Ep. 51: The Number Is Not the Outcome — with Dr. Regina Druz, MD, MBA, FACC, FMCP-M

Does lowering LDL cholesterol prevent your next heart attack? Three trials put that question into sharper focus this year — STAREE, AMUNDSEN and Lp(a)HORIZON — and the answer turns on one idea most patients never hear about: absolute risk reduction. In this remix episode, Dr. Regina Druz explains why a better lab number is not the same as a better outcome, and brings back voices from earlier conversations — Dr. Ernst Schaefer on how low LDL should go, Dr. Kim Williams on statins and plant-based eating, and Dr. Guy Mintz on lipoprotein(a) — before closing with residual risk, vascular age, and three questions to ask your own doctor.

Watch on YouTube: A video version of this episode is available on the Own Your Heart Health YouTube channel. Subscribe to be notified of new episodes.

Episode Chapters

[00:00] An 82% LDL Goal With No Significant Outcome Difference
[01:30] Statin Trial Results in Adults Over 70
[03:00] PCSK9 Shot Before the Cath Lab
[04:50] Lipoprotein(a) Drug Trial Misses Its Primary Endpoint
[07:30] Relative vs Absolute Risk Reduction Explained
[11:30] Cholesterol Matters and How Low to Go
[22:00] Dr. Guy Mintz on Lipoprotein(a) Strategy
[31:20] A 56-Year-Old’s Calcium Score and Vascular Age
[38:00] Residual Risk and Personalized Risk Estimates
[41:30] Three Questions to Ask About Your Risk

Transcript

[00:00] An 82% LDL Goal With No Significant Outcome Difference

Dr. Regina Druz (00:02): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week, we will dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Last month, a trial got 82% of heart attack patients to their LDL goal, but a year later, their outcomes were not different. I’m Dr. Regina Druz, and this is Own Your Heart Health Remix. Here’s the pattern I want you to see. The number on your lab report and what happens inside your arteries are related, but they’re not the same thing.

This is not an anti-statin episode or a pro-statin episode. You’ll hear guests who use these drugs every day, including myself, Dr. Ernst Schaefer on as low as reasonably achievable, Dr. Kim Williams on where statins fit with a plant-forward diet, Dr. Guy Mintz on why he still lowers LDL first in his lipoprotein(a) patients. And you’ll hear me on relative versus absolute risk reduction, the most important math in cardiology that almost nobody does out loud.

The question was never statin or no statin. The question always is: is the medication the right medication for you, the right person, and for the right length of time to take that medication? First, what just happened is that over the past months we had three interesting results. And together they tell one story.

[01:30] Statin Trial Results in Adults Over 70

First, the STAREE trial. And I talked about that trial a little bit in my prior episode. Nearly 10,000 adults over 70, no heart disease, no diabetes, were given atorvastatin, which is a very common statin medication, fairly significant dose, 40 milligrams.

Dr. Regina Druz (02:17): And compared to the group that received the placebo medication — all of these adults had elevated LDL cholesterol, but it wasn’t too high. It was mild elevation. And they were followed for almost six years. Now the cardiovascular events, relatively speaking, fell by 30%. That’s the headline. That’s what you’re going to see on the internet. But in absolute terms, 6% of people on a statin had an event versus 8.3% in the placebo group. So there was literally a difference of 2.3 percentage points, which worked out to treating about 44 people for six years to prevent one event, right? So the number needed to treat was one in 44, the time to therapeutic benefit was six years. And the trial’s other primary endpoint — reduction in disability, reduction in dementia, reduction in death — did not move.

Right. So most of the death actually in that trial was not cardiovascular at all, right? So it was interesting because these were relatively healthy, older type of patients.

[03:00] PCSK9 Shot Before the Cath Lab

Second study was AMUNDSEN. AMUNDSEN came out slightly, you know, earlier in the summer and had about 2,000 people who were in the midst of having a heart attack. They were being taken to the catheterization laboratory to look at their arteries, give them a stent. And right before they had gone for that procedure, they were injected with Repatha, which is a PCSK9 inhibitor. 82% of them reached their LDL goal. This was a very aggressive LDL goal. And with such a powerful drug, they reached it, versus 40% who were treated more conventionally. And so certainly a huge win on the laboratory report.

And then these patients were followed for 12 months. And what was found is that the events did not differ between the group that got an injection and the group that didn’t get an injection. Now remember, both of these groups were actually treated fairly aggressively. The only difference was that one group got a Repatha injection, got literally a single shot on the way to the cath lab, and then obviously they continued the medication, and then another group

Dr. Regina Druz (04:40): got statins and other medications, but did not get Repatha.

