The Heart Attack and Stroke Risk Hidden in Plain Sight

Dr. Michael Koren sits down with a clinical trial participant named Walt to talk about lipoprotein(a), also called Lp(a). At a community health event, Walt discovered he had hight levels of Lp(a), which puts him at an increased risk of heart attack and stroke. Walt asks what Lp(a) is, how it causes damage, and how the investigational clinical trial medications work. The duo then move through how Walt has felt through the clinical trial process and the enrollment demographics in a clinical trial.

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Have a question for Dr. Koren? Email him at askDrKoren@MedEvidence.com

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Transcript

Welcome And Today’s Goal

Announcer 0:00

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts, hosted by cardiologist and top medical researcher, Dr. Michael Koren.

Dr. Michael Koren 0:11

Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence! And I'm going to do my favorite thing today, which is to talk to a patient. And I'm fortunate to have Walt here with me, who is actually currently involved in a clinical research trial looking at the problem of lipoprotein( a). So our goal today is to explain what lipoprotein(a) is and what the patient experience is when he or she participates in a study like this. So Walt, welcome to Med Evidence!

Walt 0:41

Thank you, Doc.

Dr. Michael Koren 0:42

We really appreciate you coming.

Walt 0:43

Oh, thank you.

Meet Walt And His Story

Dr. Michael Koren 0:44

So again, we're very mindful about confidentiality. You've agreed to talk with me, and I'm going to call you, Walt. Just to keep it confidential in terms of whatever details you want to share with people. But if you're okay with it, just give the audience a little bit of perspective about who you are as a person.

Walt 1:00

I'm Walt. I live in Jacksonville, Florida. I'm retired. I had a career in research as well as computer science and software engineering. And I'm here enjoying the Florida weather. That's a little bit about me.

Dr. Michael Koren 1:15

All right. Did you grow up in Jacksonville or you you transplanted here?

Walt 1:18

I'm a transplant. I did not grow up in Jacksonville.

Dr. Michael Koren 1:21

Where'd you grow up?

Walt 1:22

I grew up in Montgomery, Alabama.

Dr. Michael Koren 1:24

Very nice. Very nice. So you're involved in a research program as we speak that's looking at the problem of lipoprotein(a). 

Walt 1:31

Correct.

Dr. Michael Koren 1:32

So how how did you learn about this? How'd you find out that you had this problem?

Walt 1:36

So my sister's a physician. She had a health fair at her church. And so she was testing people for, you know, all of the things blood pressure, diabetes, et cetera, et cetera. And one of the things she tested for was the lipoprotein( a), the little Lp(a). My wife and I attended the health fair and both got tested. My wife came back low, my numbers were high. And she told me about this clinical trial that you know they were doing that I would be a candidate for and asked me to look into it. So I decided to do it.

Dr. Michael Koren 2:09

Interesting. Had you heard about lipoprotein(a) before this experience?

Walt 2:13

No, I had not.

Dr. Michael Koren 2:14

So this was an educational event that got you interested in the problem that led you to become involved in clinical trial.

Walt 2:21

Yes.

Dr. Michael Koren 2:21

Very cool. Very cool. So do you feel like you know something about lipoprotein(a) now that you're involved in the research program?

What Lp(a) Is And Why It’s Different

Walt 2:28

Yeah, I do. I really do. I didn't understand and or realize the impact it would have in terms of stroke and the cause of stroke. You know, I I I definitely keep my normal cholesterol, my LDL and my HDL, I monitor those on a regular basis because I'm diabetic. And those were were fine. But once my sister explained to me about the Lp(a) and how, you know, most blood tests don't test for that, and that could be a problem.

