What to do after a Heart Attack or Stroke?

Introduction  0:01  

Welcome to the MedEvidence podcast hosted by Dr. Michael Koren and Michelle McCormick MedEvidence where we help you navigate the real truth behind medical research with both a clinical and research perspective. In this podcast, we'll have discussions with physicians that have extensive experience in patient care and research. How do you know that something works in medicine? We conduct clinical trials to see if things work. Now let's get the truth behind the data.

 

Michelle McCormick  0:33  

Welcome to MedEvidence! Truth Behind the Data. Today we're talking about what to do after a heart attack or stroke. Joining us are Dr. Albert Lopez and Dr. Michael Koren. Well, in the first segment of MedEvidence! Truth Behind the Data what to do after a heart attack or stroke, we established that people who have had either of these events a heart attack or stroke have a high risk for a repeat procedure or repeat event. We talked a lot about the team, knowing who your PCP is and your specialist, your family needs to be aware of symptoms, what's abnormal, what is normal, and if the event lasts greater than 20 minutes, that's when you really need to make that emergency medical call. Now, let's move into how to make this different and better. We touched on it briefly on the modifiable and unmodified or non-modifiable risk factors. So let's dive into that a little bit.

 

Dr. Koren 1:31  

And that's the way physicians think about things. There are things that we can change, and there are things that we cannot change, and we can only mitigate the consequences. So Dr. Lopez will give us a brief rundown on what's modifiable risk factors are and what non-modifiable risk factors.

Dr. Lopez, DO 1:45  

So Dr. Koren and I always love to talk about lipids.

 

Michelle McCormick  1:49  

I was gonna say; this is like in your wheelhouse guys.

 

Dr. Lopez, DO 1:53  

Know your lipids. I really disliked the cholesterol name, but the lipid profile, we usually focus on those are very important.

 

Dr. Koren 2:02  

And lipids, by the way, is just a word for blood flow. So blood fats, blood fats

 

Dr. Lopez, DO 2:07  

Diabetes, or pre-diabetes. And we have to remember that diabetes has four to six times higher risk factors for cardiovascular events, and even pre-diabetes has doubled the risk factor. So just because your sugar is only 100, that still doubles the risk. It's doubled from what the average Joe. So you have to be really cognizant of that and want to bring that down. overweight, obesity, both of those are really significant. Not just for heart disease, but for many chronic diseases. So that's very important. And lack of physical exercise. So movement therapy, because a lot of people are allergic to exercise. movement therapy works very well. And there are all kinds of studies we can talk about that speak to how we eat or unhealthy diets, or eating lifestyles are very important. We're a fast-paced society. And with COVID, fast food is not your best friend. It's easy, but it's not good for you. And we can talk about that and then smoking. Smoking, lighting up a cigarette or cigar because people forget cigars, but it's also tobacco in oral form is a risk factor. And vaping is not good for you. It's actually been shown to be just as bad as smoking on many levels. Blood pressure, very, very important to know your numbers, and then stress. And then the other modifier risk factor we didn't list was inflammation. Chronic inflammation is an issue and we can go into detail as you're ready.

 

Dr. Koren  3:41  

Sure. Yeah, so the modifiable risk factors are important from a clinical standpoint because we can make a difference. And there are things that we can correct. Now, this is going to blow your mind a little bit, but the relationship between the risk factor and changing the risk factor is not always straightforward. So for example, we know that there are certain risk factors that also are risk markers. Okay. So a risk marker means that there's an association. But the relationship between changing that parameter and improving things could be unclear. So for example, as we get older, our cholesterol levels actually tend to come down a little bit. But that doesn't mean that our risk comes down, right? Whereas cholesterol and lipids are one of those things that when we change them, particularly when we get them to very low levels, people just do better. They have fewer heart attacks, they have fewer strokes, and we can do it without generating side effects. So Dr. Lopez and I love to talk about that. And we'd love to talk to our patients about that because it makes a big, big difference. But what happens is sometimes people say, Oh, well, my cholesterol, when I was 30 years old, was 250 and now it's 200. So that's pretty good. I'm moving in the right direction. And meanwhile, between 30 and 50, their risk overall has gone up tremendously. So even though their cholesterol is now 200, and was 250 20 years ago, it's much more compelling to treat it now than it was when they were 30. 

 

Michelle McCormick

So the bad cholesterol, what does that mean?

 

Dr. Lopez, DO  5:18  

I think the other general sense is that people tell me oh, well, my cholesterol is always been high. And we have to remember, and it's not that bad. Well, we know that its long-term exposure to lipids is a problem. But also the intensity or how high that lipid is is also a risk factor. So even though it's only X amount x plus, if you've had that for 40 years, it's a risk factor.

 

Dr. Koren 5:45  

There's no question; it's a risk factor.

 

Dr. Lopez, DO 5:47  

You put metal in water for 30 years, even if it's mildly salivated, water, it's gonna rust, your arteries are going to rust with that high lipid level.

 

Dr. Koren  5:53  

So so again, there's some discussion about when to initiate lipid there. But again, we're talking about people that have already had an event. So the point we're really making is that once you have an event, you want to focus on those things that we can change and be extremely aggressive. And because of some things, we can't change, and because there are some things that we can't do anything about, we as physicians are going to be really, really focused and work with you on the stuff that's really modifiable.