[04:50] Lipoprotein(a) Drug Trial Misses Its Primary Endpoint

And so finally, to round out the trials, we come to a study called Lp(a)HORIZON, right? And stick with me — in November, the American Heart Association meeting will actually provide us with the full report of the HORIZON trial.

What the company that performed the trial, Novartis, released is actually so-called top-line results, right? They didn’t publish the whole study, it wasn’t peer-reviewed, they simply released top-line results. And so this was a very interesting trial that studied a very novel medication called pelacarsen, which was specifically developed to lower lipoprotein(a), right? So it’s really, you know, to answer a question that we all have in our minds. We know that lipoprotein(a) is impactful. It is a risk amplifier. We know this from multiple studies. We know this from genetic studies. We know this from clinical studies. We had all seen these patients with premature coronary artery disease or patients with aggressive disease with elevated lipoprotein(a).

So the hope was that once a drug is there that is specific to lowering lipoprotein(a), we will see a reduction in cardiovascular events. But that did not happen. Now we don’t know what exactly happened in the trial yet, how much lipoprotein(a) reduction people had. Lp(a)HORIZON studied patients for secondary prevention, which means that those patients already had events.

They were already treated very aggressively with lipid-lowering medications and other cardiovascular medications. So they were a well-treated, aggressively treated group. And perhaps in a group like this, lowering lipoprotein(a) was not as impactful. So what we ended up with is three drugs, right — statins, Repatha and a novel medication for lipoprotein(a), pelacarsen — three different patient populations.

Dr. Regina Druz (06:59): One pattern: a number can move in weeks, but the biology of your arteries may not move at all. And if it does, it may take years. And so now, what this is not — this is not proof that medication doesn’t work, or that statins don’t work, or that Repatha doesn’t work, or that pelacarsen doesn’t work. What it tells us is that getting the right biomarker affected in the right person over a certain period of time may be impactful for cardiovascular events, but a lot of it depends on the context. So what these trials tell us is that the lab number is a guide, it is not a destination. And I think this so often gets lost in the clinical environment. You know, patients and even physicians are very much focused on laboratory parameters, on rechecking laboratory parameters over and over, but remember that the number is just a number. And you know, between the number and the impact on the arteries, there is a long road to travel, right? A single number, and reduction in a single number, does not necessarily translate into an improvement in vascular risk.

[07:30] Relative vs Absolute Risk Reduction Explained

So what I would like you to listen to in this remix is diverse voices and different opinions. So let’s start with the math that I already mentioned earlier that every patient should know, right? Relative versus absolute risk, number needed to treat, and what it actually means. If we line up all the patients that were participating in these studies, and we compare a group of patients that were treated with medications or interventions to reduce LDL cholesterol, and a group of patients who were just given a placebo — and you know, their cholesterol levels were not reduced with medications — the difference between those patients in terms of cardiovascular events was 30%, and that’s a relative difference. So for example,

Dr. Regina Druz (09:15): we could say that in a group of patients who were not treated — let’s say we took 100 patients and we determined at the end of our trial that in that group of 100 patients who were not treated with an LDL-lowering intervention, 10 patients had some sort of a cardiovascular event, right? So you could say, well, this is an event rate of 10%, right?

So, an event rate of 10% is nothing to sneeze at. It’s not particularly high, it’s not particularly low. It really depends on what disease you’re studying. But let’s say there was another group of patients in this very same trial, also 100 people. They were very similar in terms of their characteristics to the group that didn’t receive any cholesterol-lowering medication. And that actually was our intervention group.

And that intervention group had received LDL-lowering treatment. And as a result, they have reduced their event rate by 30%. So what that means is that instead of a 10% event rate, the reduction by a third places them somewhere around 7%. So it’s not that they didn’t have any events, they just had fewer of them, right?

And so this is one of those situations where a relative risk is a very big number, right? It’s 30%, but the absolute risk reduction is actually much smaller than that. It’s 3%, because our group that didn’t receive treatment was a 10% event group, and the group that received the medication was 7%. So the difference between these in absolute percentage points is 3%.

But the relative difference, of course, is 30%. So you could see that sometimes, when we talk about relative risk reduction, it tends to make the numbers very large. But the absolute risk reduction may actually be significantly smaller. And the reason why we care is because absolute risk reduction can be translated into something called number needed to treat.

[11:30] Cholesterol Matters and How Low to Go

Dr. Regina Druz (11:32): And we will talk about number needed to treat. But for now, what I want you to remember is that LDL cholesterol is very important, because this 40-30-20-10 rule does apply. It’s the 44 you just heard about. A few months before that episode, I launched a series called S.O.S., the Statin Overprescribing Solution. And I opened it with something a seasoned cardiologist friend said to me. Listen to what they said, and then listen to what I say right after. Cholesterol does matter.

