Latest / What's Your Problem? / The New Science of Preventing Heart Attacks

Transcript

The New Science of Preventing Heart Attacks · What's Your Problem?

• 0:15
  Speaker 1: Pushkin.
• 0:20
  Speaker 2: The story of heart attacks used to be a story
• 0:22
  Speaker 2: basically about plumbing. You know, the arteries that feed the
• 0:26
  Speaker 2: heart with blood are like pipes, and over time and
• 0:29
  Speaker 2: some people, fatty plaque builds up on the inside of
• 0:33
  Speaker 2: those arteries, like gunk on the inside of a pipe.
• 0:36
  Speaker 2: And as the plaque builds up more and more, the
• 0:39
  Speaker 2: space where blood can flow through the artery gets narrower
• 0:43
  Speaker 2: and narrower, and eventually a blood clot blocks that narrow
• 0:48
  Speaker 2: artery all together. That's heart attack. And so a key
• 0:51
  Speaker 2: thing that doctors looked at when they were trying to
• 0:54
  Speaker 2: prevent heart attacks was how much narrowing is there, how
• 0:58
  Speaker 2: clogged is the pipe? Over time, though, doctors noticed a
• 1:02
  Speaker 2: surprising pattern. Lots of people were having heart attacks even
• 1:07
  Speaker 2: when they didn't have a ton of plats build up,
• 1:10
  Speaker 2: even when their pipes weren't particularly clogged to begin with.
• 1:13
  Speaker 2: It took a while to figure out what was going on,
• 1:16
  Speaker 2: and it's taken even longer to figure out what to
• 1:18
  Speaker 2: do about it. Heart disease is still the biggest killer
• 1:21
  Speaker 2: in the world, but in the past few years a
• 1:25
  Speaker 2: bunch of new technologies have come together, and it seems
• 1:28
  Speaker 2: like a new, better approach to preventing heart attacks may
• 1:32
  Speaker 2: be here very soon. I'm Jamie Goldstein and this is
• 1:42
  Speaker 2: What's Your Problem, the show where I talk to people
• 1:44
  Speaker 2: who are trying to make technological progress. My guest today
• 1:47
  Speaker 2: is Eric Topel. He's a cardiologist and the founder of
• 1:51
  Speaker 2: the Script's Research Translational Institute in San Diego. He's also
• 1:56
  Speaker 2: one of the most cited medical researchers in the world.
• 1:59
  Speaker 2: His problem is this, how can doctors do a better
• 2:03
  Speaker 2: job at preventing heart attacks. Topel was early to this
• 2:07
  Speaker 2: shift in thinking about heart age, this shift away from
• 2:11
  Speaker 2: the plumbing model. The new model, he told me, focus
• 2:14
  Speaker 2: is not on how much plaque has built up in
• 2:17
  Speaker 2: the arteries around the heart, but on what's going on
• 2:20
  Speaker 2: with the plaque that's there, because even a small amount
• 2:24
  Speaker 2: of plaque can put patients at high risk of a
• 2:26
  Speaker 2: heart attack if that plaque is inflamed and unstable and
• 2:30
  Speaker 2: likely to rupture. He recently wrote an essay about this
• 2:33
  Speaker 2: shift and about the emerging screenings and interventions that could
• 2:38
  Speaker 2: lead to fewer heart attacks. To start, we talked about
• 2:42
  Speaker 2: how doctors figure out who is at high risk in
• 2:44
  Speaker 2: the first place. Topel is particularly optimistic about a new
• 2:48
  Speaker 2: approach that combines a CT scan of the arteries around
• 2:52
  Speaker 2: the heart with an AI model that detects inflammation in
• 2:56
  Speaker 2: those arteries. And he told me about one recent study
• 2:59
  Speaker 2: in the United Kingdom that used that approach.
• 3:02
  Speaker 3: The results were pretty striking. Forty thousand consecutive people in
• 3:06
  Speaker 3: the UK they use this tech and they found that
• 3:10
  Speaker 3: people with inflamed arteries with no narring had a very
• 3:14
  Speaker 3: high risk of heart attack and death. And so now
• 3:19
  Speaker 3: we have a way without an invasive technology to map
• 3:23
  Speaker 3: out a person's arteries, which is exciting, and that is
• 3:28
  Speaker 3: you know, if you had all three arteries of flame,
• 3:30
  Speaker 3: the risk ratio for having a heart attack over the
• 3:32
  Speaker 3: next years is like thirty fold, I mean huge increase.
• 3:36
  Speaker 3: If one artery inflamed is still important. So we have
• 3:38
  Speaker 3: now moved in the whole dogma of cardiology from blockages
• 3:45
  Speaker 3: to inflammation.
• 3:47
  Speaker 2: And so there are several companies right that are doing
• 3:52
  Speaker 2: this now, that are doing CT scans of the heart
• 3:55
  Speaker 2: plus AI to assess somebody's risk of having a heart attack.
• 3:59
  Speaker 2: Just talk me through those companies kind of what they
• 4:01
  Speaker 2: figured out, what they're offering, like what's beenef to approved,
• 4:04
  Speaker 2: what's covered by insurance if you know that, Like what's
• 4:06
  Speaker 2: going on with that?
