What is Lipoprotein? Also Referred to as LP Little a or LP(a)

Podcast Transcript

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Ashish Sarraju, MD:

Hello everybody. My name is Dr. Ashish Sarraju. I'm a preventive cardiologist and associate staff and a researcher at the Cleveland Clinic in Cleveland, Ohio.

Today we're going to talk about lipoprotein A, or LP(a). Before we get into lipoprotein A, or LP(a), maybe it'll be helpful to first review a few things. What are lipoproteins? Well, lipoproteins are, in a simple manner, round particles made of fat or lipids and proteins that travel in your bloodstream to cells and organs throughout the body. Cholesterol and triglycerides are types of lipids found in lipoproteins.

Generally speaking, if you look at your cholesterol blood test that you get with your usual physician, you'll see different types of lipoproteins that are resulted in those tests. These include high density lipoprotein, or HDL, which has historically been simplified as the "good cholesterol," although it's not quite as cut and dry as that. HDL carries cholesterol back to your liver to essentially be flushed out of your bloodstream.

There's low density lipoprotein, or LDL, which has historically been termed the "bad cholesterol." But again, that's a very simplistic way of looking at this. But we do know that LDL increases your risk of coronary artery disease, heart attacks and stroke. It carries cholesterol that accumulates as plaque inside blood vessels, either making the blood vessels too narrow for blood to flow freely, or creating unstable plaque that can rupture, create a blood clot and cause heart attacks and strokes. The process of plaque formation inside the blood vessel, specifically the arteries of the body, is called atherosclerosis.

There are other types of lipoproteins that are resulted on your usual cholesterol panel, such as VLDL, or very low-density lipoprotein, which can carry triglycerides as well as cholesterol to your tissues, intermediate density lipoproteins, or IDL, and chylomicrons.

So which group is LP(a), or lipoprotein A? Well, generally speaking, LP(a), or lipoprotein A, can be thought of as analogous to LDL in terms of its effect on coronary artery disease. Lipoprotein A consists of a cholesterol or lipid molecule with a protein called Apolipoprotein A, or APO-A, that loops around the lipid segment and the Apolipoprotein A, or APO-A, has segments called kringles. This molecule is somewhat sticky, like LDL. As a result, LP(a) can contribute to the process of plaque building up in blood vessels, increasing the risk of cardiovascular problems. And we know from excellent data that high levels of LP(a) are a risk factor for atherosclerosis.

So how do we know if your LP(a) is elevated? Well, high cholesterol rarely causes symptoms early on. So, the best way to identify cholesterol issues is testing. So, your doctor may order a lipid blood test for screening, diagnosis or monitoring purposes to measure total cholesterol in your blood. These tests provide individual results for HDL, LDL, triglycerides and total cholesterol. Often these tests are ordered as fasting blood tests, which means that you may need to fast for eight to 12 hours before the blood test, and you should follow your healthcare provider's directions in preparing for this test.

Now, lipoprotein A, or LP(a), isn't typically a part of the routine lipid blood test that your doctor gets. So, your healthcare provider should specifically request it if needed. And physicians typically order this lipoprotein A test for patients who have risk factors, such as a personal history of heart problems or a family history of heart disease, especially heart events such as a heart attack or a stroke at a younger age in first degree relatives, if patients have unusually high LDL cholesterol levels, or if they have a condition called familial hypercholesterolemia, which is again an inherited condition that causes high LDL cholesterol levels.

So, what is a normal lipoprotein A level and what is an abnormal range? Well, in general, for these cholesterol values on a routine lipid panel or for lipoprotein A, the healthy ranges can vary depending on several factors including your age, including the other medical issues you may have. In general, though, for lipoprotein A, a reading above 50 milligrams per deciliter, or 75 nanomoles per liter is considered elevated. And is considered at a level that increases your risk for atherosclerosis and subsequent heart attacks and strokes and is considered a risk factor for heart disease much like high LDL or high blood pressure might be.

Now, note that I said there are two different units, so depending on which lab you get your lipoprotein A level tested, you may see the result as either milligram per deciliter, or NGDL, or nanomoles per liter. And depending on which unit is used, what is considered elevated changes slightly. It's not easy to directly convert one to another, so comparing two different lipoprotein A tests from two different labs may be tricky.

What about risk factors for lipoprotein, or LP(a)? Why would someone's LP(a) be elevated? Well, what we do know about LP(a) is that it is largely regulated by genetics, estimated to be 70 to perhaps more than 90% of the time. So many people who have elevated lipoprotein A inherit a gene change that regulates that. Other factors that have been associated with variation or differences in lipoprotein A levels include race and ethnicity. For example, certain populations, like South Asian populations or certain Black patients in studies with self-reported race and ethnicity groups have had higher lipoprotein A levels than self-reported patients of other race or ethnicity groups. There's a lot of active research going on into determining and better understanding the variation in lipoprotein A levels in a given population.

