B (5:25)

I know that some doctors use certain risk calculators and actually go over them with patients in the room and kind of plug in their numbers in front of them in order to show them, you know, actual cold, hard data. Especially if, like you said, they're hesitant about starting medication or just starting to think about things for the first time. Do you ever do things like that and do you kind of show them risk calculator.

A (5:46)

I'm gonna give you an answer that you don't like, which is like, I am so anti risk calculator.

B (5:50)

Oh, really?

A (5:51)

The reason for that is I think they're great on a population level, but I think that they miss a lot of younger people who are at elevated risk. And the reason that they miss younger people who are at elevated risk is that the biggest thing that drives risk on those calculators is age. You know, if you look at all of these guidelines, the guidelines will describe the decision about starting medical therapy based on what somebody's level of risk is according to one of these calculators. And I think it gives us the illusion of confidence that we understand what somebody's actual risk is, because if this guy has a heart attack, his chance of having a heart attack was 100% risk calculator be damned. And so I think that the risk calculators are great for sort of, put it, ballparking things. But in terms of the actual decision for a patient about starting medical therapy, for me, it's. I can't remember the last time a risk calculator actually influenced me, because if somebody has elevated blood pressure, treating that elevated blood pressure lowers their cardiovascular risk. And the relative risk reduction that you get is going to be pretty similar. It's going to be somewhere between 25 and 40% of a relative risk reduction for optimally controlling all of these different risk factors over a period of three to five years. But when you treat somebody who's this guy is 62 years old, and so theoretically you don't. I'm not looking, how can I get him to 72 without a heart attack? I'm thinking about how can I get him to 92 without a heart attack? Risk increases as time goes on because all of these different risk factors are exposure over time. And so if I have patients who are mathematically inclined, I will talk to them about the concept of area under the curve. It's like saving for retirement, where if you start saving younger, you have to save a little bit less each month versus the later you start, the more aggressively you need to lower risk factors. And so it's not wrong to open up a risk calculator and to show somebody what their risk is over the next 10 years. But I think that you miss a lot of young people who are at risk. And you under treat young people, you over treat old people. And for me, this guy has untreated risk factors for cardiovascular disease and he has a family history of early heart disease. And there's no number I'm going to see on a risk calculator that's going to persuade me that we shouldn't treat him.

B (8:07)

Well, when you put it like that, it definitely makes a lot of sense. From my own experience more in residency, you know, if I were seeing a patient in clinic and we were talking about starting medication, often what would come up is, well, maybe I can exercise or change my diet first. And when patients would say that it was kind of, I had a mixed reaction. One was, okay, well at least there's less work to do and less follow up and I don't have to start a new medication on this patient. But at the same time, you kind of have a little bit of doubt that that's going to make a really significant difference. Do you have patients for whom you would advise going that route first? I know maybe not in this patient, given how many risk factors he has, but what kind of patient would you advise that first?

A (8:48)

So I don't think it's a binary discussion of lifestyle modification or medical therapy. I'm in the both end camp, not the either or camp. And you know, for a disease like cardiovascular disease that is so multifactorial and affects so many people, you usually want to, you want to address it from multiple different angles. And I will always spend time talking with a patient about eating better and about staying more active. But the reality is, if you look at the data on adherence to exercise regimens or consistency of weight loss in the pre GLP1 drug era, the data kind of sucked. It's really easy to fall into the trap for patients of, you know, let's just give it three months and then let's give it six months. And, oh, the holidays came around and I fell a little bit off. And so I'm a little bit sort of out of shape and off my diet. And so let's just wait a couple of more months, and all of a sudden you look up and it's three years later, and the risk factors have been uncontrolled. And so it's not that I ever discourage a patient from implementing a healthy lifestyle or from making the changes that I think are so important. It's that making those changes or the process of making those changes doesn't actually, for me, change how much I'm going to want to get the risk factors under control and how quickly I'm going to want to get the risk factors under control. The other thing is, like, especially so blood pressure generally will respond pretty well to weight loss, to more physical activity, to an improvement in diet, sometimes a reduction in sodium, sometimes an improvement in sleep or stress management. But LDL doesn't budge that much. And so if patients are eating an awful diet, meaning a lot of fast food, tons of soda, really, really sort of just up very far away from everybody's idea of a healthy diet, then you can get a pretty big drop in the numbers. But if you have people who are eating in a generally healthful way, the amount of drop that you get in LDL is just not as impressive as we would think that it is. And so I sometimes tell patients that, you know, you could eat nothing but steamed broccoli and exercise for a couple of hours a day, and I would probably still want to lower your risk with medications. And it all comes down to what is your perception of this individual patient's risk? What is the patient's perception of their risk? How do they feel about medications? But I don't think that it's a decision about should we do lifestyle modifications or should we think about prescription meds. It's really a conversation about how do we get your risk under control as quickly as possible?