• 4:07
  Speaker 3: Yeah, there's four of them now and they use different
• 4:11
  Speaker 3: technology with AI, so you know, the one that is
• 4:18
  Speaker 3: soon to be approved by FDA is a University of
• 4:20
  Speaker 3: Oxford spin out from the UK. It's called Karista, and
• 4:24
  Speaker 3: it's the one that really directly uses AI to gauge inflammation,
• 4:28
  Speaker 3: like I described, with the big data sets of the
• 4:31
  Speaker 3: forty thousand people and the outcomes.
• 4:35
  Speaker 2: I mean, I will say when you're just for me
• 4:38
  Speaker 2: knowing essentially nothing about the specifics of this case and
• 4:41
  Speaker 2: knowing a little bit about aim more generally, like there's
• 4:44
  Speaker 2: some level where what you really want is just the
• 4:47
  Speaker 2: biggest data set you can get and of coronary CT
• 4:52
  Speaker 2: scans and clinical outcomes and then just throw it at
• 4:56
  Speaker 2: the AI and say you figure it out.
• 4:58
  Speaker 3: Yeah, well that's basically what Charista, or well, Universe of
• 5:02
  Speaker 3: Oxford then they had a spin out company.
• 5:04
  Speaker 1: That's what they did.
• 5:05
  Speaker 3: So you're absolutely right, you want basically auto d idactic
• 5:09
  Speaker 3: to let the data see for itself.
• 5:11
  Speaker 1: It don't have any biases.
• 5:13
  Speaker 2: Like like the AI that beat go you know, like
• 5:16
  Speaker 2: they try and teach it the rules. They just said,
• 5:19
  Speaker 2: go play a billion games ago and figure it out
• 5:21
  Speaker 2: and it did right exactly. So you're saying the FDA
• 5:28
  Speaker 2: is likely to approve this test soon. Oh yeah, So
• 5:32
  Speaker 2: say the FDA approves this, like there's some universe of
• 5:36
  Speaker 2: people who maybe they haven't had a heart attack, but
• 5:39
  Speaker 2: they know they're at high risk for the classic reasons, right,
• 5:43
  Speaker 2: or they think they may be at high risk, and
• 5:45
  Speaker 2: this can give them a better sense, assuming that insurance
• 5:51
  Speaker 2: will pay for it, or people have had a pucket.
• 5:53
  Speaker 2: What do you do about it? What if I go
• 5:55
  Speaker 2: get this test and it says you're at high risk,
• 5:57
  Speaker 2: like I'm already taking a stat and I already exercise,
• 5:59
  Speaker 2: I don't smoke. What does it mean?
• 6:02
  Speaker 1: There's always more you can do? Right?
• 6:04
  Speaker 3: Well, So first, okay, firstly, on the LDL story, we
• 6:08
  Speaker 3: can get that down to very low levels. Yeah, and
• 6:11
  Speaker 3: that will help, you know, getting it down well below
• 6:13
  Speaker 3: to thirty twenty, you know. Okay, So we have so
• 6:17
  Speaker 3: many tools to do that.
• 6:19
  Speaker 2: So LDL is bad cholesterol basically and typically right, typically
• 6:25
  Speaker 2: the guideline is you wanted under one hundred. But you're
• 6:27
  Speaker 2: telling me, if a patient is at high risk, it's
• 6:30
  Speaker 2: good to get it much lower than that.
• 6:32
  Speaker 3: If your ct says you've got three inflamed guarteries. I
• 6:35
  Speaker 3: wanted to get your LDL down to you know, twenty
• 6:39
  Speaker 3: or ten. Yeah, okay now, and we have the way
• 6:41
  Speaker 3: to do that in almost everyone.
• 6:43
  Speaker 1: But that's just the beginning.
• 6:45
  Speaker 3: Then we check your LP LITTLEA because a lot of
• 6:49
  Speaker 3: people they're ldl's okay, but their LP little A lipoprotein
• 6:52
  Speaker 3: A is high.
• 6:53
  Speaker 1: And later this year we're going to have drugs to.
• 6:56
  Speaker 3: Treat that we've never had that before, okay, And that's
• 6:59
  Speaker 3: a high proportion of people that have that risk factor.
• 7:02
  Speaker 3: We would measure inflammation in your blood with things like
• 7:07
  Speaker 3: high sensitivity c P and cytostat and other emerging markers,
• 7:12
  Speaker 3: and we could use that to say, oh, well, we're
• 7:14
  Speaker 3: bringing it down and that's really good.
• 7:16
  Speaker 2: Let's just talk about inflammation for a seconds. That's where
• 7:19
  Speaker 2: we are, and like people have some kind of sense
• 7:21
  Speaker 2: of what inflammation is, but also not right.
• 7:26
  Speaker 3: So what is inflammation, Well, inflammation is a response to.
• 7:34
  Speaker 1: Injury.
• 7:37
  Speaker 3: You know, we've been talking about in the artery, so
• 7:39
  Speaker 3: it can use that. So let's say you're a smoke
• 7:42
  Speaker 3: or you have high blood pressure, your diabetes, you may
• 7:46
  Speaker 3: have some injury of the lining of your artery, and
• 7:51
  Speaker 3: the immune system comes along and picks that up because
• 7:54
  Speaker 3: it's trying to to seal it out, to heal it.
• 7:58
  Speaker 3: But unfortunately it backfires because cells from the immune system
• 8:04
  Speaker 3: get into the artery where there's been some injury, and
• 8:07
  Speaker 3: those cells have a mind their own and they produce
• 8:12
  Speaker 3: so called cytokines chemokind. These are proteins that then bring
• 8:17
  Speaker 3: in more self and it sets up a vicious cycle
• 8:20
  Speaker 3: of inflammation. So inflammation stems from the immune system. Of
• 8:26
  Speaker 3: those are white cells that include lymphocytes macrophages. But the
• 8:31
  Speaker 3: problem is that they can unleash inflammation. So it's part
• 8:36
  Speaker 3: of our healing inflammation is it can be a healing
• 8:40
  Speaker 3: response and it can be an untoward injury disease causing response.