Clip from Episode 16 — Statin Overprescribing Solution (S.O.S.) Part 1

Dr. Regina Druz: It really came into focus for me recently because I asked one of my friends and colleagues, who is a very seasoned, very experienced, wonderful cardiologist with both academic and private practice experience, their opinion of carotid intima-media thickness. And my colleague said, “Well, I do check it from time to time. I check calcium score from time to time, but, you know, I don’t see a whole lot of value in those techniques because all I know how to do is to lower LDL cholesterol,” right? So this has been the main road cardiology has traveled for decades, this cholesterol-centric hypothesis. And we know now from the mainstream cardiology literature, from the leading investigators, including the ones in some of the most esteemed academic institutions, such as Harvard Medical School — Dr. Paul Ridker, Dr. Peter Libby, giants in cardiology — we know from their work that the cholesterol-centric hypothesis is outdated. Does cholesterol play a role in atherosclerosis? Absolutely.

So if you really are under the impression, from some of the internet chatter, that cholesterol doesn’t matter for your arteries — please stop listening to this, because it’s simply not the reality. It’s a myth. Cholesterol does matter for your arteries. We have population-level data, but more importantly, with the integrative cardiology approach, we can get your level of data, N of one, and tell you

Dr. Regina Druz (13:52): if cholesterol is mattering for your arteries, and how much, and what you can actually do about it. But my friend says, you know, all I know how to do is to lower LDL. So what is really the point of, you know, being a little fancier and going for those other tests? And I’m going to argue with that and say that there is a tremendous opportunity that is missed by conventional cardiology, because when we apply a functional medicine lens to it —

So if cholesterol matters, how low, and how do you get there? Dr. Ernst Schaefer is a lipidologist whose career runs through the Framingham Heart Study. In our fourth episode, I asked him the question my patients ask most: Can I lower my cholesterol without medication, or with as little as possible? Listen for four letters: ALARA.

Clip from Episode 4 — Busting the LDL Cholesterol Myth, with Dr. Ernst Schaefer

Dr. Regina Druz: Number one request that we have: can you help me lower my cholesterol without taking medications, or taking as little medication as possible? So let’s talk about it. Does LDL cholesterol lowering make a difference?

Dr. Ernst Schaefer: Yeah, it clearly does. The best analysis probably is this meta-analysis of about 49 trials done by Silverman, published in JAMA in 2016. It shows that for every 40 milligram per deciliter reduction in LDL, you get about a 23% reduction in risk with statins, and similar reductions with other cholesterol-lowering agents — higher for PCSK9s, because they lower LDL so much. But then probably the pivotal trial, the last statin placebo-controlled trial, was the JUPITER trial that Dr. Ridker did. And that trial was stopped early because it was so favorable in favor of JUPITER. And overall it was about a fifty percent reduction. But if you got your LDL to less than seventy and your CRP less than one, your risk was lowered seventy-nine percent. And we know that rosuvastatin twenty or forty can lower LDL and small dense LDL by about fifty percent.

Dr. Regina Druz: Exactly. And so what I find with patients is that, so in the trials —

Dr. Regina Druz (16:07): and I think there’s a little bit of an important distinction. So first of all, the optimal LDL in general will be less than 70. If one can achieve that optimal LDL level, that’s a great place to be. And of course the guidelines and the trials as well, they say, well, at least a 50% reduction from the baseline level, because not everyone is going to get to less than 70, and certainly not less than fifty-five. Certainly doing it through lifestyle is possible, but very hard. And in some patients, you know, medications are important. But statins are interesting, and we’re going to have a couple of episodes on statins specifically. And statins are interesting because in trials, the doses were fairly high. They were moderate, and actually, you know, rosuvastatin forty milligrams is not moderate — it’s like a moderate-to-strong intensity statin. What we find, you know, in general in terms of statin effects, is that the most LDL-lowering effect is actually at the lowest dose. That’s where you get your biggest drop, right?

Dr. Ernst Schaefer: That’s correct, that’s correct. Yeah. That’s correct.

Dr. Regina Druz: And then your subsequent dose escalation kind of gets you, you know, lower and lower drops and, unfortunately, more and more side effects. So what we do at Holistic Heart Centers, we use a concept called ALARA, which stands for as low as reasonably achievable. And we start patients at really small doses with supplement support, with an intensive insulin resistance or metabolic health program, so that we can titrate the dose if we need to. But we get to those numbers, including on LDL cholesterol and small dense LDL, not necessarily going to, you know, fairly high doses. That’s a departure, you know —

Dr. Ernst Schaefer: Yeah, I would certainly agree with you. And I would also say that every time you double the dose, you only get about another six percent reduction in LDL. And also, there are some authorities that say statins don’t really cause muscle problems. Well, I’m here to tell you they do cause muscle problems.