Dr. Michael Koren 2:55

Exactly. So for the for the benefit of our audience, I'm going to explain a couple of things about a cholesterol profile. So standard cholesterol profile looks at the total cholesterol, and cholesterol is a fatty substance which doesn't particularly mix well in a liquid environment of your blood. So your body has to make something called lipoproteins so that the fat part and the protein part can come together and circulate in the blood. Every cell in our body makes cholesterol. And the stuff in our bloodstream is by and large the stuff that our body's trying to get rid of. So we get rid of it in different ways, but the primary way of getting rid of LDL cholesterol is through the liver, something called the LDL receptor. And we have a lot of great medicines, including statin drugs, that help the body get rid of the LDL cholesterol. But there's a form of LDL cholesterol called lipoprotein(a), which is an LDL molecule with an extra chain around it. It's called an apolipoprotein(a). And that extra chain makes it more difficult for your body to get rid of that molecule. So whereas when we use a statin drug, we can get the LDL cholesterol down by about 50%. But statins have virtually zero impact on lipoprotein(a). In fact, currently there's no approved drugs for lipoprotein(a). And some of the drugs that are on the market have a little bit of an effect on Lp(a). So for example, if you use niacin at high doses, it'll bring the Lp(a) down a little bit. If you use PCSK9 inhibitors like Repatha or Praluent, that'll bring Lp(a) down a little bit. Then by and large, those are small drops, maybe 20%, 25% on a good day. But in research over the last five years, a number of molecules, a number of treatments have been pushed forward through clinical research that now lower Lp(a) by 95% or more.

Walt 4:53

Wow.

Dr. Michael Koren 4:53

It's incredible.

Walt 4:54

It is.

Dr. Michael Koren 4:55

Okay. So you haven't heard much about Lp(a) in the past because we didn't have any way to treat it. And now we are on the verge of having a group of products that will actually effectively treat Lp(a) and bring it down from very high levels.

Walt 5:10

Okay.

Dr. Michael Koren 5:11

So we know we have products that bring it down, bring Lp( a) down from very high levels. What we don't know yet is whether or not bringing those levels down will reduce heart attacks and strokes. And that's research that we're doing right now that you're part of.

Walt 5:26

That's fantastic.

Dr. Michael Koren 5:27

Yeah.

Walt 5:27

Yeah.

Dr. Michael Koren 5:28

Now Lp(a) is an interesting molecule because it runs in families. And you either have the disease or you don't have the disease for at some level. So certain families, typically families that have a lot of members who have had a heart attack and stroke at an early age, tend to have higher Lp(a) levels. So let me ask you that. Do you have a family history of people who have had a heart attack or stroke, say before the age of 60 or 65?

Walt 5:53

No.

Dr. Michael Koren 5:55

Oh, okay. So interesting. So you found out that you had a high Lp(a) level. Do you remember how high it was during the screening?

Walt 6:01

No, I don't.

Dr. Michael Koren 6:02

Well, I happened to look at your chart before you came in and your Lp(a) level was 200 nanomoles, which is not all that good. And it puts you at higher risk. But it's interesting that you don't have a personal family history. So we're learning more and more about Lp(a), and we think maybe there are certain types of Lp(a) that are more dangerous than others, but we don't know that right now.

Walt 6:24

I see.

Dr. Michael Koren 6:24

So what we know is that when you have a level of 200 and it should be less than 75, your risk is higher than it should be.

Walt 6:32

Wow.

Dr. Michael Koren 6:33

And the studies that we're doing are trying to reduce that risk.

Walt 6:37

Okay.

Dr. Michael Koren 6:37

Okay.

Walt 6:38

Mm-hmm.

Dr. Michael Koren 6:39

So thank you for being part of the studies, for one. And I have a few questions about that out of curiosity.

Walt 6:44

Sure.

Dr. Michael Koren 6:45

You're in a study, we don't know whether or not you're on active medication or placebo, which is often the case in many of the trials.

Walt 6:51

Okay.

Dr. Michael Koren 6:51

And uh so I won't give any information about that, but I will say is that you're part of a group that will get information before the general public. So for example, as we learn more things about lipoprotein( a), we will share these things with you.

Walt 7:05

Okay.

Dr. Michael Koren 7:06

And often the research changes based on information that we get from the field. And that's part of this incredible group of people we have all around the world that are studying this with us.

Walt 7:16

Okay.

Dr. Michael Koren 7:17

And they're literally centers every place on the planet that are looking at patients like you. And as information comes in, we share that. So if there are any safety issues that come up, we share that immediately. If there's something showing that there's a benefit in one way or another, we'll tend to share that with you.

Walt 7:32

Okay.

Dr. Michael Koren 7:33

But we usually don't get the big results until a major medical meeting when scientists such as myself will present information to other scientists and say, hey, this is what we learned when we did this program.