B (11:15)

How do you generally approach the conversation of starting a statin? And both in terms of your conversation with the patient and also how do you look at their lipids and how do you think about APOB and LP.

A (11:28)

When it comes to starting a statin? The discussion with a patient really depends on how much time they spend on the Internet, and especially like in the wellness section of the Internet, because if you are really online, you have a Very skewed perspective on the risks of statin therapy. And so I sort of bring up the concept and I hear what somebody has to say, and I get a sense of what they've read and what they know. Before I start sort of pushing, you should be on a statin. I think we should prescribe your rosuvastatin or forvastatin. But going back to the other part of your question, how do I use things like the lipoprotein little A and evil lipoprotein B? So they're very, very different in terms of use, and they often get lumped together as part of an advanced lipid assessment. But they're. They're tools that really any physician can use. And so I look at lipoprotein little A or LP as something that is a real signifier of genetically mediated cardiovascular risk. And LP is a lipoprotein that's a combination of an LDL particle with an apol lipoprotein called apolipoprotein lowercase A. That's different than apolipoprotein A, which is the lipoprotein in HDL cholesterol. LP is problematic because it is really atherogenic. It's pro thrombotic and it's pro oxidative, and it's really linked. For a lot of patients, an elevated LP means an aggressive early phenotype of cardiovascular disease. And so LP is something that needs to be checked one time for everybody. The drugs to directly treat it are still in clinical trials. And so it's one of those things, you get it, and then patients start reading about their LP is 200, they start googling, what does that mean? And it can really freak people out. The way I explain it to patients is this is one piece of information about thinking about your risk. And when it's elevated, what that does is it influences me on the margins about adding another blood pressure medicine or starting a blood pressure medicine or getting your LDL down to 55 instead of 70 may change our decision about should we start a GLP1 agonist? So LP is a. It's one of those things where when I'm on the fence about should I do something or should I not? A high lp, especially when coupled with an early family history of heart disease, pushes me towards more aggressive medical therapy, the APOB test. So apolipoprotein B is the lipoprotein that is on all of the particles that cause cardiovascular disease. Every single atherogenic lipoprotein has one APOB molecule on it. And most of Those lipoproteins are LDLs. The reason that APOB is a good test to use in patients is there's a certain proportion of patients who will have a discordant LDL cholesterol compared to their abo lipoprotein B. And the way that I think about it is when we want to understand cardiovascular disease risk, it's almost like traffic. We want to understand what's the traffic of particles in your arteries that can cause cardiovascular disease. And when you measure somebody's ldl, what that tells you is it tells you how many people are traveling up the street. But if you want to know what's going on with traffic, you actually want to know how many cars are on the road and APOB tells you how many cars are on the road. Instead of just understanding there's a thousand people traveling up First Avenue, I want to know are they in 10 buses or a thousand individual cars? And the APOB helps to inform you about whether that is concordant with their LDL or not. And so I'll usually for most patients, check an APOB once to see is the percentile of APOB the same as the percentile of ldl. And if it is, that probably says to me, I can just check ldls moving forward and that's going to be good enough. If it's out of proportion to what it should be based on what the LDL looks like, then APOB is definitely a better marker to be tracking in terms of how are the lifestyle modifications working and how is the medical therapy doing what we want it to do. And so APOB can be really informative. And the people for whom it tends to be most informative in are people who have metabolic syndrome. And so this is a patient, this 62 year old man who has an A1C of 7.8, who clearly is insulin resistant. And people who are insulin resistant and have metabolic syndrome, even if it has not progressed to full diabetes, will often have an APOB that is high out of proportion to what you would expect based on their ldl, you can have a suggestion, just based on a regular lipid panel that somebody is going to have a high APOB compared to their LDL. By looking at the ratio of triglycerides to HDL, an ideal triglyceride to HDL ratio is 1 to 1 above 2 to 1. I'm starting to get a little bit suspicious about insulin resistance. When it's greater than three to one. That really makes me suggestive that patients are going to be insulin resistant. It's incredibly common in folks with diabetes or pre diabetes or well controlled glucose, but abdominal adiposity to have a ratio that is 15 to 1, 10 to 1. That lipid panel of the triglycerides are 250 and the HDL is 25. It's, it's the sort of thing, once you start looking for it, you're going to see it over and over and over again. And those are the patients for whom particle number dictated by apob is actually a much better predictor of risk.

