Hypercholesterolemia

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Hello and welcome to this BMJ best practice topic on hypercholesterolemia. Kieran Walsh is my name. I'm clinical director at BMJ. Hypercholesterolemia is a common condition. 10% of the adult population in the US have total cholesterol levels of more than 6.2 millimoles per liter. But of course, we know that hypercholesterolemia is associated with heart disease.

stroke, peripheral vascular disease, and much more. So it is a significant problem. To give us more details about this problem and what we can do about it, we have on the line Thorsten Leiker. Associate Professor of Medicine in the Division of Cardiology at the Johns Hopkins University School of Medicine. And importantly, Thurston is author of our BMJ Best Practice topic on hypercholesterolemia.

Sir Thorsten, you're welcome. Let's start off by asking, what exactly is this condition? Thank you for having me. I'm very excited to be here and talk about this very important topic. So when it comes to hypercholesterolemia, hypercholesterolemia comes in several different flavors, maybe just a distinction between two important clinical... findings one would be pure hypercholesterolemia which is referring to an elevated LDL cholesterol

And then we often also encounter in clinic a mixed-type lipidemia, which would refer to elevated LDL cholesterol as well as triglycerides. Both of these conditions are highly arthrogenic and have shown in...

several studies to lead to arthroskelogic cardiovascular disease and are closely associated with cardiovascular events. Thank you. How do you make the diagnosis? The diagnosis is mostly made by general practitioners when they order lipid panels, and we can assess the different lipid fractions on these lipid panels.

Other important factors that go into making the diagnosis is family history. Often the first encounter is a patient coming with a significant family history and asking about personal risk and then on the big panel. would be downstream to diagnose any lipid abnormalities, meaning the two that I just mentioned. Okay, great. And when you say lipid panel, what specifically would you be testing for in a lipid panel typically?

Yeah, that's a very, very good question. So traditionally, we would get just the standard lipid panel, which includes a total cholesterol, an HDL cholesterol or the good cholesterol, triglycerides, as well as an LDL cholesterol. And LDL cholesterol is actually calculated. The other three are directly measured on the panel. I would say in December of 2024 that we should be more comprehensive than this.

And in my clinic, I always also get a lipoprotein A, which is the newest kit on the block, as well as an apolipoprotein B, B100, which is the general marker on all aterogenic lipoproteins together. good understanding what the total burden of arteriogenic lipoportuents does. Okay, thank you. And any other tests, I wonder, that might be relevant in the initial phase? Yeah.

So I usually do a very comprehensive cardiovascular risk assessment, and that includes markers of glycemic controls on hemoglobin A1C. I usually get a general assessment of kidney and liver function on a comprehensive metabolic. panel. And then in special circumstances, I would also assess inflammation and I would get an HSCRP or high sensitivity CRP.

in my patients to really get a comprehensive assessment, comprehensive biomarker assessment of their cardiovascular risk alongside with physical exam and family history, of course, or other. important factors, as well as learning more about lifestyle, dietary habit of the patients as well. Fantastic. Thank you. Any pitfalls in diagnosis, I wonder? No test is perfect, of course. In general, I think lipid panels are a good test to start with.

When it comes to assessing the LDL cholesterol, though there's one potential pitfall that, as I mentioned, the LDL cholesterol on the standard of the panel is not measured, it's actually calculated. And so the lipoprotein A, a very close cousin, I would call it, of LDL cholesterol, also highly heterogenic, is...

part of the LDL calculation. So sometimes we see patients that have an elevated LDL cholesterol where indeed the majority of this LDL is LB-L-A and not LDL cholesterol. Other pitfalls are that If you are assessing for triglyceride levels on a lipid panel, it's important that the patient is fasting prior to obtaining the lipid panel. Otherwise, triglycerides can be falsely elevated on this. This does not.

matter much for the LDL cholesterol. LDL cholesterol is not generally impacted by a non-fasting state acutely. But this would be two pitfalls that I could think with. And then it is always important to see the lipid panel in the greater context of the general appearance of the patient. and other potential cardiovascular risk factors like glycemic control, for example, can heavily impact triglyceride levels or triglyceride metabolism.

body weight and physical activity levels can impact triglyceride levels tremendously when again it comes to LDL cholesterol. that is mostly impacted by genetic factors and less by lifestyle factors, since the majority of LDL cholesterol is actually produced by the liver and not coming from the diet. Okay.