Walt 7:47

Okay.

Dr. Michael Koren 7:48

And we will be representing you during those discussions.

Walt 7:51

Oh, good.

Dr. Michael Koren 7:52

It's a pretty cool thing.

Walt 7:53

It is. It is.

What Trial Participation Is Like

Dr. Michael Koren 7:54

So what was your experience? Did we so far meet expectations or was it different than what you thought it would be?

Walt 8:01

Since I've never done a clinical trial before, everything was all new to me. But so far I've been uh pleased.

Dr. Michael Koren 8:07

Excellent.

Walt 8:08

Um, you know, no issues. You know, everything's been going uh as you said, it would, you know, I meet periodically with my clinical

Dr. Michael Koren 8:16

Coordinator

Walt 8:17

Coordinator.

Dr. Michael Koren 8:18

And she's terrific.

Walt 8:20

And she's terrific. Shout out to her. And so so everything's going well. Beautiful. So would you do a study like this again when you're finished with this experience? Yeah, I would consider it. Yeah, I would consider it because uh so far the the experience has been pleasant.

Dr. Michael Koren 8:33

Excellent, excellent.

Walt 8:34

Yeah.

Dr. Michael Koren 8:34

And obviously we'll get some information down the road in terms of what you were assigned, were you assigned to the active drug versus placebo? But more importantly, you'll get a lot of input in terms of your lifestyle and how to maximize that. And then when the study gets to its conclusion, we will sit down with you and talk to you about what next steps might look like.

Walt 8:54

Oh, okay. All right.

Dr. Michael Koren 8:55

And so in many cases, we will have access to the product for a period of time for many of our study patients. We certainly can't guarantee that, but in many cases that's the case. And depending upon the outcomes, we'll again go over things in much greater detail and sort of plot out what next steps would look like for you to try to reduce your risk of heart attack and stroke in the future.

Walt 9:14

Okay. All right. That sounds good.

Dr. Michael Koren 9:16

Any questions that you want to address to me at this point?

How Gene Silencing Drugs Work

Walt 9:20

Yes. So so the drug that we are doing the clinical trial on, how does it how does it work?

Dr. Michael Koren 9:27

Sure. Well, every every product that we look at have different mechanisms of action.

Walt 9:33

Okay.

Dr. Michael Koren 9:33

And some of them in this space have used a mechanism called small interfering RNA.

Walt 9:41

Okay.

Dr. Michael Koren 9:41

And what that basically does is it silences the gene that's responsible for developing the Lp(a) molecule. So if you go back to your old biology classes in high school or college, if you remember, you have DNA, right? And then DNA turns into RNA through a process that we call transcription and translation. And then ultimately the information from the DNA gets turned into a protein. So in the research that we're doing now, we're blocking that step at a level that's called the risk or the RNA-induced silencing complex.

Walt 10:18

Ah, okay.

Dr. Michael Koren 10:19

Okay, so that's a little like fancy language. But really, what it is is that we've learned that our bodies have the ability to take gene products that may not be so good for us and silence those genes. And we actually learned about that through viruses. So when you think about it, when a virus gets into our body, that's foreign DNA or RNA that's trying to create havoc. So our body has to have a mechanism to deal with that. And the mechanism that we use to deal with that is called RNA silencing. Or in some cases, if it's a DNA virus, it's when the DNA is transcribed. And the concept there is in our own bodies, if there is some material that we don't want expressed, we have an intrinsic ability to do that. And the drugs that we're using now are designed to tell our body what that bad gene is.

Walt 11:10

Oh, okay.

Dr. Michael Koren 11:10

And then silence it.

Walt 11:12

Okay. That's pretty cool.

Dr. Michael Koren 11:13

It's damn cool. It's super cool. Anyhow, so and not everybody, not all of our patients once get onto the details. Obviously, you have a scientific background, so you can kind of dig it. But concept here is that every every study has a different type of mechanism that we're studying. And at the end of the day, we're looking at the safety and the effectiveness of the products.

Walt 11:34

Okay.

Dr. Michael Koren 11:34

And then hoping our patients get a great experience. And and number one is education.

Walt 11:38

Yes.

Dr. Michael Koren 11:38

But patients get paid a little bit for what they do, which is a nice thing. You know, that can't hurt, of course.