Stepping back from lipoprotein A though, in general, high-risk factors for high LDL levels include a diet that is high in calories, conditions like diabetes and kidney disease, family history of high cholesterol, excessive alcohol use and smoking can cause elevations in different types of lipoproteins. Certain medications, like steroids, can increase cholesterol levels. Carrying extra weight can increase cholesterol levels. Now, these factors can increase different cholesterol levels, not just the LDL, but some of these increase triglyceride levels. Some of these are associated with low HDL levels. So, these different factors that I just listed are things to keep in mind when trying to optimize, not just the cholesterol panel, but overall risk of heart disease. Lifestyle changes, and certain medications, such as statin medications can lower LDL levels or triglyceride levels in some cases.

Now how do we treat lipoprotein A? Well, lipoprotein A is not as responsive to the common cholesterol medications. Medications like statins, for example, which are proven to lower LDL cholesterol and reduce your risk of heart disease, have a neutral effect on lipoprotein A and sometimes even increase the lipoprotein A level slightly. But generally speaking, for patients who need them, their benefits far outweigh any risk of increasing the lipoprotein A level.

There are other medications that have been shown to be associated with lowering the lipoprotein A levels in studies, for example, PCSK9 inhibitors, which are injectables that can lower lipoprotein A levels to a modest degree maybe by about 25 percent. But really there's no medication that's specifically approved to lower lipoprotein A levels currently. The mainstay of treatment for someone who has a high LP(a) level, or lipoprotein A level, is to control all the other risk factors optimally and especially to lower your LDL cholesterol and apolipoprotein B level, which is another really excellent measure of total cholesterol burden that can cause heart disease. So that's what your doctor will concentrate on, is controlling all the other risk factors and making sure that your LDL cholesterol is as controlled as possible.

So, in general, good things to pursue are dietary and lifestyle changes, we remain physically active for at least 115 minutes every week to a moderate level. So, you can think of it as 30 minutes a day. Eating a heart healthy diet, managing your high blood pressure, managing diabetes, getting more sleep, maintaining a healthy weight, and trying to decrease your level of unhealthy fat that you're carrying in the body, finding healthy ways to manage your stress and reducing smoking and controlling or reducing alcohol consumption.

So, I hope that was helpful. We have a few specific questions from patients which we'll go through to help answer, maybe some questions that some of you listening to this podcast may have.

Question one is, what is the latest treatment for high lipoprotein A and what impacts do statins have on lipoprotein A? And we briefly addressed this, but to review this, for high lipoprotein A levels, currently there are no approved treatments to specifically lower it. Statins are excellent drugs to lower LDL cholesterol and are indicated for many patients with risk factors, high cholesterol or a history of heart disease, but they have a neutral effect on lipoprotein A and can slightly increase it. But for patients who have an indication for statins, generally the benefits of being on it outweigh any risk of increasing the lipoprotein A. But this is something your doctor can go over and individualize to your specific medical picture.

There are many therapies that are under investigation for lipoprotein A that are in clinical trials and that are anticipated to be completed over the next several years. So, research is moving fast and it's not inconceivable to think that there will be treatments on the horizon to specifically lower lipoprotein A depending on the results of the clinical trials. So, is there anything that can be done currently to lower it? Well, there are certain medications, as we briefly discussed before, that can decrease lipoprotein A, but are not specifically approved for it. PCSK9 inhibitors in patients who have a specific indication for those, if those patients have an elevated lipoprotein A, we may find that the PCSK9 inhibitor also lowers the lipoprotein A. Whether that directly leads to decreased cardiac events, that hasn't been established definitively. There are other therapies that we know decrease lipoprotein A, like niacin and estrogen therapy, but these generally aren't considered first-line to specifically treat lipoprotein A. Niacin, for example, can have several adverse effects when used. So generally speaking, it's not preferred by doctors.

The next question asks, can you discuss lipoprotein A, what abnormal levels mean and what we need to do to reduce our risk factors for complications? That's a great question, and I hope our discussion earlier was helpful in answering this particular question.

Is the medication worth taking when you have a high lipoprotein A and a zero CT calcium score? That's a great question. It's a very specific question that also asks about another data point that helps us understand a person's risk for future events. That is the CT calcium score. Now, this is a very specific question, so I would say discussing this with your physician is probably the most important answer here because something like this has to be individualized to your specific medical history. But with a zero CT calcium score and a high lipoprotein A, there may be some cases where a medication like Crestor is indicated. For example, if the LDL cholesterol is extremely elevated and there's concern for something like familial hypercholesterolemia, which is a genetic condition of high LDL levels, then a statin medication may still be indicated even if the calcium score is zero.

In other cases, if the calcium score is zero, sometimes healthcare providers may decide not to pursue statin therapy, but they may take into account the high lipoprotein A level and choose to follow your cholesterol levels closely and optimize all the other factors that can lead to heart disease. So, as you can see, it can be nuanced, and it is something that really should be discussed with your doctor.

So, to conclude, I hope this was a helpful discussion of lipoprotein A level. This is an emerging risk factor for atherosclerosis or heart disease. There is a lot of ongoing research, and we anticipate advances on this topic in the coming years. And if you have any concerns or questions about either a family history of heart disease or an elevated lipoprotein A, the Preventive Cardiology Clinic at the Cleveland Clinic specializes in these topics, including lipoprotein A levels. So please feel free to reach out if there are concerns on this topic. Thank you very much.

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