• 8:45
  Speaker 2: Yeah, and when you get the disease causing response, say
• 8:48
  Speaker 2: in the arteries, like what is the what is the
• 8:51
  Speaker 2: sort of mechanism? Why is it? So I get that
• 8:54
  Speaker 2: there is some injury to the artery and the immune
• 8:56
  Speaker 2: system responds and that's like so far, so good. Yeah,
• 8:59
  Speaker 2: And if everything goes well, it fixes it and then
• 9:01
  Speaker 2: it's done and the artery goes on as morral. But
• 9:04
  Speaker 2: sometimes that doesn't happen, and you have the unhappy inflammation
• 9:07
  Speaker 2: story where it keeps feeding on itself and instead of
• 9:09
  Speaker 2: leaving well enough alone, it just keeps being inflamed. What
• 9:13
  Speaker 2: happens then? Why is that bad? Why does that cause
• 9:16
  Speaker 2: a heart attack? Eventually?
• 9:17
  Speaker 3: Oh? Well, I mean the common thread here is the
• 9:20
  Speaker 3: heart attack is a rupture. It's like a burst, you know.
• 9:24
  Speaker 3: Finally the artery is hot. It's just accumulating more of
• 9:30
  Speaker 3: this inflamed constituents and it just eventually it just leads
• 9:36
  Speaker 3: to that lining so called endothelium. It splits and then
• 9:42
  Speaker 3: the body says that, oh, we better go here and
• 9:45
  Speaker 3: clot that to seal it up, and unfortunately that clot
• 9:49
  Speaker 3: can cut off the BUTD supply and cause a heart attack.
• 9:52
  Speaker 3: And by the way, that inflammation and arteries is probably
• 9:57
  Speaker 3: that response. There's unquestionably there's some genetic story going on there. Okay,
• 10:04
  Speaker 3: So that why would some people be exubert inflammation response
• 10:09
  Speaker 3: whereas others you know that they don't really.
• 10:13
  Speaker 1: Get into that.
• 10:14
  Speaker 3: And so the point being is we have new drugs
• 10:18
  Speaker 3: and ways besides lifestyle, which you know, seventy five percent
• 10:22
  Speaker 3: of Americans don't even have the basal minimum exercise, physical activity.
• 10:27
  Speaker 1: Right, so you know there's.
• 10:29
  Speaker 3: Things things like sleep. Sleep health influences your body level
• 10:34
  Speaker 3: of inflammation. By the way, we have these clocks now,
• 10:38
  Speaker 3: artery clock, heart clock, immune system clock. These are collection
• 10:43
  Speaker 3: of proteins from your blood, from your plasma. They can
• 10:46
  Speaker 3: tell us if your artery arteries are aging faster than
• 10:50
  Speaker 3: the other organs in your body. That would be a
• 10:52
  Speaker 3: real tip off that something's not good here. So we
• 10:55
  Speaker 3: could find we could find the high risk people. We
• 10:58
  Speaker 3: can use not only find it, but then when you
• 11:00
  Speaker 3: can use these various blood tests to say, are we
• 11:04
  Speaker 3: making headway now that we got your sleep better, and
• 11:08
  Speaker 3: we got your exercise more and we have you on
• 11:10
  Speaker 3: a much better healthier diet. We got your LDL down
• 11:13
  Speaker 3: to twenty, what's your artery clock doing, what are your
• 11:17
  Speaker 3: inflammation markers doing, what's your immune system look like?
• 11:20
  Speaker 1: Now? We never had this stuff before. That's what's so extraordinary.
• 11:24
  Speaker 2: And everything you're talking about is available now. You're not
• 11:28
  Speaker 2: talking about what will be available.
• 11:30
  Speaker 3: Everything I've talked about except the LPA drugs which are
• 11:33
  Speaker 3: later this year, and also the multimodal AI packages that
• 11:39
  Speaker 3: take all your data. You're electronic health threat get your exposures,
• 11:42
  Speaker 3: your genetics, your proteins markers. That is, no doctor can
• 11:48
  Speaker 3: basically do this analysis in their head or even if
• 11:51
  Speaker 3: you if you lock them up in an office.
• 11:54
  Speaker 1: They couldn't do the analys You need help.
• 11:56
  Speaker 3: So this is another way AI kicks in. And then
• 11:59
  Speaker 3: there's other things like, for example, your retina. Did you
• 12:03
  Speaker 3: know your retina picture is incredible gateway to your risk.
• 12:07
  Speaker 1: For heart disease?
• 12:09
  Speaker 2: I didn't know it until I read your essay. We're discussing, Yes, it's.
• 12:13
  Speaker 3: A remarkable and we're not using you and someday we'll
• 12:16
  Speaker 3: be taking the selfies of our retina and getting AI
• 12:19
  Speaker 3: interpretation of that. The key here is identifying who is
• 12:23
  Speaker 3: the vulnerable patient and then getting all over that all
• 12:27
  Speaker 3: the ways we know.
