Updated ESC/EAS guidelines recognize Lp(a) as a key CV risk modifier

*This transcript was generated using an AI-based transcription tool and may contain errors. It reflects the spoken content of a live webinar and has been lightly edited for clarity.

Speaker: Prof. Dr. Florian Kronenberg - Medical University of Innsbruck, Austria

Question: ​​Could you share some insights with us about the impact/importance of cardiovascular diseases in our current times? How can cardiovascular disease risk be assessed and managed?

Speaker: We know very well that cardiovascular disease is the main cause of death in our society and in most countries around the world. People are more aware of cancer and are often afraid of it, but they do not think as much about cardiovascular disease. Here, we really need a change of mindset. Knowing that this is the number one killer, we have to develop measures to lower event rates.

Usually, we focus on the main risk factors for cardiovascular disease: smoking, unhealthy lifestyle, poor diet, and low physical exercise. Then, on the other hand, we have cholesterol, especially LDL cholesterol. People think they can manage cholesterol through diet alone, this doesn’t work very well. Only roughly about 10% of cholesterol levels can be explained by diet. If cholesterol is high, we really need to use the according medications to lower it.

On the other hand, we have blood pressure, many people have elevated blood pressure and ignore it. Of course, we have diabetes, especially pre-diabetes. We have to take much more care of pre-diabetes, because we don’t want the person to progress directly to diabetes stage.

There are many points we should address. Many of those are not recognized, many are often called the “silent killers.” You will not feel that you have elevated blood pressure. You don’t feel that you have elevated LDL cholesterol. And in many cases you don’t recognize that you are going in the direction of diabetes. Those are things for which we have to develop much more awareness out in the public. That people take health examinations, that they take this seriously. Because our society will no longer be able to afford that we treat the final end of this development, in terms of development of cardiovascular disease, we have to prevent it. I think prevention is the really important point, especially when we look now also at the European level, where we say we should go away from cardiovascular disease, and we should go more in the direction of cardiovascular health. And there, I think we have lots of things to do.

Question: ​​Could you please give us an introduction to Lipoprotein(a)? What is it and why is it important?

Speaker: Lipoprotein(a), or Lp(a) is a lipoprotein, which is not very known by people. We know it for more than 60 years, we know already from the first studies in the 1970s that it is associated with cardiovascular disease. It is somehow related to LDL cholesterol, because it is an LDL particle, but there is an additional protein attached, called apolipoprotein(a). This apolipoprotein(a) is a structure with certain kringles and the number of these kringles is genetically determined. By that it is also genetically determined how high the concentration of Lp(a) is. 

That means that here we have a genetic factor, it is no longer a simple situation of a single person, because of this high genetic determination. When we have a person with high Lp(a) concentration and they have an increased risk for cardiovascular disease, then we should also look at the family, because of this genetic determination. We can expect that we might find other family members who also have elevated Lp(a), so that means we should invite the other members, like the parents, like the siblings, maybe also the children to get Lp(a) tested.

Question: Why should one measure Lp(a), when and how often?

Speaker: Because of this genetic determination, we can expect that Lp(a) remains pretty stable during lifetime. Therefore, a single measurement once in a lifetime should be appropriate for most people. There are some exceptions: for example, in kidney disease, Lp(a) concentrations can go up even further, or in liver disease, since it is produced in the liver, if you have a severe liver damage, it goes down. But in most cases it should remain relatively stable. For women, in and after menopause, Lp(a) goes up roughly 15–20%, but this will not influence the risk in most women, because most women have low concentration of Lp(a). This is also the case for men, because roughly 70% of the population has a concentration of 30mg/dL. Let’s say that for a woman after menopause, it goes up by 15-20%, it doesn’t really change the risk. When we look at this more carefully, especially for those people who are in the middle range, let’s say 30- 50 mg/dL, or when we use the other unit, this is also an important issue, the unit in which Lp(a) is measured, the other unit is nmol/L, so 75–125 nmol/L is the equivalent to 30 - 50mg/dL. So for people in this group, several of them will change to a higher group above 50mg/dL or 125nmol/L in menopause. I already touched upon a point, which we should keep in mind that there are 2 different units and most of the time, I am approached by patients or even by physicians, they call and say: “I have a person here with Lp(a) of 100.” And I always have to ask “What unit of 100?” At first they don’t know what I mean, then they have to look up what unit it is, because there is a difference if it is 100nmol/L or 100mg/dL. So when you give the concentration, don’t only give the number, always give the unit, otherwise it causes a lot of confusion. Especially here in Switzerland, in Switzerland people also report in g/L, if I remember correctly. It can be quite confusing if you don’t name the unit.

Question: What can be done today if an individual has elevated Lp(a) levels?

Speaker: This is a really important question, because many times people ask: why should I measure Lp(a) if we don’t have a drug to lower it? The answer is very clear. In the consensus paper from the European Atherosclerosis Society in 2022, we had a major focus on what we can do if someone has elevated Lp(a). And this is very clear when someone has elevated Lp(a) and has risk factors, like high LDL, high blood pressure, diabetes, unhealthy lifestyle, and so on. Then their risk is increased tremendously. I will give you an example. If a person has a lot of risk factors, as I mentioned before, and their overall lifetime risk is of 25%, but if that person has an Lp(a) concentration of 350nmol/L, or 150mg/dL, then the risk is increased from 25% to 68% of lifetime risk. This is a tremendous increase. This gives us already the answer to what we can do in such a situation. As I said, this person has a lot of risk factors, we have a target here: we should lower LDL cholesterol, we should lower the blood pressure, we should get them in a good metabolic stage, lifestyle changes, stop smoking, of course. So we can bring the overall risk down. We will not change the Lp(a) concentration, but we will bring down the overall risk. This is the main message which is valid now and will be valid also after we might have Lp(a) lowering drugs. This will always be the case, matching the other risk factors. This is more of a global risk assessment and acting on the other risk factors.