Dr. Ernst Schaefer (18:19): We see it every day. And coenzyme Q10 supplementation is probably helpful. I would also say that there’s a reason rosuvastatin 80 milligrams and simvastatin one hundred and sixty milligrams were discontinued in the trials and not brought forward — because they caused a lot of muscle problems in a lot of people. So I agree with Regina 100%. Start low and titrate up, and consider adding other agents like ezetimibe, because even twenty of rosuva plus ezetimibe ten will give you about a seventy percent reduction.

Dr. Regina Druz: Exactly. And that’s what we find. And, you know, I think you and I will meet sometime soon to discuss the lean hyper-responders and the role of genetics, right, in the lipid elevations and what that actually means — because it’s a certain very unique patient group that has low body mass index and a very high absorption of cholesterol from their gut. And Boston Heart Diagnostics, of course, has a proprietary test that allows us to measure that, and in combination with genetics, we’re able to identify those individuals. I also agree very much about the statin-associated muscle side effects of statins, or SAMS.

So the American College of Cardiology actually has a little app that allows us to score SAMS. And for every one of our patients, we run this scoring before the decision is made, to decide: A, will they benefit from a statin medication? And B, how much of it can we get?

Back to the remix

Dr. Regina Druz: Two quick grades on what you’ve just heard. The link between lowering LDL and fewer heart attacks is about as solid as evidence can get in cardiology. CoQ10 for statin muscle symptoms is a different story. The randomized trials are mixed, so treat it as a reasonable thing to try, not a proven fix.

Now, the other end of the spectrum. Dr. Kim Williams practices plant-based cardiology and lives it with his personal example. Here’s where he lands on statins, and where I land, which is somewhere in the middle.

Clip from Episode 13 — Vegiterranean, Anyone? Yes, Please!, with Dr. Kim Williams

Dr. Kim Williams: I can tell you that in 22 years

Dr. Kim Williams (20:44): of doing vegan cardiology — because I wasn’t going to do something that I wasn’t recommending for my patients, of course —

Dr. Regina Druz: Sure.

Dr. Kim Williams: I never had… Because I know there’s a lot of patients getting statins from cardiologists and no advice about plant-based nutrition. And then I have a whole bunch of people on the other side, the plant-based doctors, saying the statins are no good.

Dr. Regina Druz: And I’m probably somewhere in the middle because I use what’s called ALARA, right? You’re a nuclear imager just like I am. So we know ALARA — as low as reasonably achievable. So this is exactly my statin approach. Can we get it as low as reasonably achievable, considering that there’s nutrition and supplements and a lot of other interesting things that we can do?

Dr. Kim Williams: So the bottom line is that with that practice style, saying, you know, “Come on, vegan docs, statins are too good” — and fine if the person doesn’t have disease; if they have disease, they need to be on it. And on the other side, you gotta counsel about nutrition. First, you have to adopt nutrition for yourself, because the leading cause of death of cardiologists is still heart disease.

Back to the remix

Dr. Regina Druz: One note: “not one of my patients has had an event” is a clinician’s experience, not a trial. Valuable, but it’s an anecdote. Now, what happens when the risk isn’t coming from LDL at all?

[22:00] Dr. Guy Mintz on Lipoprotein(a) Strategy

Dr. Guy Mintz directs the lipoprotein apheresis program at Northwell Health. I asked him what he does for a young person with high lipoprotein(a) who otherwise looks low risk. And this is where he and I respectfully part in our opinion on statins.

Clip from Episode 25 — The Biggest Little Troublemaker: Unpacking Lipoprotein(a), with Dr. Guy Mintz

Dr. Regina Druz: And I think it’s super important — and also what you mentioned earlier — cascade testing of first-degree relatives, right? The cascade screening. Because I just saw a patient who is young, twenty-nine years old, really in great shape, fantastic shape, where one of the patient’s parents is a genetic carrier. And of course, you know, this patient unfortunately is a genetic carrier as well, but then has a lot of other, you know, pathways with genetic variability in lipid and metabolic pathways that even further increase their risk. So

Dr. Regina Druz (22:59): it’s always a combination, and I think a lot of it depends on how prepared a healthcare professional or physician is in interpreting these findings. So what is your strategy? You mentioned young patients, I mentioned young patients — what do you do for them? You know, do you give them aspirin? Do you put them on a statin? Those are typical things that guidelines advise. What is your approach to patients with lipoprotein(a) levels in that high-risk range, provided that by other parameters they are potentially in a low-risk category, right? So there’s sort of a discordance: traditional risk factors map them out as low, but this risk-enhancing feature is so powerful it kind of catapults them into an entirely different risk category. So how do you reconcile this?