• 12:28
  Speaker 2: So here is an interesting coincidence. My father lived in
• 12:35
  Speaker 2: San Diego for a long time, and one time I
• 12:37
  Speaker 2: was visiting him there and he happened to be going
• 12:39
  Speaker 2: to visit his cardiologist at Scripts where you work. His
• 12:43
  Speaker 2: name was Evan Muse, and I was just chatting. I
• 12:48
  Speaker 2: was sitting in the exam room chatting with the doctor
• 12:50
  Speaker 2: and he mentioned that he was running this was an
• 12:53
  Speaker 2: experimental project at the time to assess your genetic risk
• 12:58
  Speaker 2: for heart attack, and essentially every man in my family forever,
• 13:03
  Speaker 2: as far as I know, has had a heart attack,
• 13:05
  Speaker 2: many of them relatively hung. So I said I should
• 13:07
  Speaker 2: do that, and I took the test, and unsurprisingly, I
• 13:10
  Speaker 2: have an extremely high genetic risk for heart attack. So
• 13:14
  Speaker 2: I started taking a statin. It's basically the end of
• 13:16
  Speaker 2: that story. So anyways, I'm glad that I learned about
• 13:20
  Speaker 2: that test. It still seems pretty, at least at that time,
• 13:23
  Speaker 2: kind of fringy. My primary care doctor didn't tell me
• 13:26
  Speaker 2: about it, Like what's happening with genetic tests for heart
• 13:30
  Speaker 2: attack risk?
• 13:32
  Speaker 1: I'm so glad you're asked me about that.
• 13:34
  Speaker 3: By the way, Evan Muse and I share offices at
• 13:37
  Speaker 3: Scripts Clinic. I trained Evan as a cardiologist and really
• 13:41
  Speaker 3: proud of him. Now, polygenic risk scores should be universal.
• 13:47
  Speaker 3: They're very low cost, they're very accurate now to help
• 13:52
  Speaker 3: gauge risks, as they did in you. So you are
• 13:55
  Speaker 3: a vulnerable patient.
• 13:57
  Speaker 1: Now.
• 13:57
  Speaker 3: The difference polygenic risk is this is now looking at
• 14:01
  Speaker 3: hundreds of gene variants that collectively, even if you know
• 14:06
  Speaker 3: what's really important is you knew it from your family tree.
• 14:09
  Speaker 3: But you might not know it from your family tree
• 14:11
  Speaker 3: because there's a unique combination of variants from both mother
• 14:14
  Speaker 3: and father, so it may not be so simple as
• 14:17
  Speaker 3: a father or mother family lineage. Now, the reason why
• 14:22
  Speaker 3: it's so important is, Okay, it tells you, yes, you're
• 14:25
  Speaker 3: at high risk or not all right, and if you're
• 14:28
  Speaker 3: at low risk or even moderate, you can feel a
• 14:31
  Speaker 3: lot more assured that that's It doesn't mean you should
• 14:34
  Speaker 3: go out and eat bad things and smoke and whatnot,
• 14:37
  Speaker 3: but at least you're not in this really high risk group. Now,
• 14:41
  Speaker 3: the problem with it is it doesn't tell you when.
• 14:44
  Speaker 3: So just as yes, okay, so it doesn't mean you're
• 14:48
  Speaker 3: have a heart attack, it's probably coming, but we don't
• 14:51
  Speaker 3: know when. It could be when you're ninety, and then
• 14:54
  Speaker 3: you know, maybe you're not even going to live to ninety.
• 14:57
  Speaker 3: You may have something else. So the reason it's different
• 15:00
  Speaker 3: now is we have new models and AI that cannot
• 15:04
  Speaker 3: just tell us like polygenetic risk or added to poly
• 15:07
  Speaker 3: risk or but when that's we never had this before.
• 15:12
  Speaker 2: So you're saying the new model is not just based
• 15:14
  Speaker 2: on the genetics or it's all the things you're talking about.
• 15:17
  Speaker 2: You put in that you put in your scans, you
• 15:18
  Speaker 2: put in everything you can.
• 15:21
  Speaker 3: Put in the whole kitchen sink of data. We call
• 15:24
  Speaker 3: it the stack, right, the stack of data with your proteins,
• 15:28
  Speaker 3: your genetics, your biomarkers, your scans, the retina, the works.
• 15:33
  Speaker 3: And you say, okay, you know what, You're going to
• 15:35
  Speaker 3: have a heart attack at age sixty seven plus or
• 15:39
  Speaker 3: minus a year unless we do some big things change
• 15:44
  Speaker 3: to change that.
• 15:44
  Speaker 2: Well, you just said about that. We put it in
• 15:47
  Speaker 2: and they I said sixty seven plus or whatever. How
• 15:50
  Speaker 2: much how true is that? How much are you kind
• 15:53
  Speaker 2: of making that up? And how much is that actually
• 15:55
  Speaker 2: a thing?
• 15:56
  Speaker 1: Right now? I'm not making it up. This was a shock.
• 15:58
  Speaker 1: This was a big shock.
• 15:59
  Speaker 3: Okay, this is the most exciting thing about AI is
• 16:04
  Speaker 3: predicting preventing disease. Yeah, people talk about accuracy and whatnot. Now,
• 16:09
  Speaker 3: the paper I'm referring to was in the journal Nature.
• 16:12
  Speaker 3: It was done from Morris Gerstung from Germany and his colleagues.