 

Michelle McCormick 6:22  

Well, are patients, after they've had a heart attack or stroke more willing to make these modifiable changes?

 

Dr. Koren 6:30  

You get people's attention after a heart attack and stroke. So typically, they're much more amenable to interventions, particularly in the period of time right after the event.

 

Dr. Lopez, DO 6:41  

Yeah, that's so interesting that we see a huge spectrum of how people are willing to change, right? So people will say, I always ask, What's your why? Why do you want to change? Everybody has a why in their life, right? And maybe their grandchild and maybe their dog? And maybe they like to run? Maybe something? And I think you and I both have to touch on “What is your why? And usually, then you can ask them to do something. But you know, some people make paradigm changes. We've seen people go pure vegetarian, I mean, pure plant-based. And as we go, there's no way I'm doing that. I'm just not doing that. But then we'll start having a conversation. Well, how about reducing it to this much? And how about if we don't fry it, and sometimes baby steps work to get them to where we want to get them. Sometimes they can make this huge paradigm change all at once. But everybody's different and how they do that. But we're surprised sometimes that people don't make changes,

 

Dr. Koren 7:32  

Right. The other thing that's very important about modifiable risk factors is that there's a lot of interplay between them. And so for example, people that have diabetes will develop vascular stiffness over time, which will raise their blood pressure. And, in turn, certain blood pressure medications happen to help people with diabetes actually help lower their sugar levels, whereas other blood pressure medications can raise your sugar levels. So this gets really, really complicated. Why you need a risk factor expert, because there's a tremendous amount of interplay; even with cholesterol medications, there are, certain cholesterol medications that seem to have other positive effects. We use the term Pleiad trophic effects, which is the fancy medical word for saying things that are outside of just what we can easily measure. But the point being is that this gets pretty complicated. And so you'll read a bunch of things on the internet and other places about this lowers my cholesterol in this way, and this lowers it in that way. But you really want to work with an expert on these things, because you'd be surprised at how things can play out. And it'd be very, very different than what you think.

 

Michelle McCormick  8:37  

And medication can also, you know, different medications for different things can counter indicate each other and not work well together for that patient as well.

 

Dr. Koren 8:46  

So let me give a very practical example of this. So we talked about being overweight as a modifiable risk factor. Interface this with high blood pressure, diabetes, and lipids. Okay, so do you treat each of the individual things? Or do you just help people lose weight, knowing that a lot of things will improve? And, you know, we haven't had great medicines for weight loss, but that's changing pretty quickly. So sometimes, the key for some people is getting way down. And sometimes people just can't do it and have to be considered for bariatric surgery, for example. So this is where the risk factor discussion gets really pretty complicated. You need somebody that can lead you through it.

 

Dr. Lopez, DO  9:28  

Even we see this and medications in the diabetes realm, you know, if the mainstay for treating diabetes was the thought, even though your sugars are in a safer place, and that's not 100% true, right? So we've used insulins forever, but we know insulin increases weight gain, and it actually is not an anti-cardiovascular disease; it's actually pro-atherogenic. It'll make more plaque. And so the new paradigm is to move away from insulin and use some of the newer drugs that have a multiplicity of other beneficial effects. So you may use it for lowering sugar. But in may also have two new classes of drugs that lower cardiovascular events, lower stroke events, protect kidneys, and cause weight loss. But we finally have drugs that do that. And they're not just one-level drugs, and then they have risk factors. So we've, in the last 50 years, a lot has changed, and even 20 or 30 years, a lot has changed.

 

Dr. Koren 10:23  

And the funny part about this is that we've learned these things through coincidence, and by doing experiments and finding that there are unintended consequences, both good and bad when we do research, and when we look at the evidence, so Dr. Lopez was alluding to this class of drugs called SGL 2 inhibitors. And these are drugs that help the kidney get rid of the extra glucose. So they were originally developed as treatments for diabetes, they help you get rid of glucose, and they lower your blood sugar. Great. Well, the FDA, in its wisdom, said, well, let's make sure this is really safe for heart disease patients. You know, we agree, and we believe the drug company, that it lowers the glucose, but does it really help people with heart disease? So the FDA actually mandated studies with these drugs, just to show that they were safe. They weren't expecting any real big benefits on heart disease. They just want to make sure it didn't make heart disease worse. But lo and behold, we do the studies, and all of sudden, we're seeing that people who take these drugs have less congestive heart failure, they have fewer heart attacks, and their blood pressure comes down a little bit. And so there were all these unintended positive consequences that we saw for these new class of drugs that we did not see for insulin. And we did not see some of the older diabetes medications. So the point there, of course, is that you learn and you get insight from these clinical trials. And you want to work with physicians that understand this evidence because it'll get you on the right thing.

 

Dr. Lopez, DO 11:51  

Just a side cute story is as these drugs were coming out these SCL2 inhibitors, you know, it was used as a diabetes drug issue, as you mentioned. So it was endocrinologists, or diabetes specialists and primary care, you know, mainly internists, and family practice that were using them. And as data went out, then cardiologists had to go, Well, this is our drug. This is our drug. And then as soon as you know, it's our drug. I stepped up in a prevention meeting and said actually, it's an internal medicine job because we do all of this. Yeah, there you go. All you can step down. 