Thank you. Let's move on to management. What's the mainstay of management? Yeah, I made an important point of distinguishing between different kind of... patterns seen on the general lipid panel, meaning the pure hypercholesterolemia, mostly an elevated LDL cholesterol versus the mixed picture, which is triglycerides as well as LDL cholesterol elevated.

Just separating these two for an elevated LDL cholesterol, the mainstay of therapy is statin medications when we're thinking about pharmacological therapies. elevated triglycerides and LDL cholesterol. A statin is still a good starting point if the triglycerides are less than 500 milligrams per deciliter.

If triglycerides are above 500 milligrams per deciliter, we think about more targeted triglyceride-blowing therapies, and that can include prescription strength, omega-3 fatty acids, as well as phenofibrates. And then kind of a third line would be niacin, which we rarely use these days, since there's more important therapies available. However, even before pharmacotherapy, the most important thing is again to...

assess the patient comprehensively and think about lifestyle as well as the general risk for cardiovascular events based on family history and other risk factors. So lifestyle modification would be the first. step to thinking about regular aerobic physical activity, following a mostly Mediterranean-style diet, avoiding tobacco products at all costs, limiting alcohol consumption as much as possible.

before thinking about the next step, then, pharmacotherapies. Okay, thank you. Would you start people on a high-dose statum? Yeah, it depends on what the goal is, what the... LDL cholesterol target this in patients and so I would separate this between primary and secondary prevention, meaning primary prevention people at risk that don't have established atherosclerotic cardiovascular disease versus secondary prevention.

people that have evidence of arthrosclerotic cardiovascular disease, and that can be imaging evidence and or prior cardiovascular events. In North America, currently the guidelines are still setting an LDL cholesterol level of less than 70 mg per liter for people with secondary prevention, although... Following the European guidelines and the most recent ACC consensus statement, I think there are less than 55 mg per deciliter, or even following the concept, the lowest the better.

for LDL cholesterol, particularly in the highest risk patients, meaning the ones that already had naturopelotic event, is certainly appropriate. And so in selecting the agents in secondary prevention where the LDL... targets are lower, I usually start with a high-intensity statin, a total statin, or a super statin are usually my first choices. Okay, thank you. And what target LDL?

would you aim to achieve? Or does that depend? Yeah, in my clinic, I'm targeting for secondary prevention, usually an LDL of less than 55 milligrams per deciliter. And in primary prevention, usually an LDL cholesterol of less than 100 milligrams per deciliter would be the targets that I'm looking for. Again, the target should be individualized, in my opinion, based on the general cardiovascular risk of the patient and other factors that flow in there.

often we see people that have concomitantly elevated LDL and LP-Low-A, or like 14A levels, where one might choose an even lower LDL cholesterol target to overall lower the burden of articulogenic lab proteins.

Okay, thank you. Let's go on to pitfalls in management. What are the main pitfalls in management? Yep. Very important question. I think compliance is an important question to assess, particularly when patients have less than an expected LDL cholesterol lowering on their medication. And compliance often goes with side effects of medications. So it's important to educate patients about potential side effects from lipid-lowering therapies. They're usually well tolerated.

However, there are specific side effects to each of the different agents. And so one important factor there is that side effects can impact compliance on therapies. I think when it comes to the therapies, it's always important to assess what the underlying lipid abnormalities is to choose the right agent to target the patient's personalized needs when it comes to that.

I usually use an approach of starting with a single agent and then maximizing the agent before adding additional agents. But again, that is individualized. Some people tolerate, for example. lower intensity statins, but not higher intensity statins. And so in a case like that, I would then add on a secondary agent like zedamide, for example, or more recently also, Ampaduic acid on the earlier side.

if I am not able to escalate the doors of the staff. Thanks, Torsten. I thought I had a very clever question for you, but I think you answered it, which is that... the side effects of statins can be dose-dependent? Is that correct? Yeah, no, you're absolutely correct. Again, statin side effects are rare, kind of in the ballpark of 1% of patients taking statin medication. pretty significant if they occur, but they are dose dependent.

A very good approach, in my opinion, is, for example, if there is a patient that has had side effects to high-intensity statins or is hesitant to go to the highest dose of the statin medication, it's too... to use a moderate-intensity statin in addition to adetamide, which is equally effective as a high-intensity statin in terms of LDL cholesterol lowering. Okay, let's move on to old age. See if you have an...

85-year-old patient and they've got stable angina. Would you start them on a statin? Yeah, I would hope that that patient already is on a statin. However, if the patient is not on a statin, I think even more recently, the evidence is emerging on multiple clinical trials showing the benefit of long-term statin. therapy even in older individuals in terms of cardiovascular risk reduction. So yes, absolutely, I would start this first on a stat medication.

