Lipoprotein a with Dr. Steven Nissen

Dr Steven Nissen and Dr Thomas Nero discuss the importance of Lipoprotein a -aka Lp(a)- and its clinical importance as a special type of LDL cholesterol which dramatically increases your cardiovascular risk.  They also covers why it important to get it tested at least once and what you can do to lower your risk of heart attack if you have it.    If you enjoy this episode you may want to take a listen to the research oriented version of this topic at FUTURE PULSE CARDIOLOGY.

Transcript

PATIENT PULSE 

Dr Steven Nissen and Dr Thomas Nero discuss Lipoprotein a

Good morning and welcome to Patient Pulse. I'm Dr. Tom Nero. Today,  we are with Dr. Stephen Nissen. Dr. Nissen is the chief academic officer at the Cleveland Clinic and has been the,  clinical trial lead for a number of Lp(a) trials and is probably one of the smartest cardiologists in the entire world if you ask me.

 I'm really pleased to have him with us today to discuss lipoprotein little a and its effect on,  the development of ischemic coronary artery disease. Thanks for joining us.

Well, it's a pleasure to be with you.

So we're going to jump right in and say the first question  is what the hell is lipoprotein little a and why should we care

Yeah. , it's a special kind of a cholesterol particle, , that like,  low density or LDL cholesterol that everybody knows about. And most people hopefully know what their level is.  Much fewer people know what their lipoprotein A level is, but it is substantially , more likely to provoke atherosclerotic cardiovascular disease than LDL.

It is more atherogenic, if you will, than LDL cholesterol, and it is also promotes thrombosis and  cardiovascular disease. Coronary disease particularly is an atherothrombotic disease, atherosclerosis  and thrombosis or clotting.  And this particle promotes both.  

With lp little a how much over the ldl levels does this increase your risk 

It depends on how high your level is. There are two unit systems, milligrams per deciliter and nanomoles per liter. And they're very different. Uh, but if you use milligrams per deciliter, you know, once you start to get above 70 milligrams per deciliter, risk goes up. And the higher , your level is, the higher the risk.

And it can be double or even triple  the risk that other people will have. And so knowing that level is very, very important. 

now my understanding is that currently we can't treat lipoprotein a  what do you recommend as far as people being screened for this and what do you recommend for the current way to look at treatment 

Well, I personally believe everybody should have it done at least once in their lifetime. It doesn't change. Once you get it, it is what it is. So in their maybe early twenties, most people should have a level obtained, particularly if they have a family history of coronary heart disease and. If they have a high level, then what I tell people is, okay, we can't lower your lipoprotein A level, but we can take all the other risk factors off the table.

Get your blood pressure under good control. Make sure that your, uh, body weight is where it should be, that you exercise, that your LDL cholesterol is very low, and we can, at the very least, we can delay At the onset of atherosclerotic cardiovascular disease  by taking care of the other risk factors.

and there's nothing that they can do individually rather than just risk factor reduction As far as lowering LPA level, my understanding is that diet doesn't change it, that exercise, unfortunately, doesn't change it.

Diet doesn't change it, exercise doesn't change it. Statins don't lower it. It just, there isn't another therapy yet. But we're working on, 

And so, right now, there are 3 different trials that are in or around phase 3  , so , when do you think that , we're going to get initial data on whether treating LPA directly is going to make a difference?

well, the first of these trials,  which is a drug called Pelacarsan, as in, phase three will probably end, uh, may end in 2025. And of course. There is a delay, even if the drugs actually work, then you have to file with the FDA and the FDA has to has to chew on the data before they actually approve.

I think they would do an accelerated evaluation because of the public health interest in in doing this. But if it works. , sometime in the next several years, we're going to potentially have therapies on the market.

And the epidemiology of this shows that for very, very high levels of LPA, we're looking at almost 10 percent of the population and for high enough levels to be clinically significant, 20 percent of the population. 

We have calculated, , actually Sam Sammiches did this calculation, a very, one of the pioneers in this field, that there are 1. 4 billion people on the planet that have elevated levels, and there are 64 million people in the United States.  Uh, so this is a very. prevalent risk factor and it's a very potent risk factor. 

Currently, when you're looking at a patient who has an elevated lipoprotein A, how are you changing what their baseline therapy is? Do you have different goals for them? 

Yeah.  Lower goals for their LDL cholesterol, treat it more intensively using typically statins, , plus sometimes ezetimibe and even adding the injectable agents, the PCSK nine inhibitors that are available now, three of them that are on the market. So, yeah. Yeah, we have more aggressive goals.