 

Dr. Koren  12:23  

So that's interesting, it gets back to our first segment, which talked about the fact you have to know your team. So there are some teams where the cardiologist just fixes things. And then the internist does everything else. There are other practices where the cardiologist gets much more involved, and cardiologists have to finish internal medicine training before they become cardiologists. So we have that background. But some of my colleagues have forgotten all that. And we have to trust other people that still do the day-to-day. So part of it is understanding the entire dynamics of your particular team and what each of the parties is going to be doing.

 

Dr. Lopez, DO  12:55  

And I think what we've started to lose, and I don't think you and I don't have this problem is we don't interact as easily because we expect the electronic medical record to do that. But there's nothing like calling a colleague and I've done this with Dr. Koren before. Hey, I'm worried about Mrs. Jones. She's having symptoms that I'm not comfortable with. I want to initiate this; just give me your spin on it. And do you think that's a good thing? And that's a two-minute phone call, which gives the patient this huge exponential benefit. So sometimes we have to go back to basics, you know, we forget to call we forget to interact. And your EMR may take three weeks before he sees it because he's so busy because he's not seeing the patient for two months, right? And so you know, that one phone call makes a big difference. And again, know your team, you know, know your team, and know that the team has value with each other and can interact with each other.

 

Dr. Koren  13:47  

Right. So and another example of this new class of drugs called the GLP-1 agonists. And this was originally developed, again, as a diabetes drug, with the advantage of being triggered by a meal. The problem with taking insulin is that it lowers your blood sugar all the time. And it's not triggered by a meal. Whereas a GLP-1 drug is actually triggered by a meal. So again, it was shown to be a good way of lowering blood glucose, particularly in response to people that were having elevated levels related to eating. But what we learned by doing the clinical trials is that it seems to have weight loss properties.

 

Michelle McCormick 14:20  

Yeah, I've heard this. I've heard about this. Yeah.

 

Dr. Koren 14:23  

And so they're saying that actually now approved for people that don't have diabetes for weight loss? Yeah. And they've worked pretty darn well. So turns out that this same mechanism of perhaps overeating and leading to higher glucose levels is related to this feedback loop between your gut, your liver, and your brain. And there are certain drugs that enhance that feedback loop to help people lose weight.

 

Dr. Lopez, DO 14:47  

I'm gonna even throw another curveball in here. And we started with this class of drugs and looking at arthritis on certain patients, and I'll let you talk to what our evidence we started the trial with the same a drug for diabetes you know blood sugar drop we found that they lose weight we actually found has cardiovascular benefits and then we started doing this trial on arthritis and how is that looking? The final data isn't out but it's looking

 

Dr. Koren  15:17  

and the fat in your liver goes away so oh my god. So it's very very interesting is that when you hit the right button, a lot of good things happen. So we'll talk about the right button during the next segment.

 

Michelle McCormick  15:32  

I'm your host, Michelle McCormick and we want to thank Dr. Michael Koren for his clinical and research perspective in this episode of MedEvidence! the Truth Behind the Data.

Introduction 0:01  

Welcome to the MedEvidence podcast hosted by Dr. Michael Koren and Michelle McCormick. MedEvidence where we help you navigate the truth behind medical research with both a clinical and research perspective. In this podcast, we'll have discussions with physicians that have extensive experience in patient care and research. How do you know that something works in medicine, we conduct clinical trials to see if things work. Now let's get the truth behind the data.

 Michelle McCormick  0:33  

Welcome back to MedEvidence! Truth Behind the Data. We're talking about what to do after a heart attack or stroke with Dr. Michael Koren and Dr. Albert Lopez, DO. And the last segment, gentlemen was about the stuff we can change, the way the walking the unhealthy diet. But, you know, there's a huge part of our lives that we can't change, you know, what we were born with. Let's talk quickly about the non-modifiable risk factors when it comes to our health.

 Dr. Koren 1:04  

Well, as physicians, we like to think we can change everything

 Michelle McCormick  1:07  

I know.

 Dr. Koren  1:09  

We do have some limitations, although maybe not.

 Michelle McCormick  1:14  

You can’t really change who we were born to right.

 Dr. Koren  1:18  

One of my favorite lines I tell my patients is that one of the most important things in life is to pick good parents. 

 Michelle McCormick

Fortunately, I feel like I did that for my children. 

 Dr. Koren

Well, there you go. Yeah, exactly. But it's a tough thing to do. But of course, that's a non-modifiable risk factor. Your age is a non-modifiable risk.

 Michelle McCormick 1:40  

Just a number.

Dr. Koren  1:43  

In the modern context, I identify as a 20-year-old so shouldn’t my cardiovascular risk age should be like 21.

 Michelle McCormick  1:55  

I don't know if somebody told me the other day that 50 is the new 50. So just saying. 

 Dr. Koren  2:01  

It's very confusing, but again, interesting. So, some things that are non-modifiable are typically, your family stats, your age, your gender, your ethnicity, and your weather.

 Michelle McCormick 2:19  

The weather? you got to move to a nice place.