Dr. Guy Mintz: Well, one is through education, and you need to spend time with your patients to educate them and explain, you know, where the risk is coming from. As I said earlier, we’re all in love with lowering the bad cholesterol, but you know, that’s 50% of the job. The job’s not over at that point. So once you recognize there are other factors that contribute to progression of disease, then you basically sit down with them and say, you know, where are we today? And if we measure the lipoprotein(a) and it’s elevated — again, the group with 125 or greater — you know, we put it into context. What are their other risk factors? Like I’m talking about the patient I saw with the 105, whatever the Lp(a) was. That was a young adult with no other risk factors. So we encourage healthy diet, exercise, you know, maintain perfect weight and so on and so forth. But now if you’re telling me we have someone with increased risk — they have hypertension, they have diabetes — then we respect Lp(a). You know, you hit on the UK Biobank studies, which show there’s a direct relationship between Lp(a) and myocardial infarction, Lp(a) and coronary disease and the other vascular beds — direct relation meaning as one increases, so does the risk of a clinical event. And in the Copenhagen General Population Study, same thing: higher Lp(a),

Dr. Guy Mintz (25:19): a greater risk of myocardial infarction. So, you know, the answer is, currently, in the year 2025, we don’t have a specific therapy for Lp(a). So once we decide we’re going to have to lower their overall cardiovascular risk with regard to Lp(a), we attack the LDL cholesterol, right? So we want to lower LDL, reduce their risk as low as we can, lower it based on our guidelines. And then depending on where we are with the patient, if it’s a high-risk patient with coronary disease, medications that we use such as PCSK9 injectables, or another injectable called inclisiran, which is a small interfering RNA molecule, can lower Lp(a) as a side benefit by 20 to 30 percent. They’re not indicated for that, but if you find a high-risk patient — now this is someone with disease that needs greater LDL lowering and they have high Lp(a) — you get a two-in-one benefit there. In terms of where we start, we lower the LDL, because LDL is clearly a specific risk factor for coronary disease, and then we’ll look at other things as well. But, you know, healthy lifestyle, proper diet, proper weight, proper exercise, and then we start with statin therapy.

Dr. Regina Druz: But statin therapy — so it’s interesting, because that’s where you and I are divergent, you know, in some ways, not always, but in some ways. Because I think up to 20% of the time statins may actually bump up the lipoprotein(a) level. And I also have not seen a universal lowering response with PCSK9s, because sometimes a patient is injected with PCSK9s and it does not seem to affect the lipoprotein(a) level much. Specifically, I had seen it in genetic carriers. So what we try to do is go one step further, because we try to assess what has been the vascular impact of this lipoprotein(a) elevation. So in some patients, we’ll get a coronary artery calcium score, although I’m aware that there is no direct relationship

Dr. Regina Druz (27:41): between lipoprotein(a) and CAC. But we actually do a lot of carotid intima-media thickness measurements, trying to establish a person’s vascular age and follow it over time. So it’s kind of a combination. Now, these newer drugs that we’re all waiting for, right, that are supposed to be lipoprotein(a)-specific — can you tell us about what they are, what has been seen so far in the studies, and what is the timeline? Because I have advised some of my patients to connect with the research sites at large universities that are offering enrollment into the phase three trials. So what is your take on this?

Dr. Guy Mintz: Right. Well, I think, currently — and we can talk a little more about it — currently the only FDA-approved treatment for elevated lipoprotein(a) is lipoprotein apheresis, and we could talk a little more about that and what that is. You know, I like what you’re doing in terms of looking for the impact of Lp(a), because you’re looking for cardiovascular effects. And for the audience, a change in carotid intima-media thickness is the very beginning of endothelial changes — the inside of the vessel changes. Carotid arteries are very big vessels, and, you know, for them to get plaque, they’ve already missed the boat. So looking for early impact is important. And calcium score — starting to see calcium in the walls of the vessels of the heart — certainly important as well. So what you’re doing is assessing cardiovascular risk. And you’re right, statins can increase the levels of Lp(a). And I give a horrible, horrible non-medical physiologic analysis of the statin effect, so please don’t boo me from reality after this. But I tell patients, if we put you on high-dose statin therapy to reduce your cardiovascular risk — and statins do more than lower LDL cholesterol; they are anti-inflammatory, they have antiproliferative effects, so there are other benefits along those lines — it’s like going to a dance. If I lower the LDL,

Dr. Guy Mintz (30:02): the lipoprotein(a) has nothing to attach to, so it’s like they’re sitting on the side waiting for a dance partner. So the levels of Lp(a) could be higher, but they’re not attaching to the LDL. So I’m waiting for the ceiling to drop on my head right now — totally physiologically incorrect, but patients can understand that, because if they do happen to measure an Lp(a) after high-dose statin therapy, it may actually increase. So you kinda have to, as you say, have a nice discussion with them. You know, I like to tell them we need to all row in the same direction, because if we’re not rowing in the same direction, the boat spins around in a circle.