• 16:17
  Speaker 3: And what they did was they took four hundred thousand
• 16:20
  Speaker 3: people in the UK biobank and they basically got their
• 16:24
  Speaker 3: electronic health records and they also looked at polygenic risk
• 16:29
  Speaker 3: for and they could predict twelve hundred different diseases, including
• 16:33
  Speaker 3: heart attack, not just yes or no, but when Yeah,
• 16:38
  Speaker 3: and it works out of sample.
• 16:39
  Speaker 2: It works out of sample.
• 16:41
  Speaker 1: Now you see you had all the right question.
• 16:43
  Speaker 2: Yeah.
• 16:43
  Speaker 3: Then they took it to one point nine million people
• 16:47
  Speaker 3: in Denmark and it was as good or better than
• 16:51
  Speaker 3: in the four hundred thousand UK buy. Okay, okay, So
• 16:54
  Speaker 3: we have it's called it's called the del Phi two
• 16:57
  Speaker 3: M model.
• 16:59
  Speaker 2: Is there enough data on me, just as a normal
• 17:01
  Speaker 2: patient who goes to the doctor every year and is
• 17:04
  Speaker 2: basically healthy to put it into this model? Can I?
• 17:06
  Speaker 2: Can I go use it right now?
• 17:08
  Speaker 3: Well, they're not making it yet available for everyone, but
• 17:12
  Speaker 3: it's imminent.
• 17:13
  Speaker 2: That seems like a big deal.
• 17:15
  Speaker 1: It is.
• 17:16
  Speaker 3: I thought it was one of the most important papers
• 17:18
  Speaker 3: ever published in medicine.
• 17:19
  Speaker 1: I talked, I talked to more. It's about it.
• 17:23
  Speaker 3: He's he's a top flight researcher. There's no hype here.
• 17:27
  Speaker 3: And his team that did this they never expected.
• 17:30
  Speaker 2: It's not even a CT scan, right, it's you just
• 17:33
  Speaker 2: it's data I have already. It's just a smart way
• 17:35
  Speaker 2: to parse that data. That's part of what's so exciting
• 17:37
  Speaker 2: about it, right.
• 17:38
  Speaker 3: Yeah, it's just because as we humans can't see stuff
• 17:43
  Speaker 3: that multimodal AI can see. Yeah, interpret, and that was
• 17:47
  Speaker 3: not even with some of these other things that we've
• 17:49
  Speaker 3: been discussing, right.
• 17:51
  Speaker 2: Right, these are just normal patients who go to the
• 17:53
  Speaker 2: doctor in the UK. They're not getting weird fancy blood
• 17:57
  Speaker 2: tests or scans or whatever.
• 17:59
  Speaker 1: Right, Yeah.
• 17:59
  Speaker 3: And then another major paper in Nature medicine, James Zoe
• 18:03
  Speaker 3: from Stanford did a study that added sleep data to
• 18:08
  Speaker 3: everything electronic record and he did showed the predictive ability
• 18:12
  Speaker 3: was incredible in sixty five thousand people and replicated in
• 18:16
  Speaker 3: another co wort. So our ability to predict heart disease
• 18:20
  Speaker 3: is just all these things that we never knew When
• 18:23
  Speaker 3: you could combine them, it's so formidable. And that's what
• 18:27
  Speaker 3: Then then we have this you know, aggressive ability, Like
• 18:32
  Speaker 3: in your case, we know you're at some higher rest,
• 18:35
  Speaker 3: so we never let you have a heart attack in
• 18:38
  Speaker 3: your life.
• 18:38
  Speaker 1: It's not going to happen. We're going to have to
• 18:40
  Speaker 1: get over.
• 18:41
  Speaker 2: Your lips to God's ears.
• 18:43
  Speaker 1: That we're going to do that in the imminent time ahead.
• 18:48
  Speaker 2: Well, for now, I'm healthy, so I appreciate your sense
• 18:52
  Speaker 2: of urgency. We'll be back in just a minute. Let's
• 19:09
  Speaker 2: talk about drugs, and we're generally about interventions, right, medical
• 19:12
  Speaker 2: and non medical intervention. So clearly we have this incredible
• 19:15
  Speaker 2: new power, very exciting to predict not only who's very
• 19:19
  Speaker 2: likely to have our heart attack.
• 19:20
  Speaker 3: But when and monitor them with those markers. Yes, yes,
• 19:25
  Speaker 3: and even putting them back into the model to see
• 19:28
  Speaker 3: have we changed that predictive Yeah?
• 19:30
  Speaker 2: Yeah? Goodh So aside from like what are the interventions
• 19:36
  Speaker 2: and like what interventions do we have and what interventions
• 19:39
  Speaker 2: do we need that we don't have but we might
• 19:42
  Speaker 2: have soon.
• 19:43
  Speaker 3: Oh well, we start off the statins you mentioned, but
• 19:48
  Speaker 3: other LDL cholesterol drugs.
• 19:50
  Speaker 2: So basically you want to get LDL like so far down.
• 19:54
  Speaker 2: You want to get LDL to like crazy low levels.
• 19:56
  Speaker 3: Yeah, which we can in high risk people.
• 20:00
  Speaker 2: Is it just linear? Is it the lower LDL goes,
• 20:03
  Speaker 2: the lower your risk of heart attack?
• 20:06
  Speaker 1: It looks that way.
• 20:07
  Speaker 3: Yes, I every study when you put them all together,
• 20:12
  Speaker 3: it's a pretty linear result.
• 20:15
  Speaker 1: Yes.