 Dr. Koren  2:21  

Well, the reason I mentioned weather is that there's actually a lot of data showing that bad weather can lead to situational stress, and hurricanes that come into our community can raise heart attack rates. So, there's stuff like that, that we just can't control. We can try to mitigate it by being sensible, and by intervening, but we can't control the risk factor itself. But we much prefer to talk about things that we can change. And then the important thing about the things that you can change is it establishes your risk. So again, if you're high risk, because you're older, remember, age is the most important risk factor. So, a 60-year-old is much more likely to have a heart attack than a 40-year-old, and an 80-year-old is much more likely to have a heart attack than a sixty-year-old. And because of that understanding of that risk, we tend to be more aggressive as people get older. Your gender changes the way we approach things because men and women tend to have different presentations. Dr. Lopez was alluding to that. So, the typical clutter, chest choking sensation that is associated with shortness of breath and sweating that needs to build the emergency room as, as a symptom is more typical of a man. And men typically when they have their first heart attack tend to be more complete. So, the irony of that is that women may have small heart attacks to start, but they're more at risk for recurrent heart attacks because they didn't complete the job if you will when they damaged the heart the first time. So, they may have very, very different symptoms. And awareness of that is important. So again, if you're female and you've had a heart attack, your risk is actually higher than a man for recurrent heart attack. So that is not something we can change.

 Dr. Lopez, DO  4:02  

And it's something that they don't do as well.

 Dr. Koren 4:06  

So again, that's not something we can change. But it's the awareness that makes us do things a little bit differently,

 Michelle McCormick  4:11  

Right. And family history plays into that a little bit too. If your father or mother had heart disease or heart attack, your risk is higher.

 Dr. Koren 4:20  

That's general. But Dr. Lopez and I are also working on this specific thing. So, we used just to say, Okay, your family history is bad. But now we know there are very specific things that cause that family history. For example, you may have a problem called lipoprotein little a Lp(a), which is a genetically mediated dyslipidemia, or lipid problem that we couldn't do much about in the past, but now through research, we can do a whole lot for it and so that's changed very, very rapidly and continues to change as we speak. It's an example.

 Michelle McCormick  4:51  

So that's when non-modifiable and modifiable kind of even out.

 Dr. Lopez, DO 4:55  

People with familial hypercholesterolemia people that have a high family of very high cholesterol, you've got to know that because those people have a much higher risk, but we can change that risk. And we have, through research great drugs that markedly reduce that cholesterol profile, but also reduce the risk markedly as well. But you've got to know that.

 Dr. Koren  5:15  

That's a great example. What we call FH, or familial hypercholesterolemia is a relatively common genetic problem. Some of the gene incidences are probably between one and 250 and one in 500 in our community, and there are different forms of FH or familial hypercholesterolemia. But the key thing here is that those people have been exposed to high cholesterol levels throughout their lives. And they each need to have been on the drug particularly aggressively. And they're also likely going to need to use multiple drugs. It's very rare that just one drug like a statin will control a patient with FH. And typically, they need two or three even for drugs to get their cholesterol in the control. So that's an example of not being able to change the non-modifiable risk factor. But that awareness makes a huge difference in our medical approach.

 Michelle McCormick 6:10  

And then what about some of the other therapies that can be used?

 Dr. Koren  6:15  

So that this kind of jumps into specific so let me jump into specifics on lipids, since we both love talking about that. So, talk about the different classes a little bit. And some of the newer stuff, and we'll get to that, it is really exciting.

 Dr. Lopez, DO  6:27  

So, Statins have been a mainstay for a long time, but they're definitively one of the greatest risk factors lowering agents we have. I mean, if it weren't for statins, the rate of heart attacks would have been much higher, and the survivability would be much lower. As much as they're vilified and the blogosphere. Remember where your blog is coming from very often, it's just people that have had a bad effect that they think may be from that statin and may not be, but the statins are incredible. They've increased survivability markedly so then we started looking at that may not be enough. And we started looking at many other things, things like bile acids in questions, which are not used very much anymore, but they're used, and they have a benefit. This kind of blocks absorption of cholesterol, we've used things like ezetimibe, which definitively blocks in the gut wall, and you've got to be hyper absorber for this to work very well. And most people are a mix may cholesterol and absorb, but it blocks absorption of cholesterol, so it has a big benefit and lowering that level. Niacin was big 20-30 years ago, and we found that it didn't really help. It didn't show any good outcomes.

 Dr. Koren 7:38  

Once you just give them a statin it worked on statin

 Dr. Lopez, DO  7:43  

Yeah, there may be a place for it. But the side effects are marked with it. Somebody like Dr. Koren whose light-haired blonde, light skinned blue eyed, will look like a beet if he takes it. And I may be a little darker complexion may not flush. But women think it's a great revenge because then their husbands understand what menopause is.

 Michelle McCormick  8:07  

Can I get some of that?

 Dr. Koren  8:08  

But that's it's interesting. So, niacin is a very interesting product because it's quite natural to vitamin. But it actually can be much more toxic than prescription drugs, if not used correctly. I've seen people that have had incredible liver damage from overuse of niacin. So, keep in mind that even quote vitamins and natural remedies are also chemicals that can have adverse effects if they're not used properly. 

 Michelle McCormick:

Yeah, I think that's a good point.