B (16:46)

That is fascinating and I like the traffic analogy. Let's say this patient listened to everything you have to tell him. He's been sufficiently scared about his risk profile and he agrees to start a statin. What do the next couple of months look like as far as follow up and repeating labs?

A (17:03)

Before I start a statin, I always counsel people on side effects. And so side effects are common with every drug. And it's often the first question that patients, I'm sure you've had patients ask, what are the side effects of this drug when you recommend prescribing it? It doesn't really matter what the drug is. And so I tell people somewhere around 8 to 10% of people will have a little bit of muscle aches. And if you have muscle aches, you usually start somewhere between one and three weeks after starting the drug. And it always goes away after you stop the drug. And so this is a low stakes decision about starting it because if you have a side effect, we stop the medicine and the side effects go away. Usually check the transaminases. Sometimes you'll see a little bump in the transaminases, but unless it's a really, really profound rise, it doesn't really have much clinical roundness. And then the other thing that I'll pay attention to is their, their A1C or at least their fasting glucose because there is a little bit of worsening glucose tolerance caused by especially being on particularly high potency statins. And so sometimes you'll see a rise in a 1C of 0.1 or 02 when somebody's been on 40 over a suvastatin. And it's just something that is on my mind and something I want to keep tabs on how low we try to get the ldl. It really depends partly on somebody's age, partly on somebody's risk, partly on whether they've got any, any imaging evidence of asymptomatic atherosclerosis. And if you look at sort of all of the clinical trials, what you see is that when it comes to LDL or apob, lower is better. And so in general, I have the same principle for lipids that I have for radiation, which is Alara, or as low, as reasonably achievable. And so somebody's doing well and they have a good reduction in their LDL on a low dose of a statin. And I this patient whose LDL is 130 goes down to 65 by being on 5mg or 10mg over Suvastatin. I'm probably okay for that for from a primary prevention perspective. But if I have any reason to suspect that this patient actually is having sort of a higher risk, whether it's other uncontrolled risk factors or maybe there was a possible TIA in the past that came out the second time I was seeing them, maybe I would aim for a goal that was closer to 50. But the goal that you are aiming for is really going to be dependent on how do you perceive somebody's risk to be. Risk is, it's pretty clear from lots of randomized trials, lots of observational studies, even the Mendelian randomization, lower LDL and lower for longer tends to be linked with lower risk of heart attacks and strokes.

B (19:39)

One other medication I wanted to ask you about, I know aspirin is sometimes used in primary prevention. How would you determine whether you want to start aspirin as well?

A (19:48)

You can make the aspirin story really complicated, or you can make it really simple. And in general, aspirin slightly lowers your risk of having a heart attack or a stroke, and it increases your risk of having a clinically significant bleeding complication by about the same absolute amount. And so I think about aspirin as being something that if I have somebody who has very uncontrolled risk, they're a heavy smoker, they have a really high lp, we can't get their other risk factors under control, I would think about using an aspirin. But in general, the data really sort of suggests that the majority of patients don't get a benefit in aspirin for primary prevention and it's better utilized as a secondary prevention drug. But that said, there's going to be a subset of people for whom aspirin as a primary prevention choice actually makes sense, and that risk benefit profile is more favorable. But that's an individual discussion, and every patient's a little bit different when it comes to that, that choice.

B (20:45)

You touched on this a little bit earlier, but how do you factor in cardiac imaging into this initial risk profiling.