I actually have lower blood pressure goals. , everything  we treat more aggressively. I, I tell people, boy, get out there and exercise, you know, maybe build some coronary collaterals, do everything you can , to avoid , having the consequences of this disorder.

So, we're going to do , something  that I thought would be a little bit fun. We're going to do a little lightning round here,  to talk about a couple of patient populations and these patient populations are all going to be essentially the same with just a couple of small changes to see how you would.

Um, all of them are 60 year old women and all of them are on high dose statin or the maximum tolerated set.  So the 1st patient is a relatively easy 1. so patient comes in with a myocardial infarction. Um, has a high dose statin LDL of a hundred and lipoprotein little a of , a hundred milligrams per deciliter, , which is certainly three times the upper limit of a normal. How would you approach that patient? 

I would probably wait. add a PCSK9 inhibitor and get their LDL down. An LDL of 100 in that patient's not good. It's not even good enough, you know, by most current guidelines, let alone with somebody with a high lipoprotein A.

the current guidelines would say that you want to get the LDL down to less than 55 after an acute MI. 

, it's complicated because unfortunately our guidelines have abandoned targets, but the European guidelines, which are more sensible would say that a very high risk patient should get below 

And are you trying  , for those patients trying to get them even lower down to 40 or, um, as many of our lipid colleagues are talking about trying to get it to 35. 

 There are two trials that took people from about 90 milligrams per deciliter down to in the mid thirties that showed benefits.  Nobody is a bigger believer that lower is better than I am. , and you know, patients ask me how low an LDL is too low. And I tell them it goes below zero.

That that's when I worry about 

All right, so the next patient is also a 60 year old female, , also on statin LDL 100 with a coronary calcium score of 100, uh, and his LPA is. 100 milligrams per deciliter.

primary prevention or secondary prevent

Primary prevention has not had a stent or bypass surgery or an MI.

100 milligrams per deciliter.  60 year woman. I haven't, I could calculate the percentile, but I guess , that 100, , Agaton score is probably up in the 90th percentile, you know, I get that patient lower. ,  How do you get there is obviously controversial. It's hard to get primary prevention patients,  to get the.

pharmacy benefit managers to let you use a PCSK9 inhibitor. So I'd probably at the very least start ezetimibe and not all high intensity statins are the same. The most potent is rosuvastatin  in the 40 milligram dose. And sometimes when you switch people from 80 milligrams of atorvastatin to 40 of rosuvastatin, you get some additional LDL lowering.

And then adding azetamibe, you can get 20%. Often. And so I think in primary prevention, I'd probably try to do it without going to an injectable agent unless I absolutely have to.

And would you start them on aspirin? 

Yes, I would start them on aspirin.

All right, so the last patient, which is a not uncommon one that we're seeing, uh, in our office now  is a 60 year old woman No prior em eye , this is so primary prevention, uh, LDL is now 100 on statins, but  has a very strong family history of early onset coronary artery disease.

So a first degree family member with an M. I. Under the age of 55, 100

said the lipoprotein A level was

milligrams per deciliter.

100 mg. Yeah. Yeah.  

This would also be the equivalent, by the way, of about 225.  to 245 nanomoles per liter.

I mean, again, this patient has a risk enhancing factor, which is,  family history. And so more intensive therapy is warranted again, using the highest potency statin available. Um, and obviously combined with diet. In some cases, when you see people like this, you find out that they're on a, a fast food diet and you can get them on a Mediterranean diet and get some additional lowering.

And then you can add ezetimibe I mean, get another perhaps 20 percent and you try to get them down to an LDL. That's that's lower. Maybe below 70 would be good. Um, it's hard to, okay. make the case for an injectable agent in these patients, but I worry about 

Clearly,  we're all trying to figure out these things. And I, and I do thank you for, , going beyond the guidelines , and giving opinions for these approaches because  unfortunately, a lot of the questions that we have in the clinic  they're not  things that we have clear clinical trial data for.

Let me make a little bit of a provacative statement. Guidelines are just guidelines. They're not mandates.  They're just suggestions for what you ought to do. But you know, everybody's got to make their own mind up about what's best for their patients. And it may be going beyond the guide.

I completely agree. I think that our guidelines, unfortunately, and I'm not going to,  criticize anyone, but our guidelines, I think a little bit behind. I think that the European guidelines are certainly more sensible.  When you start looking at these studies, you get data in front of you, you have to say, you know, I have to address this one way or another.

Completely agree.

Well, Dr. Nissen, thank you so much for taking all your time today., , uh, thank you. And, , I really appreciate all the work you've done over the years.

This has been wonderful. 

Thank you so much for having me.