Guidance Documents: Learning About Lipids

This is Lab Medicine Rounds, a curated podcast for physicians, laboratory professionals and students. I'm your host, Justin Kreuter a transfusion medicine pathologist and assistant professor of Laboratory Medicine and pathology at Mayo Clinic. Today we're rounding with Dr. Jeff Meeusen, assistant professor of Laboratory Medicine and pathology and clinical Chemist in the division of Clinical Core Laboratory services for the Department of Laboratory Medicine and Pathology at Mayo Clinic.

Thanks for joining us today Dr. Meeusen. Yeah, thanks for having me. I'm really looking forward to talking. Yeah, so we've had you on the podcast a few times before and it's it's always wonderful to have your perspective in on things. One of the things that you've done recently that's really cool is that you've chaired a guidance document on lipid testing. And so maybe for our audience we can kick off why why is this guidance document on lipid testing significant?

Yeah, thanks. I am excited to talk about that a little bit. So it was solicited by the Association for Diagnostic Lab Medicine, so formerly A A C C or the Association for Clinical Chemistry. And as you know, and probably most of our colleagues lipids have benefited from a really big public education public health effort over the years. I mean, we all know that cholesterol is something we should watch out for. It's on the labels for our food, et cetera.

And there's been a lot of documents over the years, in fact I'd say there's been documents consistently issued for like 40 years on cholesterol and its management. So these have been refined from various societies. You know, the American Heart Association the Academy of Cardiologists, endocrinology, even, you know primary care and family medicine groups have all been working together to build a consensus on how to manage a patient's lipids and thereby manage their risk of cardiovascular disease.

But this would be the first document they've explicitly tried to target to diagnostic lab medicine professionals. So we're trying to do a step removed from the patient treatment and management and try to work towards harmonization standardization of the lipids testing side. Wow, that's really kind of surprising for me.

You know, it's kind of an outsider on this to, to hear that 'cause Yeah, I mean absolutely cholesterol, I think I think that's one of those, you know, know your numbers kind of a thing. Like you say these public health initiatives and it it's kind of surprising that we have not had some kind of a a guidance on how do we measure such a an important number in our lives. So Yeah, I'll jump in right there.

Yeah. So the, the reason we've been able to go so far and do so well is very early on the C D C and the N I H made very strong efforts towards creating commutable reference materials and working with all the big name vendors to make sure that the methods for measuring cholesterol it were very standardized.

And thanks to that the measurements that are performed at basically any clinical laboratory using any different reagents any different big box platform they're gonna pretty much give you the same answer. So that's the good news.

Nice, nice. Okay. So yeah, you brought up a, answered my question I even know I had, but yeah. Okay. So that makes sense for why it was kind of, I guess, baked in, if you will. So, so what are the important kind of takeaways for laboratory professionals to understand about this guidance that you've worked on? Yeah So by convention we've been reporting labs in the context of what the clinical management documents say.

And that's a little different than the way we typically do things in lab medicine where we measure a thousand people and say normal is this, you know, bell curve and if you're outside of that you're abnormal. Well the convention that has really grown up around lipids is that it's almost exclusively used in the realm of cardiovascular risk assessment. So then we have to give laboratorians reference ranges that really aren't normal, so to speak but desirable.

So if we were to measure a hundred people, I would say about half of us are actually above desirable cholesterol concentrations, especially depending on where you live in the United States and your lifestyle. But what we were trying to now establish and and unfortunately there was a little bit of a disparity from lab to lab, clinic to clinic.

Some people would still list the normal reference range and some people would say the desirable concentration which is less than a hundred mgs per deciliter L D L cholesterol, less than 200 mgs per deciliter total cholesterol. So we tried to provide a little guidance around that area. And then there's two other really big issues that have been coming up in very recent years and that is around low density lipoprotein cholesterol. So typically and this is the convention because of the A M A

panel. So This is the L D L cholesterol, right? Okay. L D L cholesterol, which is the bad cholesterol, right? So we can't just measure cholesterol and gauge your risk. You have to measure your cholesterol and your H D L cholesterol which is the good cholesterol that's known to be protective. And the L D L cholesterol, it turns out is what has a propensity to get clogged in the arteries causing cardiovascular disease.

And since the 1970s that L D L cholesterol has been calculated rather than measured. And we do that by taking your total cholesterol subtracting the H D L cholesterol and then we put in a fudge factor for all the other kinds of cholesterol by taking your triglycerides divided by five. Sounds like a lot of my math course. Okay. You got the fudge factor in there. Yes. And that's okay. And it worked well for many, many years because every lab is reporting it that way.

And we all understood there were some potential limitations the patient needed to be fasting 'cause that'll keep your triglycerides lower. And so the fudge factor has less of an effect, so to speak or is less relevant.

Other, other aspects that were important as you couldn't use this if a person had hyper hypertriglyceridemia for other reasons, but more modern techniques now have been developed and a couple of new equations, one out of Johns Hopkins University, it's referred to colloquially as the extended Martin equation, allows for triglycerides up to about 800 mgss per deciliter.

And another equation developed at N I H referred to often as the Sampson equation because of the first author the publication was on also can account for that elevation of triglycerides. And they do a fairly similar job in estimating L D L cholesterol And, and is there, so the the evolution of L D L is, we are still calculating it but there have been new math for how we do that calculation.

And so was that guidance document did that kind of provide some guidance over which equation or in what context, which equation? Absolutely. And so there's two parts there. I'm glad you mentioned. We're still calculating it most of the time we're still calculating it. However, there are now methods for measuring L D L cholesterol on the big blocks platforms.