A (20:52)

And workup cardiac imaging within the form of coronary calcium scores or coronary CTAs or carotid ultrasounds. Those are controversial in some areas of the. Of the prevention space, because on one hand, there has never been a randomized trial showing that using those tests to guide our treatment strategies makes outcomes any better. On the other hand, a good trial actually asking that question hasn't really been done with the power to tell us whether that's a true thing or not. And so I use those tests to help me in a couple of different ways. One is a patient who is very much on the fence about medical treatment, but for whom I think medical treatment is really indicated, because my perception of their risk is that it's quite high. And so sometimes a patient seeing that there is calcium present in their coronary arteries really, really persuades them that this is something that they need to get under control. And they've been on the fence about a medication. And then all of a sudden, you see clear, unequivocal imaging evidence that there is calcium in the arteries. And patients all know the term hardening of the arteries. You can pull up a CAT scan and you show them that there is this bright white substance in your lad. It really changes how people think about their risk, and it really changes the seriousness with which people will consider medical therapy. A carotid ultrasound, I think, is a similar test in that it can detect the presence of asymptomatic atherosclerosis, subclinical atherosclerosis, years, if not decades, before it causes a patient to have any symptoms. And so I use those tests for people who are on the fence about whether I should start treatment, for people who are personally themselves on the fence about whether they should start treatment, or for anybody who I'm trying to more precisely understand what their cardiovascular risk is. A couple of caveats with the coronary calcium score. So, number one, coronary calcium score does not help for the evaluation of somebody having chest pain. Number two, you can have a lot of coronary disease and still have a calcium score of 0 because not all plaque in the coronaries has calcified him. And so if you have a young patient under the age of 40 or 45 or maybe even 50, a coronary calcium score is kind of a useless test, because if it's zero, well, it's supposed to be zero. And the only way that you have confidence that you understand somebody's actual presence of coronary disease is you need a coronary CTA to see soft plaque. And the older People are, the more reassuring a calcium score of 0 is, the younger somebody is, the less helpful a calcium score of 0 is. But if you have somebody who's young, meaning under the age of 50, who has a calcium score of anything over zero, that to me is a real red flag that somebody's at elevated risk much more than would be sort of estimated by any of the risk calculators. And so these imaging tests can be really helpful for an individual patient in the aggregate. I think that they probably modify risk for probably 20 to 30% of patients for whom it will influence your decision about starting a medicine versus not.

B (23:51)

One last question to wrap things up. Thinking a little bit more about his comorbidities. I know we spoke earlier about how overall they increase his risk profile, but how do you think about managing them? I know some of us are lucky enough to work in hospitals where there may be multidisciplinary teams with pharmacists who can reach out to patients after starting new medications, or nutrition teams who can help with healthy eating and exercise. But I'm particularly curious about your experience with GLP1 agonists, given how important weight loss and weight management is in cardiovascular health. Is this something that you will refer out or do you kind of take it on yourself?

A (24:30)

GLP1 agonists are cardiovascular drugs, and you can look at the select trial like there is evidence that these drugs lower cardiovascular disease risk. And so I look at the role of the cardiologist as being the person who is completely capable. And it is completely appropriate for that doctor to prescribe a GLP1 agonist. There's pretty clear data in secondary prevention of cardiovascular disease that semaglutide lowers the risk of cardiovascular events. It's not insane to extrapolate that to tirzepatide as well. And so I'm prescribing these drugs a lot. And for this patient, you could make a really compelling argument. His BMI is 32, his A1C is 7, 8. Maybe instead of putting him on a blood pressure medicine and a lipid lowering medication and metformin, you should just put him on tirzepatide at 2.5 milligrams once a week. And that's actually going to bring the blood pressure down because of the way that it influences weight loss. And it's going to get the glucose under control and it's going to help get the metabolic profile looking a little bit better. And so you could make a compelling argument that instead of treating all of these individual things, just throw them on a little bit of tirzepatide, which is Mounjaro or Zeppelin. And that's the initial approach that has not come to be sort of the standard of care just yet, but it might be 10 years from now.

B (25:47)

All right, Mr. K. Tells you that he's very motivated to make all of the changes that you spoke about during this appointment and excited to be a better and healthier version of himself. Dr. Katz, do you have any final thoughts to leave us with as we wrap up this episode?

A (26:02)

I try to empower patients that a lot of their cardiovascular risk is really able to be controlled and that even though this is the most likely reason why human beings on planet Earth die, it doesn't have to be. And so if you're able to identify and treat the things that cause cardiovascular disease, you can completely change the trajectory of somebody's lifetime risk.

B (26:24)

Thank you so much, Dr. Katz, for this incredibly comprehensive overview. We hope you'll join us again soon on Run the List.

A (26:30)

My pleasure. Thanks for having me. Some content from this episode was generated with the assistance of artificial intelligence.