Back to the remix

Dr. Regina Druz: When we recorded that, Dr. Mintz said there was no approved lipoprotein(a)-specific drug. That is still true, and this month the first one to reach an outcomes trial didn’t reduce events. So for now, the strategy you just heard is the strategy: lower other risks when you can, and look directly at the arteries.

[31:20] A 56-Year-Old’s Calcium Score and Vascular Age

Here’s what that looks like with one real patient: a 56-year-old man with a calcium score of 220, who made a decision about his medication that I did not advise.

Clip from Episode 11 — Three Men Walk Onto a Golf Course: Calcium Score Revisited

Dr. Regina Druz: I recently had a patient, and I’m going to put in exactly the numbers that the patient provided. So this patient is a 56-year-old male. The calcium score is 220, which is a fairly recent score. And up until recently, the blood pressure is fine. His cholesterol numbers were actually very good — his total cholesterol was in the 180s or so, and HDL cholesterol was about 45 or so. He was taking lipid-lowering medication, because since his late 20s he was found to have high lipid levels. And he reported that while no one had a heart attack in the family, one of the parents actually had very, very high cholesterol levels. So we’re gonna go ahead and calculate his 10-year risk. And you could see that even though his total cholesterol levels appear to be

Dr. Regina Druz (32:23): quite acceptable, the algorithm is figuring out that, being on a lipid-lowering medication, he is someone who is now in a high-risk group, right? And you could see that he’s trending into those 60s — his coronary artery age is 13 years older than his chronological age, right? Now, I want you to understand that it’s not the medication that’s doing it. Medication doesn’t have the power to influence, you know, aging of the arteries. If anything, some of the medications can help us to offset aging of the arteries; it simply factors into the continuum of risk. So this patient actually decided to stop his medications — not prescribed by me. This is just an individual who recently had an initial consult with us.

And once he stopped his medications, this is what happened. His total cholesterol went to 345. And I believe the HDL cholesterol was something like 87, but you know, let’s put it in there, right? So we’re gonna calculate his risk, right? So you could see here that the risk continues to be high, right? But it’s not that much different — a little bit different than when he was on medication. So let’s do it again. So when he was on medication — let’s actually keep the numbers consistent — he was 186 and his HDL cholesterol was 87. And very often with medications, there’s very slight changes in HDL cholesterol. Let’s give it a round number; let’s make it 90 here. And we’re gonna say that yes, he’s on lipid-lowering medication.

Let’s calculate his 10-year risk. And you could see here his 10-year risk — this is a real patient number now — while he’s on medication with a calcium score of 220, because his total cholesterol is in a reasonable range and his HDL cholesterol is in a reasonable range, actually very good and potentially genetically driven to be a little bit high, he is somewhat ahead of the curve. He’s being treated.

Dr. Regina Druz (34:50): Right now, let’s see what happens if he actually stops the medication. And this is what we saw: the total cholesterol shoots up to 345 and the HDL cholesterol stays roughly the same. You could see here that what that tells us is that the coronary artery age is now 70. Right. So where is the truth? You know, what is this person to do? How are they to make a decision? Because remember that this coronary age, it’s very useful, but it’s still a reference to a population of patients, right? What this calculator is telling us is that, taking all together the age, the gender, ethnicity, blood pressure numbers, family history, smoking or not, medication or not, as well as some basic cholesterol numbers, we could end up in different areas. So can we truly know what this person’s vascular age is? Because right now we’re simply provided with an estimate, right? And the estimate is that, taking as a composite this gentleman on a golf course, 56 years old with a score of 220 — if the numbers are exactly as you see them on the screen and he is not taking medications, that actually means that his coronary age is 70.