They have varying degrees of precision and accuracy and most of the time they don't do any better than the calculation as long as your triglycerides are within a normal range. So it's often been a reflex test in most institutions now that we have new calculations. And so our guidance document is basically saying either of those two calculations that have been widely published and and worked on and reviewed and evaluated would be acceptable.

So we need to phase out the Friedewald equation, which is the the fudge factor of trig over five that's been universally I'd say implemented for many decades. And then the second aspect of that, so we're phrasing out Friedewald now we have new equations that do a decent job throughout a big majority of the hypertriglyceridemia.

In other situations, fasting, non-fasting it might obviate the need for the directly measured L D L cholesterol which is also routinely ordered because it does just as good a job in now much wider range of situations. So those are our two, one is a recommendation that you need to use a modern equation. And two is now we less of a recommendation and more of a statement that we should consider reevaluating when we use the measured L D L cholesterol.

So as you talk about that, you know my next question I usually kind of think about what kind of challenges do you anticipate

with implementing this guidance? And it sounds like with that, you know, there's there is some interaction with clinical colleagues and education to, to happen particularly with that second point that you mentioned about when are we actually ordering a measured L D L and and so can you kind of walk us through kind of what challenges or what kind of discussions you guys were having as a group with coming up with that? Absolutely. So oftentimes that measured L D L is built in as a reflex.

If your triglyceride happens to be over this threshold then we're just gonna do a measure. And we were speaking with our clinical colleagues and this actually helped us discover an underlying issue. That was another recommendation we made. Oftentimes the L D L cholesterol is simply reported and it might've been calculated or it might've been measured but it's not clearly distinguished in the medical record which method was used particularly in these reflex cases.

So one of our other statements we put in there is you have to state if it was calculated or measured, which is consistent with best practice lab medicine in general. And then somewhere you have to state which equation you use since it's no longer this universal equation. And I think we spent a lot of time building consensus there. I was fortunate to have a few clinicians as well as laboratorians on our writing committee panel.

Fasting is gonna be a new thing too because the new equations can handle trigs now. We don't have to be so prescriptive about fasting. Oh Okay. Which is a big boon to the lab workflow I think. So what about, is there any impact for the patients? I mean, you know, when I get my cholesterol checked I gotta be fasting for some time period before I I go and do this. Is now that we're measuring things does does this change that that game? Absolutely. So that's the other big takeaway.

Now that we've got new calculations that can accommodate high levels of triglyceride fasting is really less of a strong requirement. Unfortunately, you know how workflows work. If we show up at our doctor and he says, oh it's been a while since I had your cholesterol stop by the lab on your way out, well you're gonna show up at the lab or they're gonna ask when you last ate and they're gonna turn you away maybe if you haven't fasted overnight.

And so now we're gonna be able to offer so our recommendation is you should offer a lipid panel for non-fasting and then simply add as a result whether or not the patient was fasting. And either way you can calculate L D L cholesterol and really get the patient the care they need without the inconvenience of coming back later. So if I can paraphrase you, it's with, now with this calculated eating isn't gonna really change my number in any way.

Correct. Because L D L is much more of a stable analyte over time. It's just the fact that we've been calculating it and triglycerides have been confounder in old equation. Absolutely correct. I should have started with that. Cholesterol doesn't fluctuate with a a meal. It's pretty, it, you can only change that with long-term dietary trends or, or medication. So fasting doesn't affect your cholesterol it does affect your triglycerides which is part of the equation to calculate your cholesterol.

That's wonderful. You're bringing me back to medical school

the very important lessons and reminding me with with that in mind of, of kind of learning. One of the reasons I wanted to invite you and I think it's great for our community to kind of be aware of your guidance document. We'll of course, you know put this in the show notes and link below but also just for professionals in our community perhaps young professionals just getting started.

You know, I think this is an awesome opportunity to maybe peek behind the curtain and understand how these how these things get made. So I, I was wondering if you could kind of reflect on on your experience kind of chairing this guidance what advice do you have for others in our community that, you know, maybe have not yet participated with their societies in this way?

Or maybe they are starting to get engaged with their societies, but you know, kind of shy away from maybe taking on this kind of a, an assignment. Do you have any kind of thoughts or advice for the young professional? Absolutely. Yeah. So like everything else in life, it takes a great team and I'm very fortunate we have another lipid focused clinical chemist right here, Mayo who's my colleague, Leslie Donato she co-chaired this committee with me.

We brought in some great lipid experts and had a good bunch of chemists as well as physicians speaking specific. And so that, that way we got a, a wide range of perspectives and we're able to build consensus. And now speaking specifically to maybe people that are earlier in their career just like with your academic publications you're not necessarily making an expert statement from your own personal standing but everything you do has to be backed up by data.

So there was a lot more literature review than maybe I expected at first. I would liken it to like a book chapter or a, or a view article. A lot of, lot of studying up on the latest literature but then you can make these statements substantiated by evidence in the, in the public record in the peer reviewed literature. So it's been very rewarding great experience and I highly recommend getting involved.

Wow. Yeah, I I, I hear the teamwork component in there and I hear the, you know, surprise, maybe it's some of the work and effort that, that, that goes into it. But I, I think as you're pointing out that's really a hallmark of scholarly work and and kind of the, the reason that we are in the the type of work that we, that we are. Yeah. Well, this has been awesome. Thank you so much for joining us today. Absolutely. Thanks for having me. Nice talking with you.

So we've been rounding with Dr. Meeusen about the the new lipid testing guidance document. And to our listeners, thank you for joining us today. We invite you to share your thoughts and suggestions by email to [email protected]. If you've enjoyed this podcast please subscribe until our next rounds together. We encourage you to continue to connect lab medicine and the clinical practice through educational conversations.