• 20:16
  Speaker 3: But you know, I don't think that it's necessary to
• 20:19
  Speaker 3: be so aggressive with LDL unless you're at very high risk. Right,
• 20:23
  Speaker 3: that's where you get this big bang benefit. But we're
• 20:29
  Speaker 3: too much LDL centric and not enough you know a
• 20:32
  Speaker 3: broader like I mentioned LPA and inflammation.
• 20:36
  Speaker 2: Talk about inflammation, right, I mean inflammation is central to
• 20:39
  Speaker 2: the story you're telling of the mechanism of disease. Right,
• 20:42
  Speaker 2: that's kind of the big shift over these decades that
• 20:46
  Speaker 2: you're describing there. What do we do? How do you
• 20:52
  Speaker 2: lower inflammation?
• 20:53
  Speaker 3: Yeah, so there was a trial called Cantos. It was
• 20:58
  Speaker 3: done with this interluken blocker, all right, and it lowered
• 21:03
  Speaker 3: heart attacks in people who had a high marker CRP
• 21:07
  Speaker 3: for inflammation.
• 21:09
  Speaker 1: There's also these coachesine studies.
• 21:11
  Speaker 3: A lot of people know about coach zine for treatment
• 21:15
  Speaker 3: for gout, but it's an anti inflammatory and there have
• 21:18
  Speaker 3: been some very interesting trials over five randomized trials that
• 21:22
  Speaker 3: show with benefits people with inflammation taking low dose coach
• 21:26
  Speaker 3: zin and a lot of people don't even know that.
• 21:28
  Speaker 3: Doctors don't even know it because they just still think
• 21:30
  Speaker 3: coachuzinees for gout, not for deventing heart disease. Now, what
• 21:34
  Speaker 3: are we going to add to that? Well, what looks promising,
• 21:38
  Speaker 3: what's more impressive than statins, which works through LDL largely
• 21:44
  Speaker 3: is the golp one drugs, Yes, like to zeppethide, zepbound.
• 21:50
  Speaker 2: Weight loss drugs that suddenly everybody is taking. This is
• 21:53
  Speaker 2: what you were talking about. Yes, so let's talk about right.
• 21:55
  Speaker 2: So there's this line in your piece, which is golp
• 21:59
  Speaker 2: one drugs appear to lower the risk of heart attacks
• 22:02
  Speaker 2: a lot. That was unsurprising. The part that was surprising
• 22:05
  Speaker 2: to me was most of the benefit is not from
• 22:08
  Speaker 2: weight loss.
• 22:09
  Speaker 1: I know.
• 22:09
  Speaker 2: That was like, what that's another shocker, right, shocker? So
• 22:13
  Speaker 2: what's going on there? Two thirds of the benefit is
• 22:16
  Speaker 2: not from weight loss?
• 22:17
  Speaker 1: Yeah.
• 22:17
  Speaker 3: So they had the paper when it first came out,
• 22:20
  Speaker 3: the big trial, you know, tens of thousands of people
• 22:24
  Speaker 3: randomized to ozempic or placebo. There was this big benefit
• 22:28
  Speaker 3: of reduction of heart attacks right now. Then they did
• 22:32
  Speaker 3: an analysis because ten percent of people don't lose any
• 22:34
  Speaker 3: weight on ozempic, people don't realize that, and then some
• 22:38
  Speaker 3: people they lose a little weight but not much. Anyway,
• 22:41
  Speaker 3: they found that two thirds of the benefit had nothing
• 22:44
  Speaker 3: to do.
• 22:45
  Speaker 1: With weight loss.
• 22:46
  Speaker 2: That's unbelievable. Yeah, what's going on?
• 22:50
  Speaker 1: Right?
• 22:50
  Speaker 3: So that's that's basically the biggest story about this family
• 22:54
  Speaker 3: of drugs is that their main mechanism of action whell
• 22:58
  Speaker 3: the cosmetic and other health benefits of carrying lesser weight,
• 23:03
  Speaker 3: that's great, But the big impact is to lower total
• 23:09
  Speaker 3: body and brain inflammation.
• 23:12
  Speaker 2: Huh.
• 23:13
  Speaker 1: And they are much more potent stats.
• 23:15
  Speaker 2: And it's clear that the reduction in inflammation is independent
• 23:19
  Speaker 2: of weights less. Presumably weightless alone would drive down inflammation, right.
• 23:23
  Speaker 1: Yeah, but forget about that.
• 23:26
  Speaker 3: If you just have the same amount of belly fat
• 23:28
  Speaker 3: and you're on these drugs and you're seeing big reductions
• 23:32
  Speaker 3: of inflammation, huh, does anybody know why?
• 23:36
  Speaker 1: Well?
• 23:37
  Speaker 3: Yeah, in part, the receptors of the immune cells are
• 23:41
  Speaker 3: rich with GLP receptors, so when you take the drug,
• 23:46
  Speaker 3: it's affecting your immune system, which drives inflammation. So all
• 23:50
  Speaker 3: these drugs work directly through the immune system and also
• 23:54
  Speaker 3: the brain.
• 23:55
  Speaker 1: The brain our command center for inflammation. Right.
• 23:59
  Speaker 3: The brain has GOLP receptors as well. So anyway, we
• 24:04
  Speaker 3: knocked down the immune system, knocked down inflammation. That's something
• 24:08
  Speaker 3: we've never been able to do with a drug safely
• 24:12
  Speaker 3: before statins included. So this is the beginning of a
• 24:17
  Speaker 3: new era of anti inflammatory drugs.