So this is interesting, because for many, many years this patient was treated with medication. And you had seen that on medication he actually had a very good lipid profile, right? I’m going to put it in here again: 186 he was, and we said he’s on lipid-lowering medication, and we’re going to go ahead and calculate this risk, right? And you could see that while he was being treated with medication, the medication mitigated some of the predispositions that he had, right? But what really is his vascular age? Because what I’m showing you right now

Dr. Regina Druz (37:11): is a reference estimate, right? We have gone through the exercise where we’re simply taking this person — their gender, their age, their ethnicity — plugging in all the numbers and saying, “Well, this is what those numbers mean right now,” right? What actually is his vascular age? And is there a way for us to understand the vascular age for this person — not as a reference to a broader population, but in a way that not only references them to a population of patients, but also allows us to monitor if there is a progression of atherosclerosis or regression, right? And you now know that when people say reversal, very often they imply regression and the healing of these atherosclerotic plaques.

Back to the remix

Dr. Regina Druz: His numbers moved and his estimated age moved with them. But notice what I reach for to find his true vascular age: imaging, not another calculation.

[38:00] Residual Risk and Personalized Risk Estimates

Last question. Even when a treatment is the right one, how much of your risk does it actually remove? This is from the episode where I introduced HeartWell AI.

Clip from Episode 37 — How Do You HeartWell? When Risk Scores Miss the Mark

Dr. Regina Druz: What should your cardiovascular risk trajectory be? How can you impact your cardiovascular risk trajectory? If you’re telling me, “Doc, you know, I liked all of this, but I’m gonna go right now and exercise and have a good diet and normalize my sleep and stop smoking” — this is all great. And you absolutely should do all of this. But you should also understand that there is value in additional testing, because it allows us to create not just a weather forecast, but a climate forecast for a specific area — and in this case, it’s you — and that allows us, directionally, to put you on the right path. Because how do you know how much you need to exercise? How do you know how much you need to diet? How do you know what diet you’re supposed to follow? How do you know which medications you’re supposed to take, or which supplements? If you’re still hanging your hat on those population-based metrics, you’re basically missing

Dr. Regina Druz (39:34): two-thirds of the things that could actually impact you. And this is not me saying this, this is the data saying this, because we know, for example, that even with the best medical therapies for cardiovascular disease, coronary heart disease in particular, we’re able to drive a 30% risk reduction, right? It’s a relative risk reduction. It means that if your risk is 10% in 10 years and we give you the medication, that risk will drop by a third — which is not, you know, small — so it will drop by 30%, right? So you will end up a little bit less than that, maybe five to seven percent or so, right? But you could see that the majority of the risk still has not reversed itself, right? So if you were at 10% and you now decrease to 7% or 6.5%, most of the risk is still there. And in cardiology, it’s called residual risk, right? So we know that even with the best therapies for cardiovascular and coronary heart disease, there is usually a ceiling in our relative risk reduction. It’s about 30% or so, plus or minus on either side. And so that leaves another 70% of your personal risk untouched.

And unless you’re able to understand what it is — and these days it is not that difficult, because we have these advanced biomarkers, we have genetic markers, we have imaging; they’re not for research anymore, they’re for real clinical care, and they should be used for clinical care — and we have tools such as HeartWell AI that can actually give you a personalized risk estimate.

[41:30] Three Questions to Ask About Your Risk

Back to the remix

Dr. Regina Druz: Here’s what I hope you take from this remix. Your cholesterol number matters. Medications that lower it can prevent heart attacks in the right person, at the right doses, over enough time. But the number is a guide, not the goal. Three trials in the space of a few weeks just reminded us what the whole field is actually facing. So before you start, stop, or change anything, ask three questions. What is my absolute

Dr. Regina Druz (41:53): cardiac risk? How long before this treatment actually helps me? And what did we measure to decide if I’m the right person for this medication or for this intervention? If you don’t know your answers, the HeartWell Quiz is a good place to start. It’s linked in the show notes, along with every full episode you heard today. And please don’t start or stop any medications without consulting with your physician.

I’m Dr. Regina Druz, and I am on a mission to end heart disease before it ends you and me.

Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite podcast platform. To learn more about our services, visit HolisticHeartCenters.com and subscribe to our YouTube channel. The link is in the show notes. See you next week.

Frequently Asked Questions

What is the difference between relative and absolute risk reduction?

Dr. Druz explains it with 100 untreated people and 100 treated people. If 10 untreated people have a cardiovascular event and 7 treated people do, the treatment cut events by 30% in relative terms. In absolute terms, it is 3 percentage points: 3 fewer events per 100 people. Relative numbers tend to sound large; the absolute number is the one that translates into the number needed to treat.

What did the STAREE trial show?

As Dr. Druz describes it, nearly 10,000 adults over 70 without heart disease or diabetes, with mildly elevated LDL, took atorvastatin 40 mg or placebo for almost six years. Cardiovascular events fell by 30% in relative terms — the headline — but in absolute terms about 6% of people on the statin had an event versus 8.3% on placebo. That works out to treating about 44 people for six years to prevent one event. The trial’s other primary endpoint, covering disability, dementia and death, did not move.