 Dr. Lopez, DO  8:35  

Yeah. And you got to know how the compounds make because each compound is a little different. And so, it becomes into the even natural compounds have a pharmacological way how they're made, or they're produced, and they may not be all equal. And, you know, we've lost that art of knowing that in a certain season, it may be more potent, and other season it may not be, and we're not really regulating what we're harvesting and how we're making these products. they have a benefit, but we must be careful how we use them.

Dr. Koren  9:04  

Right? So, what we've learned, statins are truly remarkable. It's the most important class of drugs that's ever been developed. The easiest way to think about that for the public is that statins were introduced in the US market in 1987. And from 1987, for the next 20 years, there was a dramatic decrease in cardiovascular disease throughout the country, including here in Duval County, with a 50% reduction in cardiovascular disease deaths over about 30 years, driven in large part by statins. Obviously, things got better in the Cath lab, and the emergency rooms are doing better. 

 Dr. Lopez, DO

And so, there are other improvements, exercising, changing how 

 Dr. Koren

So, there were a lot of things that were happening, people smoking less, but the biggest contributor to that is statins. So, it's really, really quite remarkable. But even with that statins have some limitations. So, the best of the statins gets your LDL bad cholesterol down by about 50%. And a lot of people need more than that. But the other thing that we learned about statins and again from doing clinical trials and looking at the evidence is that the way they work is by up-regulating the LDL receptor. So, Dr. Lopez and I are going to have big smiles on our faces, because we can nerd out.

Michelle McCormick  10:18  

Guys are going to geek out on me now.

 Dr. Koren  10:21  

But it's important, and I think we can make it understandable. So, the LDL receptor is the part of the liver, it's on the cells and liver cells, that remove bad cholesterol from the circulation. Okay, so remember we've talked about this before, is that cholesterol in your circulation, is that what you need, it's what you're trying to get rid of. And so, your liver helps you get rid of that. And the LDL receptor is the main mechanism that is the main mechanism for doing that in the human body. And statins help your liver do that. But there are limitations and we learned that the limitations are surrounding this molecule called PSK9 and PSK9 is a counterbalance to the LDL receptor. So, when you have too much PSK9 your number of LDL receptors goes down. So, you want to get rid of PSK9, and when you take a statin even though your LDL receptors are pulling more cholesterol out, it also increases PSK9, but the beauty is that we now have drugs that target PSCk9 and if you use those drugs, in addition to statins, now you were lowering LDL cholesterol by 80%. So, it's truly remarkable what we can do.

Dr. Lopez DO 11:23  

And they have outcomes. So, it's one thing to lower it and then not there's not a benefit to physiologically, but they actually dropped the reduction of risk for stroke, heart attack, arterial peripheral arterial disease of the legs, carotid disease as well. And they reduce other factors besides just LDL cholesterol, which are all risk factors, like Lp(a) or APL or other things as well.

 Dr. Koren  11:48  

Exactly, exactly. And that's a very, very important concept. So, we know that LDL is bad when it's circulating at high levels, and we know getting rid of it is good. But what Dr. Lopez is alluding to when you look at a new drug, does it have offsetting effects that make the best go away, or that in total, it's worse than good, right? And that's why we must do clinical trials to look at that. And for the PSK9 inhibitors, as pointed out, we know they do better than bad. In fact, they're in. They're incredible, these new drugs are incredibly focused on just neutralizing the bad protein and having virtually no other effects. With our understanding of genetics and these new types of drugs, were now targeting the bad guy in exquisite ways that were not able to do previously. So, it's really just remarkable technology.

 Michelle McCormick  12:34  

It is now someone who's had a heart attack and didn't have anything, any cholesterol issues, or anything going into the heart attack episode. When they come out, are they more than likely on a statin?

 Dr. Lopez, DO 12:48  

Either way. So, we see this very often in diabetics. So, diabetics, typically in their cholesterol profile don't have high, “bad cholesterol”, LDL cholesterol. LDL may be normal or slightly elevated. So then how come a diabetic has a six times higher risk of a heart attack and stroke than statin has a benefit, even if they have normal cholesterol because it still reduces their risk by 50%? On average. So yes, it's important either way to be on the statin because it does reduce that risk markedly first or second, first event or second event, right? So, either prevention or secondary prevention, not letting it happen is that a lifetime drug? It is a lifetime job because it's not just low; its lowering is very important. As Dr. Koren said, a pleiotropic effect where it drops down inflammation, arterial inflammation, it drops down LDL itself, even to a lower level. And the question we're getting two years ago in the medical community is that it used to be that 200 or 250 was okay, for total cholesterol. You know, now we really don't look at total cholesterol so much except for ratios. The LDL now used to be well; 160 was okay, then it was 130 is okay. Now, hundreds, okay, now, it's 70. And if you look at the European data, it's 55. And we're moving to that very closely. And Dr. Koren and I both liked to see it close to 40, or 50, not even 70.

