another year out. So for people who don't like to inject themselves, there will be another option, and it's not a statin. So all the negative things about statins, PCSK9s don't have those issues that some people perceive statins to have.
Mike Haney: And when we talk about that regression via bringing LDL down, are we talking about the calcified plaque or the soft plaque or both?
Matthew Budoff: So the calcified plaque will not ever go down. Calcified plaque is scar tissue. It can stop going up dramatically, but it may go up a tiny bit as you convert the soft plaque to calcified plaque. But it's the soft plaque that goes down, and the stenosis can actually go down a little bit as well. You can go from a moderate blockage to a less-than-50% blockage with aggressive medical therapy. The best data we have right now is that it's the LDL as the target.
Mike Haney: And that's because that blockage is going down because I'm getting rid of that soft plaque — because whatever's built up in terms of that calcified plaque, as you say, that's just going to stay there.
Matthew Budoff: Exactly. Exactly.
Mike Haney: And given that what we're really reducing is the soft plaque — am I going to see that progress? I've done all these things and now it's two or three years later. I want to see that I'm progressing. Is a CAC score going to tell me that, or do I need to go to a CT angio at that point to see my lessened burden of plaque?
Matthew Budoff: Yes. If you really want to see the plaque burden, you not only need to do the CT angio, but you probably need to have the additional analysis. Cleerly is just an analysis of the plaque, but you probably need that additional Cleerly analysis to really see the plaque volumes go down. Because I can eyeball it and say it looks a little bit better, but they can give you millimeters cubed at baseline, millimeters cubed at follow-up, and if the follow-up number is lower, that's regression for sure.
Mike Haney: And what kind of follow-up schedule do you like when you put somebody on a treatment plan?
Matthew Budoff: Yeah. So a colleague of mine who I respect a lot — he was one of our former past presidents of the Society for Cardiovascular Imaging for CT — said the numbers are one, two, three, or four. So if you have a lot of plaque and you're being very aggressive, you can see changes as early as one year. If you want to be more moderate — you only have some plaque — it's going to take a little longer to show changes, so you wait two years. If you have minimal plaque, you have to wait a while because the error of the test at the very low end may be significant — you wait three years. And if you have no plaque at all, you can wait at least four years before you take another test.
What's next: LP(a) drugs and anti-inflammatory treatments on the horizon
Mike Haney: All right. So maybe where we'll leave it here — because we're just about at the hour — is what's coming. You're still actively studying all this stuff. What are you excited about that's on the horizon?
Matthew Budoff: Yes. So literally the Horizon trial is very exciting — it's pelacarsen, it's the LP(a)-lowering drug. We'll know next March if it worked and how well it worked. Can we modify this LP(a), and then what is the effect on the coronaries? We have two studies ongoing now using coronary CT angio to look at the effect. So I think the LP(a) story is the next to unfold.
After that it's going to be inflammation. Does treating inflammation really lower your event rates? And we have some data — I did work with colchicine, which is a more indirect anti-inflammatory agent — but we're doing studies now with direct anti-inflammatory agents that really stop those interleukins directly, and whether we can reverse or slow heart disease with those agents. And that'll be the next answer. So it's LP(a) and then inflammation as the next two parts of our story to unfold in cardiology.
Mike Haney: Excellent. Well, thanks so much for all of this today. I think our takeaway is: let's get more CAC tests out there, let's have more people go ask for this or get it from their doctor.
Matthew Budoff: Absolutely. And thank you so much for having me on — and spread the word a little bit wider.
This article is based on a conversation with Dr. Matthew Budoff, a professor of medicine at UCLA and one of the lead investigators on the Multi-Ethnic Study of Atherosclerosis (MESA), a landmark 25-year NIH-funded cardiovascular study.