Question: Will there be Lp(a) lowering therapies available in the future?

Speaker: When it comes to Lp(a) lowering effect of drugs, it is unbelievable what they can do. These are antisense oligonucleotides therapies or siRNA-therapies that can lower Lp(a) by up to 99%. If someone working in the field had told me 25 years ago that there will be drugs capable of lowering Lp(a) by 99%, I would have said it was impossible. Now we see that it is really possible. These are injectables, but there is also movement to get oral drugs, which can also lower Lp(a) by 85%, so these are really wonderful tools and they show that we can lower Lp(a) by this dramatic amount, but we have to keep in mind that these drugs are in phase III trials, and we have to see what the outcome of these trials will be. Because it is great if you can lower Lp(a), but if you don’t also lower the cardiovascular events rate, then it is only a lab “cosmetic” situation. We are eagerly waiting for the end of these trials and this will be the first proof that lowering Lp(a) is helpful. We hope that this is the case, but we have to wait until we have these outcome studies available. We expect that within one year, so the beginning of 2026, hopefully the first outcome trial will be available, so we are eagerly awaiting that.

*This transcript was generated using an AI-based transcription tool and may contain errors. It reflects the spoken content of a live webinar and has been lightly edited for clarity.

Question: How is the current testing and reimbursement landscape looking from your experience (Austria, EU or globally)?

Speaker: This is very heterogeneous. We see when we look across the various countries, it is completely different. For example, in Austria we have the situation that everyone can get an Lp(a) test, and it is reimbursed, there is no doubt about this. We are discussing at the moment that it should become part of the new health examination, which everyone from age 18 can have on a yearly basis. It is proposed that it should include LDL cholesterol, HbA1c, as well as Lp(a) - Lp(a) at least once, it is not necessary to measure it on a yearly basis. This is the situation in Austria.

When we go for example to Germany, the situation is very different: in some areas it  is reimbursed, in others it is not the case. When we go across Europe, the picture is really heterogenous. When we go outside of Europe, it is even more heterogeneous. For example in Australia, it is almost impossible to get an Lp(a) measurement; it is not reimbursed and is very expensive. When we go in, for example, Latin American countries, it is also almost impossible to get reimbursed testing. When we go to the United States, now it is already in the National Lipid Association recommendation that it should be measured in everybody, but reimbursement is not very clear. So we have a very very heterogeneous picture.

Therefore we got together in Brussels and brought together key opinion leaders from all over the world, who are working in the field of Lp(a) : these are scientists, clinicians, but then the beauty of this summit was that we brought also people with lived experience, who are exposed to high Lp(a) concentrations in very different stages. One had experience with three heart attacks and no body had measured Lp(a) and it turned out that it was very high likelihood that Lp(a) was the culprit for this event. Others we had who had an early test as a child - we had one example - and the family, as I say, the family is very important here, somehow adjusted for that. In the sense that everyone in the family tried to have a healthy lifestyle, fight the risk factors they might have. These are different experiences people are exposed to and it was important to have the key opinion leaders, we have the people with lived experience. On the second day we brought in people from the EU parliament Parliament those interested and responsible for health issues in the European Union. But we also had people from the European and International Atherosclerosis Societies, the WHO(World Health Organization) to explain to them what the situation is, and what should be improved. With the goal that the Lp(a) measurement becomes the norm, not the exception. And the next steps to use this knowledge to prevent cardiovascular disease by doing all the things I mentioned already before, fighting the other risk factors. 

Question: The first ever Lp(a) testing cost-effectiveness study has been presented at the Lp(a) global summit. Could you please describe this ambitious project? What were the outcomes of this analysis?

Speaker: We started this international task force, the International Lp(a) Task Force. One of the goals was to make a cost-effectiveness analysis. One of the members of the task force, Professor Safina Ademi, is very experienced in cost effectiveness analysis, she did this work for familial hypercholesterolemia, for example, and we asked if she could do such a cost-effectiveness analysis for us, with an open mind about the outcome. And we were really surprised by the outcomes. 

It was shown in this analysis when we see all the costs coming from testing, coming from after we test and make recommendations that people should come into a higher risk category and  therefore take LDL-lowering drugs to bring down those risk factors, also blood pressure-lowering drugs. Considering all these costs, which are coming from that, but also considering how many heart attacks and how many strokes can be avoided - this saves costs, and on the other hand, it saves also costs when we think about the fact that if this is not done, then the person will die early, and therefore, this person is no longer in the system in a way in which he/she is contributing to the income of the country. Or if someone develops a heart attack, treatment of the heart attack creates more costs, also the rehabilitation costs, or if they are dropping out earlier from the working cycle and therefore, no longer contributing with income and also with social security payment. On the other hand, getting more social security payment, because of early retirement. They are dropping out many days per year, because of their disease, everything is considered here, and we can clearly see that if the rules are followed that it is cost saving. In high-income countries, there is no doubt about it. This can not only save lives, and we are not only saving people from heart attacks and strokes and so on, but it is also cost saving. And this is only coming from testing and the action that has to be done after testing. This was also surprising to us that it was so impressive.