• 24:21
  Speaker 2: Okay, one question, and maybe it's a dumb question, but
• 24:24
  Speaker 2: when you're talking about this sort of immune system being
• 24:28
  Speaker 2: what's modulating the inflammation response, Like, is there any concern
• 24:33
  Speaker 2: about that? Is there are there instances where it's bad
• 24:36
  Speaker 2: that you're taking GLP one drugs and it's suppressing your
• 24:39
  Speaker 2: immune response at some level.
• 24:41
  Speaker 1: Well, that's the difference.
• 24:42
  Speaker 3: In that earlier trial I mentioned Cantos with the endo
• 24:45
  Speaker 3: lukeing of blocking. The problem was they reduced heart attacks,
• 24:49
  Speaker 3: but it increased infections. Right here, we don't see any
• 24:54
  Speaker 3: increased infection. And that's what's so exciting is that we're
• 24:58
  Speaker 3: we're so more selective. We're not blocking the immune system
• 25:01
  Speaker 3: that defends us. We're blocking the immune system that hurts us.
• 25:05
  Speaker 3: But they're not the end of anti inflammatory drugs.
• 25:09
  Speaker 2: Another one more.
• 25:10
  Speaker 3: Oh gosh, there's the n l RP inflammazome. There's the
• 25:14
  Speaker 3: gas sting pathway. I mean, these are your listeners, you
• 25:19
  Speaker 3: know they All I can say is there's so much
• 25:22
  Speaker 3: more going on right now to reduce inflammation with more
• 25:26
  Speaker 3: gut hormones, with new drugs, new pathways, with gut microbiome manipulations,
• 25:32
  Speaker 3: changing the gut microbiome or it's metabolis. We are on
• 25:36
  Speaker 3: the inflammation express Okay, anti inflammation. You're going to see
• 25:41
  Speaker 3: a blossoming of strategies to block untoward inflammation like never
• 25:46
  Speaker 3: before in medicine.
• 25:48
  Speaker 2: So let's talk about the like I don't know the
• 25:50
  Speaker 2: medium to long term future. What does the field look like.
• 25:53
  Speaker 2: What does your job look like?
• 25:55
  Speaker 3: Well, it ought to be revamped today or you know
• 25:58
  Speaker 3: in the next year. As you know, medical community doesn't
• 26:04
  Speaker 3: change very quickly, but eventually it will be incorporating all
• 26:09
  Speaker 3: the things we've discussed today. You are head of the
• 26:12
  Speaker 3: curve by getting apologenic risk, and I give you a
• 26:14
  Speaker 3: lot of credit for that.
• 26:15
  Speaker 2: It's just a lucky break. I just happened to walk
• 26:18
  Speaker 2: into the right doctor's office at the right time.
• 26:20
  Speaker 3: It should be in everyone with a family history or
• 26:22
  Speaker 3: other risk factors. That should be you know, it's cheap,
• 26:25
  Speaker 3: it could be done. We can do it for like
• 26:27
  Speaker 3: twenty dollars.
• 26:28
  Speaker 1: You know.
• 26:29
  Speaker 3: You can actually now if you have your ancestry DNA
• 26:34
  Speaker 3: or twenty three and meters, you can use one of
• 26:38
  Speaker 3: the AI platforms like a cloud or open AI and
• 26:44
  Speaker 3: can analyze and give you your apology.
• 26:46
  Speaker 2: Interesting.
• 26:48
  Speaker 3: Yeah, so anyway we should have that. It will become accepted.
• 26:53
  Speaker 3: So will be the artery score, the heart score, the
• 26:56
  Speaker 3: brain organ clocks, so will be these better inflammation markers
• 27:02
  Speaker 3: and the models we talked about, they will become routine
• 27:05
  Speaker 3: and each you could even have a virtual coach and
• 27:10
  Speaker 3: you say, your virtual coach will say your new assessment
• 27:14
  Speaker 3: with your sleep and your exercise, and you know, whatever
• 27:17
  Speaker 3: test has changed, the chance of you having a heart
• 27:21
  Speaker 3: attack at age sixty seven is now changed to age
• 27:24
  Speaker 3: seventy nine. Yeah, wouldn't that be nice.
• 27:30
  Speaker 2: We'll be back in a minute with the lightning rip.
• 27:43
  Speaker 2: I read an interview with you recently and you said
• 27:47
  Speaker 2: chatbots are more empathetic than doctors. Yeah, which I found
• 27:50
  Speaker 2: extremely interesting coming from a doctor. Tell me more.
• 27:54
  Speaker 3: AI has no clue what empathy is, no clue, but
• 27:59
  Speaker 3: it channels all of its language training to basically be
• 28:06
  Speaker 3: a great way to support empathy. It's a far more impressive,
• 28:15
  Speaker 3: at large empathetic channel than the average doctor. The average
• 28:21
  Speaker 3: doctor doesn't have time. And it turns out there's been
• 28:25
  Speaker 3: thirteen studies and twelve of them have shown that by
• 28:30
  Speaker 3: doctors making the judgment that the AI was more empathetic
• 28:34
  Speaker 3: than the doctors.
• 28:36
  Speaker 1: Say WHOA.
• 28:37
  Speaker 3: Now, the other thing that's surprising here is that we're
• 28:41
  Speaker 3: going to see AI coaching doctors to be more empathetic.