 Dr. Koren  14:12  

Just think of LDL cholesterol as something your body is getting rid of. You don't need LDL cholesterol for cells to function. Every cell in the body has the capability of making its own cholesterol, and the cholesterol in the circulation, the stuff you're trying to get rid of, since these this way to think about it. But again, bringing this back to our first segment. In our original point, if you've had a heart attack and a stroke, and you're not on a statin, there's a problem. Now, either you may be allergic to it, or you may have some which is very rare. By the way, almost no one's allergic to statins, but there's you should question that. So, if you've had a heart attack and stroke the first thing is are your lipids optimally controlled now, you may not have an LDL problem. There are other lipid problems as we alluded to that have different solutions. So, there is this type of dyslipidemia that has very low-end HDL cholesterol and high triglycerides, which gets treated a little bit differently. But still, a lot of those people are going to be on a statin as well. So, you should be dealing with a team that is very focused on your lipid situation if you've had a heart attack or stroke. And if you're not on a lipid-altering agent after that, I would raise questions. I think we probably agree with that.

 Dr. Lopez, DO 15:19  

Oh,  definitely. And I think we have a bigger armamentarium. Now we have more, more drugs to treat, even if, and I agree with you. I think the statin intolerance or not tolerability of using a statin is much lower than what's reported because a lot of people just won't take it, they've blocked their mind, or physicians just get tired and just say, well, whatever, I'm just not using it. And very often, a good example is I have a lady who lives on an acre and a half. She has a lot of trees on, and it was very hot here in Jacksonville, and she sat most of the summer while the fall came and the leaves are falling, and she decides to rake an acre and a half in one day. And of course, the muscle aches were due to the statin not because she raked for eight hours. And she had been sitting for five months. I mean, heck, I exercise all the time. And I would be achy for raking eight hours. Yeah, you know. And so of course it was a statin. So, you know, how do you approach this, this is the novel idea of the art of medicine. I took her off for two weeks, let this muscle aches resolve, and the data does show that 80% of the people that come off a statin and reinstitute it are tolerant of it. And if they're not, then there's some data that says maybe we can use COQ 10. That’s a whole other story. And she was so happy because she knew she was protected.

 Dr. Koren  16:36  

So, this is the difference between the internal medicine approach and the cardiology approach. He gave her two weeks off a statin, and I would have hired a yard service.

 Michelle McCormick  16:45  

We are talking about MedEvidence truth behind the data what to do after a heart attack or stroke. Dr. Albert Lopez and Dr. Michael Koren. Gentlemen, we've talked a lot. And I just want to tell you this Dr. Koren, your team you like to study the research of research, which ways of improving site performance recruitment and operational efficiencies, right? So, what are some of the specifics and research that we can talk about with this topic today?

 Dr. Koren 17:13  

Sure. Well, this is what I do day to day guys looking at research studies. And when we talk about the research of research, its ways of doing research more efficiently. So, this podcast will be an example. So, we're, of course, one of our motivations is to get the word out about some of the great research that's happening in our communities. And there's been a change in the way research has been done over the last 30 years. 30 years ago, most of the research was done in big academic medical centers. But now more and more research is moving out to community-based settings. And we're part of that trend. So, when we talk about the research of research, that's telling people about what is available in the community. And so, we're excited about that. And great physicians like Dr. Lopez, who is, you know, works day to day taking care of patients and doing his thing can also be part of research, because of the infrastructure and the resources that we have at the research centers here in Northeast Florida and other places around the state. So that's the research of research.

 Dr. Lopez, DO  18:11  

Did you know how I got involved with Dr. Koren? 

 Michelle McCormick

I do not. 

 Dr. Lopez, DO

So, you know, we've known each other for a long time. And every time I went to a talk Dr. Koren, he says, you know, you really, really need to work with me. And you know, I was in the trenches. Yeah, I don't have time. I can't do it. I can't do it. For 20 years he hounded. And so finally, at one point, I sat down with my list bucket list and said, What have you always wanted to do? And I said, I really want to be instrumental and do new research and new data. And because I read all the time, it'd be fun if I could do it, but I'm not in a university setting. So, my chances are zero, and then a light bulb went up in my head and said, let me talk to Dr. Koren. And it's been big, it's only about a fifth of my week. And it encompasses about 80% of my joy because it's exciting. It's great nerdism. And I get to do a lot of fun things and really think you know and help people. But I want you to tell, talk about the level of research we do. You know, Dr. Koren has been published several times, as you've mentioned, but recently he just published an international study on LP(a) a, which is one of my bugaboos, and we've known about this little protein for 20 years, we've had nothing that really, we had things that lowered it like vitamin C, but it showed no benefit. So why take something if it doesn't have a benefit in reducing risk, right, and doesn't reduce events, but he has a paper International Paper that would help reduce LP(a) a 90%, which is incredible, you know because this is a modifiable risk factor in 20% of the general population. So, imagine if we can reduce cardiovascular disease by 20%. Wow, internationally, that's an incredible thought. And you know, Dr. Koren is part of that. He won't tell you that, but I'll tell you that because I'm proud to be on this team.

 Michelle McCormick  20:01  

Well, that’s why he's in the lab coat, and you're in the suit.

 Dr. Koren  20:08  

I appreciate those kind words; I thought the only one that extra read my work was my mom. I guess there are a couple of other people out there that do read it. Even my mom couldn't get through my paper. But it is cool I agree that these are things that we couldn't modify at all. And now we have these new products that understand the genetics of how these proteins are being developed and can block them to degrees that were unimaginable just five years ago. So, it's really, exciting.