If Repatha lowered LDL so much in AMUNDSEN, why didn’t outcomes improve?

In AMUNDSEN, about 2,000 people having a heart attack received a Repatha (evolocumab) injection on the way to the cath lab. 82% reached an aggressive LDL goal versus 40% of those treated conventionally, yet events at 12 months did not differ. Dr. Druz points out that both groups were treated aggressively, and that a lab number can move in weeks while the biology of the arteries may take years — if it moves at all.

Is there a drug that specifically lowers lipoprotein(a)?

Not an approved one. Pelacarsen, the first lipoprotein(a)-specific drug to reach an outcomes trial (Lp(a)HORIZON), did not reduce events according to the company’s topline results; the full report is expected at the American Heart Association meeting in November. Dr. Druz notes the trial studied people who had already had events and were already aggressively treated. In the episode clip, Dr. Guy Mintz describes lipoprotein apheresis as the only FDA-approved treatment for elevated lipoprotein(a), and notes that PCSK9 drugs and inclisiran can lower it by 20–30% as a side benefit, although they are not indicated for that.

How low should LDL cholesterol go?

In the clip with Dr. Ernst Schaefer, Dr. Druz says the optimal LDL in general is below 70, and that guidelines and trials look for at least a 50% reduction from baseline because not everyone can reach that level. Both note that the largest LDL drop comes from the lowest statin dose, with each doubling adding only about 6% more. Dr. Druz describes her practice’s ALARA approach — as low as reasonably achievable — starting low, with supplement and metabolic-health support, and titrating if needed.

Do statins cause muscle problems, and does CoQ10 help?

Dr. Schaefer says statins do cause muscle problems and that coenzyme Q10 is probably helpful. In her remix commentary, Dr. Druz grades the evidence: the randomized trials on CoQ10 for statin muscle symptoms are mixed, so treat it as a reasonable thing to try, not a proven fix. She also mentions the American College of Cardiology’s tool for scoring statin-associated muscle symptoms (SAMS).

What is residual risk?

Dr. Druz explains that even the best therapies for coronary heart disease usually cap out at around a 30% relative risk reduction — so if your 10-year risk is 10%, treatment may bring it to roughly 7%, and most of the risk is still there. That remaining risk is residual risk. She points to advanced biomarkers, genetic markers and imaging, and tools such as HeartWell AI, as ways to build a personalized picture of it.

What three questions should I ask before starting, stopping or changing a heart medication?

Dr. Druz suggests: What is my absolute cardiac risk? How long before this treatment actually helps me? And what did we measure to decide I’m the right person for this medication or intervention? If you don’t know your answers, she suggests the HeartWell Quiz as a starting point.

Show Notes & Resources

About This Episode

This is a solo remix episode with Dr. Regina Druz, MD, MBA, FACC, FMCP-M — a Cornell- and Duke-trained integrative cardiologist and the founder of Holistic Heart Centers in Roslyn, New York. She reviews three cholesterol and lipoprotein(a) trials reported in 2026 and brings back clips from earlier conversations with Dr. Ernst Schaefer, a lipidologist whose career includes work with the Framingham Heart Study; Dr. Kim Williams, a plant-based cardiologist; and Dr. Guy Mintz, who directs the lipoprotein apheresis program at Northwell Health.

Episodes Featured in This Remix

Ep. 4: Busting the LDL Cholesterol Myth, with Dr. Ernst Schaefer
Ep. 11: Three Men Walk Onto a Golf Course: Calcium Score Revisited
Ep. 13: Vegiterranean, Anyone? Yes, Please! with Dr. Kim Williams
Ep. 16: Statin Overprescribing Solution (S.O.S.) Part 1
Ep. 20: Got LDL Cholesterol? Let’s Play Cholesterol Marbles!
Ep. 25: The Biggest Little Troublemaker: Unpacking Lipoprotein(a), with Dr. Guy Mintz
Ep. 37: How Do You HeartWell? When Risk Scores Miss the Mark

Trials Cited in This Episode

STAREE Trial (ESC press release)
AMUNDSEN Trial (ESC press release)
Lp(a)HORIZON topline results (Novartis, Sept 2026)

Take the Next Step

Take the HeartWell Quiz
Schedule a Discovery Call
Access Courses and Events
Get HeartWell Toolkits

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
YouTube: @reginadruzmd
Instagram: @dr.reginadruz
Podcast: Own Your Heart Health — available on Apple Podcasts, Spotify, and all major platforms

Listen & Subscribe

If you enjoyed this episode, please rate and review us on your favorite platform — it helps more people find the show.

Apple Podcasts Spotify YouTube