• 28:46
  Speaker 3: They're going to go over their notes. This is the
• 28:48
  Speaker 3: conversations and they say, well, doctor Smith, why did you
• 28:52
  Speaker 3: interrupt missus Jones after nine seconds? She never even had
• 28:56
  Speaker 3: a chance to express what was her concern and that
• 28:59
  Speaker 3: stuff like that.
• 29:00
  Speaker 2: How do you think doctors will take that? I could
• 29:03
  Speaker 2: have matter a doctor not wanting to hear from an AI.
• 29:05
  Speaker 3: Yeah, well, you know, the data is accruing and it's
• 29:09
  Speaker 3: not good for doctors.
• 29:10
  Speaker 1: It's not their doctor's fault.
• 29:12
  Speaker 3: It's because there's squeezed so much to see so many
• 29:15
  Speaker 3: patients in such short periods of time.
• 29:17
  Speaker 2: Yeah, how do you use AI in your in your
• 29:23
  Speaker 2: non work life? How do you use it when you're
• 29:25
  Speaker 2: not working?
• 29:26
  Speaker 1: If you use it, I use it a lot. I
• 29:30
  Speaker 1: use it.
• 29:31
  Speaker 3: I use deep research a lot when I'm curious about
• 29:35
  Speaker 3: something and I just want to produce a report.
• 29:38
  Speaker 2: What was a recent thing you used deep research for
• 29:41
  Speaker 2: outside of work?
• 29:42
  Speaker 3: Well, like today, there was a publication about the real
• 29:46
  Speaker 3: da Vinci code of Leonardo da Vinci.
• 29:48
  Speaker 2: Okay, I didn't know that was a real DaVinci code.
• 29:50
  Speaker 3: Well, it's in the works, So I did.
• 29:53
  Speaker 1: I did a.
• 29:55
  Speaker 3: Query about what do we know about Leonardo da Vinci's
• 29:59
  Speaker 3: geno and the answer was, you know very little actually,
• 30:03
  Speaker 3: But I mean that this curiosity, I wasn't like writing
• 30:07
  Speaker 3: any paper about it. It's just, you know, it's just
• 30:10
  Speaker 3: the way my crazy mind works.
• 30:12
  Speaker 1: Yeah.
• 30:14
  Speaker 2: What are you worried about with respect to AI?
• 30:16
  Speaker 1: Oh? Lots of things. Okay, I'm worried about.
• 30:20
  Speaker 3: There's lack of transparency, there's lack of compelling data in
• 30:25
  Speaker 3: many respects that have accrued. There's worries about implementing it
• 30:31
  Speaker 3: where you could have adversarial attacks. There's privacy, security issues,
• 30:35
  Speaker 3: there's inequity issues.
• 30:36
  Speaker 1: Worth thing.
• 30:37
  Speaker 3: I mean, there's a long list here.
• 30:39
  Speaker 1: Okay.
• 30:40
  Speaker 3: Of course there's errors and hallucinations, but we don't acknowledge
• 30:43
  Speaker 3: human errors enough. We think that AI has to be
• 30:46
  Speaker 3: perfect and it's never going to be perfect. But no,
• 30:50
  Speaker 3: so there's issues with AI that we have to confront
• 30:54
  Speaker 3: head on to make it better and be more pure positive.
• 30:58
  Speaker 2: Okay, last thing, forget about AI. Let's just talk about
• 31:02
  Speaker 2: the heart of cardiovascular system. What's one thing you wish
• 31:06
  Speaker 2: we understood that we don't understand about how it works.
• 31:10
  Speaker 1: That's a good one.
• 31:13
  Speaker 3: Well, I mean, I the inflammation story that we discussed,
• 31:20
  Speaker 3: I've given you the reductionist view. Yeah, I've oversimplified it.
• 31:26
  Speaker 3: I'd like to know all the intricacies of that. I'd
• 31:29
  Speaker 3: like to know why people that do everything right and
• 31:33
  Speaker 3: have low LDL and low everything that we can measure
• 31:37
  Speaker 3: still can get inflamed arteries and a heart attack.
• 31:40
  Speaker 1: We don't know why. I'd like to know exactly what's
• 31:43
  Speaker 1: going on there.
• 31:44
  Speaker 3: And so there's things that we don't understand that I
• 31:47
  Speaker 3: hope eventually will unravel. Anything else you want to say, Well,
• 31:53
  Speaker 3: I've really enjoyed this discussion. You're the first one that's
• 31:56
  Speaker 3: really you know, come to discuss this cardiovascular change of
• 32:01
  Speaker 3: the big miss or you know, the.
• 32:03
  Speaker 2: Completely talking about it for twenty years. Nobody ever interviewed
• 32:07
  Speaker 2: you about it.
• 32:09
  Speaker 3: In recent time, not with all the things that we
• 32:11
  Speaker 3: discussed today. So I thank you for that. Thanks for
• 32:14
  Speaker 3: queueing into what I think is really important.
• 32:23
  Speaker 2: Eric Topel is a cardiologist and the founder of the
• 32:26
  Speaker 2: Scripts Research Translational Institute. Please email us at problem at
• 32:31
  Speaker 2: Pushkin dot fm. We are always looking for new guests
• 32:35
  Speaker 2: for the show. Today's show was produced by Trinamanino and
• 32:39
  Speaker 2: Gabriel Hunter Chang. It was edited by Alexander Garreton. And
• 32:43
  Speaker 2: engineered by Sarah Brigett. I'm Jacob Goldstein and we'll be
• 32:46
  Speaker 2: back next week with another episode of What's Your Problem.