Walt 11:43

Right.

Family Testing And Trial Diversity

Dr. Michael Koren 11:43

And also you're going to be sort of on the cutting edge. So in something like Lp(a), you can also inform your family members.

Walt 11:50

Yes.

Dr. Michael Koren 11:51

So as we discussed, this is a problem that runs in families.

Walt 11:54

Right.

Dr. Michael Koren 11:55

So if you have brothers and sisters, they have a 50-50 shot of having this problem.

Walt 11:58

Right.

Dr. Michael Koren 11:59

Your kids have a 50-50 shot of having this problem, unless your wife or your partner has it, and then the odds go up, of course, from that.

Walt 12:06

How How is that inherited? I mean, in the some sense it's genetic based, it has to be passed down genetically, right?

Dr. Michael Koren 12:14

It's called autosomal dominance. So mean that you have a 50% chance of giving it to your your kids.

Walt 12:21

Okay. So if if one partner it is not gender-specific, like female.

Dr. Michael Koren 12:27

No, there are there are some genetic conditions that are sex-linked, but this one is not a sex-linked condition.

Walt 12:32

Okay. All right. Interesting.

Dr. Michael Koren 12:33

Yeah. So that's what we do in clinical research, is we share these little nuggets of information.

Walt 12:38

That's very, that's very good, Doc.

Dr. Michael Koren 12:40

I appreciate that.

Walt 12:40

I appreciate that.

Dr. Michael Koren 12:41

My pleasure.

Walt 12:42

Yeah.

Dr. Michael Koren 12:42

Any other questions or anything else you want to run by me?

Walt 12:45

So in in terms of your your your the demographics of your samples, right? What's the ethnicity makeup? Because a lot of clinical trials tend to be skewed toward, you know, Caucasian, European-based sample size.

Dr. Michael Koren 12:59

Sure.

Walt 13:00

So how how does that work with these clinical trials?

Dr. Michael Koren 13:02

That's a great question. Thank you for asking that.

Walt 13:04

Okay.

Dr. Michael Koren 13:04

So diversity is important in clinical research. There's a lot of elements of diversity, but uh racial and ethnic diversity is one of the things that we look at.

Walt 13:13

Okay.

Dr. Michael Koren 13:13

And we're very proud of the fact that here in our center in Northeast Florida, that we have patient population that kind of reflects our community. So Jacksonville is about 25% African American, and our studies typically have that demographic.

Walt 13:28

Okay.

Dr. Michael Koren 13:28

Because we you know specifically reach out to different communities to make sure that everybody's represented.

Walt 13:32

Fantastic.

Dr. Michael Koren 13:33

But there are some illnesses that are more or less prominent in different patient populations. So for example, we're doing studies now as we speak in hypertension or high blood pressure, which is a bigger problem for the African-American community than others.

Walt 13:47

My mother had it.

Dr. Michael Koren 13:48

Yeah, there you go. So we actually do more outreach for those type of projects in the African-American community.

Walt 13:54

Okay.

Dr. Michael Koren 13:54

So there so in this particular study, I know we have pretty balanced representation across race and ethnicity, but in some studies it may be skewed one way or another, depending upon the way the illness affects people in different communities.

Walt 14:08

Oh, okay. All right. Fair. That's good.

Dr. Michael Koren 14:10

Yeah. Great question. Really good question. Thank you for asking.

Walt 14:13

You're welcome.

Dr. Michael Koren 14:14

So again, the take-home message is that it's kind of a pleasant experience to be in clinical research.

Walt 14:19

It is.

Dr. Michael Koren 14:19

In something like Lp(a), where there are no standard treatments, it gives you some hope.

Walt 14:23

Yes. Absolutely.

Dr. Michael Koren 14:25

And it gives you education and knowledge that you can share with family and friends and hopefully move science forward collectively.

Hope, Education, And Closing

Walt 14:32

Absolutely. Absolutely.

Dr. Michael Koren 14:34

Well, thank you so much for being part of MedEvidence. We truly appreciate it.

Walt 14:40

I hope I can help.

Dr. Michael Koren 14:41

You certainly have. Thank you.

Walt 14:42

Thank you.

Announcer 14:43

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