Okay, that's interesting. I'm a geriatrician by background, but it's moved on a bit in the past few years, the evidence base. Let's talk about patient communication and risk perception. Because you're talking to patients, about potential benefits and potential risks of new treatments. How do you do that, Thurston? Yeah, I use an approach of... talking about the lifetime exposure to elevated cholesterol. And so there is a push.

by North American and European guidelines to capture people even on the earlier spectrum and risk assess patients even on the earlier spectrum and being more preventative, proactive rather than being reactive. meaning capturing the patients before they have their cardiovascular events. And so the approach that I usually take is to counsel patients about the risks, the long-term exposure risk to high cholesterol levels and what that does in terms of...

development and progression of arteriospeleotic disease. The risk-benefit discussion is important because by the end of the day, when it comes to compliance, it's important. that the patient understands the treatments, understands what the benefits of the treatments are, and most importantly, is aware of potential side effects of the treatment, so to have the best chance of compliance to the therapies.

And so I think that these discussions are important to have and not to force any communications on the patient, but establish a physician-patient relationship that is based on trust and fully informing the patient about... and the risks, benefits, and side effects of any of these therapies. Again, they're mostly well-tolerated, but side effects can occur, and it's important that the patient communicates that to the physician. Great.

Thank you. So I'm asking you tougher and tougher questions, Torsten. Torsten, what would you expect to achieve through diet? It depends, again, on the lipid fraction. When it comes to triglycerides, and we're mostly concerned about ELDL, very low density triglycerides, which are highly arthrogenic. Diet and lifestyle can have a great impact on triglyceride lowering by activating the lipox protein lipase activity.

and thereby tremendously lowering triglycerides. In terms of LDL cholesterol, there is some impact of diet and lifestyle on LDL cholesterol. There was a study called the Dietary Portfolio that showed this. a few years back. However, when it comes to LDL cholesterol, I think the effect of diet and lifestyle of a healthy diet and lifestyle is mostly of making blood vessels more resilient.

strengthening the blood vessels so that they're more resilient or resistant to supply cholesterol rather than having a direct impact on the LDL cholesterol itself. Okay, thank you. So some super short answers, please. Any tips, one or two tips on familial hypercholesterolemia?

Absolutely. Recognition is the most important factor here. So if there is a patient, even a young patient, that has a significant family history of arthrocylotic cardiovascular disease, it's very important to screen people very early because we can... prevent the consequences of familial hyperglycerolemia. I'm a big advocate for genetic testing. We are very active in our clinic in doing so, doing cascade testing in the whole family. But again, recognition is the most important deal.

channel practitioner is key here to us. Great. And I've read about a new class of drug. I'll try and get it correct. PCSK9 inhibitors. Tell us about those. Absolutely. PCSK9 inhibitors are very potent, very effective on LDL cholesterol-lowering agents that are subcutaneous injection every 14 days. for the standard monoclonal antibodies. And then the newest kit on the block are in Cliziron. And SIRNA against LpLolA is three times the first year and only twice every year after. Okay, thank you.

Two questions left, Thorsten. We're nearly there. Thanks for bearing with me. First of all, a question about questions. Anything we've missed? Any other things that people commonly ask you? than I haven't asked you. I think raising awareness about lipoprotein A is important. I would suggest that this is widely tested by channel on practitioners. There are therapies on the horizon.

ongoing clinical trials, and we like to hear blood results in the near future. And so I think in 2024, it's important to test alpulola in every patient. Thanks. Torsten, one last question, and I promise this is the last one. What is the toughest question I could ask you? What question, when do you hear it, do you think, oh gosh?

That's a really tough one. I'm not too sure how to answer that. What is that question? And what's the answer to that question as well? Yeah, that's a good question. I have to think about that a minute. I think one of the more challenging questions that I get is when patients go on the internet and learn about side effects of medications, which I think often are...

blown out of proportion, particularly when it comes to statin medications. Statin medications are in general a safe medication side effect profile. They're usually very benign. But very often I encounter patients that have rats. a great deal about these stations and have a great fear of starting these stations because of this. Okay. Thank you very much, Toristen. And thanks to you all for listening. We hope that this has been helpful.

We hope you'll be able to put what you've learned into action to better diagnose and manage affected patients. If you want to find out more, click the link in the podcast to sign in to B&J Best Practice and look at the content on this. and other relevant diseases. Thank you once again.