 Dr. Lopez, DO  20:39  

And let me just take a little 30 seconds because, you know, we talked everybody's know something about messenger RNA because of the vaccines, but you have DNA, which is what we are. And then messenger RNA comes up. And it's kind of like the guy who reads the template, right, who reads the architectural plans and then starts manufacturing. Well, this drug snipers, one little protein, it doesn't affect anything else on it, it stops one protein that makes this compound, which is very dangerous, it, it's pro clotting, it looks like clotting factor. It causes systemic inflammation, arterial inflammation, and increases the risk of aortic stenosis at a very early age, and it doubles and triples the risk of cardiovascular disease, arterial diseases, legs, and carotid disease, even people with normal cholesterol, which is kind of crazy. And it may have had a function in the past. But irrespective of that, it doesn't really have a good function in modern society. But imagine that we're in sci-fi times, we're in Star Trek times wherein, you know, Guardians of the Galaxy times we're doing incredible technology today. And it's so cool to be part of that.

 Dr. Koren  21:50  

Yeah. And the other thing that's cool is that people who are listening to this and people in our community can be part of it right now. We're enrolling in programs that involve using these products. So, these products have been developed at our center starting first in human studies. We're doing first and human studies as we speak on these new products that are targeting lipid, Lp(a). And we also have phase three products, projects where people know that the drug has been used and already in, you know, hundreds or 1000 people. And they're part of the next wave to show that it can work in 10s of 1000s of people, and ultimately be part of the process of getting these things on the market. It's funny, I had an interesting conversation with a patient just yesterday. And he was involved in the studies with PCSK9 went, which is one of the PK inhibitors. And I happened to be the second author of the first phase two study for that particular product. And he was in that study. And he didn't really have awareness of that. He knew that he was in a research study. And he knew that it works really, really well. But he didn't really know that he had an integral part in developing that drug. So, it didn't quite connect with him. And I mentioned that said, you know, you're one of the reasons why that's you're able to take it now. And he said, Wow, I never thought about that. Yeah. So, it's actually an important motivation for people, you can really make a difference you can be it's a legacy for you. It's a legacy for your family. And it's how you impact the world. So, participating in clinical research is, you know, really a joy for me. It's an honor, and it's anything for our patients. And I'd love to get patients interested in involved in it.

 Michelle McCormick  23:27  

Yeah, I mean, and because of that clinical trial research is how the vaccine the COVID vaccine was able to be pushed as quickly as it was to everyone.

 Dr.  Koren 23:35  

Here in Northeast Florida, we had a huge impact on that we had 1500 people get investigational vaccines before the rest of the world had access to them. So, it's really a neat part of promoting clinical research here in our community.

Michelle McCormick 23:48  

Yeah. And what about technology? You mentioned the technology. What's the future looking like?

 Dr. Koren 23:54  

Some of the specifics. So, we talked about LP(a). Let's talk,  a little bit about oxidized LDL? 

 Dr. Lopez, DO  24:00  

Sure, it's another area I've been looking at for over 20 years. And, you know, the story for me was that having a patient that had recurrent stents put in, heart attacks, mini stroke strokes, and I got very frustrated so I started looking at different things in his lipid profile that would affect it and looking at these advanced lipids, I found certain factors that we found that he had less dense going on after about two years of changing therapy because it allowed me to modify therapy according to what were his risk factors. And then the technology came out to look at oxidized LDL and so if you imagine LDL is just a substrate a piece of metal, right? And if you think of your arterial wall like volcano lava just has to be activated in order for that volcano to erupt. A piece of metal has to be rusted in order to you know, oxidized to become rusted. So, if you think of our arterial wall as rust being rusted it before it ruptures, oxidized LDL is the product of this bad cholesterol being activated or oxidized. And now it's a risk factor for cardiovascular disease. So, we've seen people with high LDL or moderate LDL, and they don't have events. But if it's oxidized, they're making plaque period. So, you can look at very early years ahead if you're looking for oxidized LDL. So how do you prevent one of my big mottos is, you know, we can throw all kinds of therapies will not stop cardiovascular disease until we really focus on prevention. And this is a good way of looking at prevention. We're doing it way, way upstream, right? Not after the event happens, like we're talking about, but we now have drugs that can do that,  and look at oxidized LDL.

 Dr. Koren  25:45  

So again, oxidized LDL is an LDL molecule, which is a combination of fat and protein that circulates into the way our body gets rid of the extra cholesterol and the extra fat. And when it's oxidized as a chemical change that's occurred, that makes it more dangerous. But there's actually this interesting correlation between oxidized LDL and lipid protein Lp(a), which is that our LDL receptors have a hard time getting rid of these things. So, as I mentioned, the LDL receptor is the main way that our body gets rid of bad cholesterol. But if it's oxidized, or if it's in the form of lipoproteins delay, or LDL receptors don't get rid of it very well. And so, it lingers. And when it lingers in the other parts of our body that try to get rid of it, the part of our body that tries to get rid of oxidized LDL are called macrophages. And that leads to inflammation and other problems, which ultimately creates plaques in the arteries. So, it's nasty.

 Michelle McCormick 26:39  

Yeah, yeah. And it's just building up and building up.

 Dr. Koren 26:43  

But the good news is that with technology, we can now come up with therapies that target oxidized LDL specifically. And of course, as we speak, we're doing a clinical trial. We're actually working with the TIMI Group at Harvard on this particular trial.

 Dr. Lopez, DO

That's an instrumental study from 30 years ago. The original TIMI study was initiated 30 years ago, but we've kind of moved this study along over 30 years and shown improvement upon improvement and improvement.

 Michelle McCormick  27:15  

That's interesting. 

 Dr. Koren

Yeah. Well, it's a personal thing, because actually, the reason I’m a cardiologist is because of TIMI. I actually got to see the first TIMI trials. I don't want to say what year it was because of 

 Michelle McCormick

just a number, just a number.

 Dr. Lopez, DO  27:29  

I heard you tried to change your middle name to Timmy. 

 Michelle McCormick

Was Timmy a guy or? 

 Dr. Lopez, DO

We’re not going there. Okay.

 Dr. Koren  27:40  

Well, we can get to that in a second. But before we get to the acronym. It’s an acronym for a group out of Harvard, that was actually started by Dr. Eugene Braunwald. He’s a very famous cardiologist and actually one of my mentors when I was in medical school. And it stands for, It's to limit Myocardial Infarction, is basically what it is, and is what stands for myocardial infarction being the word for heart attack. But, we are working with that group. And they're up to their 80th trial or something. And it's called TIMI 1 versus TIMI 80 because it’s a series of trials. But nonetheless, we actually have a product that targets oxidized LDL. And we're looking at it specifically for people that have had a previous heart attack. And we think that this may be a really fascinating way to limit the damage from LDL, particularly, as Dr. Lopez mentioned, our ability to lower LDL is really pretty robust right now. But it's much more difficult to get to these bad actors of LP(a)and oxidized LDL. And now we can.

 Dr. Lopez, DO 28:43  

So, it's interesting, you know, no matter what you do, you can't lower Lp(a) literally, it's there. So, you can exercise, it doesn't change it. You can be on a statin; it doesn't make it better. You can eat grass; it's not going to change it.

 Michelle McCormick  28:55  

How do you know you have it?

 Dr. Lopez, DO  28:57  

You have to get tested. 

 Michelle McCormick

Okay, 

 Dr. Lopez

There’s a big push

 Dr. Koren 29:00  

but I thought CBD can do everything.

 Dr. Lopez, DO  29:02  

Or you just don't care.

 Dr. Koren  29:05  

But you mentioned eating grass,

 Dr. Lopez, DO 29:06  

But you know, the young adults don't know who your Gibbons is anymore.

 Dr. Koren  29:13  

That's true.

 Michelle McCormick  29:14  

I’m sorry. I didn't mean to interrupt. I was just like; how do you even know you have Lp(a)

 Dr. Koren

Get tested

 Dr. Lopez, DO 29:18  

We think everybody has a lab test and everybody should be tested for Lp(a) literally, especially in certain populations. People that have early heart disease, a family history, or themselves have early heart disease, carotid disease, stroke, arterial disease of their legs, or have aortic stenosis should be tested, but there's a push among certain people that think everybody should be tested. And if everybody should be tested, when do you test somebody, when they're 10? Or do you test them when they're 20? Do you test them when they're 60? That's been an ongoing argument. So, there are three camps those should be everybody should be tested, those camps only if you have risk factors, and those camps that said, Well, yes, we should be tested but done at adolescence to pre-adolescent age. So yeah, it's very interesting about that. But there are things that will change oxidized LDL. So, we know that pre-diabetics and diabetics have a higher level of oxidized LDL, we know exercise drops, ox LDL, we know eating clean foods, non-processed foods, non-high saturated fat and fatty foods, good fats versus bad fats, bad fatty foods, a lot of fried foods, a lot of people with a lot of foods with

 Dr. Koren

Bacon, want to raise you oxLDL, eat bacon

 Dr. Lopez, DO

As much as I like bacon what made me stop eating bacon was a) I’m cheap and it made me mad that 80% of what I was eating was fat and I couldn’t do anything with it. The second was the cancer risk that drove me crazy, and the heart disease risk is awful.

 Dr. Koren

It’s the chemical used to process it

 Dr. Lopez, DO

So, there are things that we can do. Sometimes it’s not enough to do the natural ways exercise, eat a cleaner lifestyle, eating less sugar. Sometimes you need something to drop it more especially if you have had an event.

 Dr. Koren

To wrap up, getting back to our research and our first point about people who have had a heart attack or stroke, there are many ways we can help them. Literally, we just scratched the surface with the last hour. What’s important to know is you work with your team, there are ways to reduce your risk and research is an option because there are a lot of opportunities to approach that were not approachable years ago. There are many ways to put yourself in a better position to reduce your risks. We have lipid studies, and smoking studies.

 Dr. Lopez, DO

ENCORE has been a hidden gem in our community. We worked with several drugs that are on the market today.

 Dr. Koren

It’s not just drugs, we are working on an app to help with heart failure.

 Michelle McCormick

 I'm your host, Michelle McCormick and we want to thank Dr. Michael Koren for his clinical and research perspective in this episode of MedEvidence! the Truth Behind the Data.