Time Stamps

  • 01:24 Intro 
  • 03:37 Fasting vs. Nonfasting Lipid Panel
  • 05:11 Current guidelines
  • 07:43 Pathophysiology Overview
  • 09:04 Pathophysiology of Apo-B vs. LDL-C with traffic analogy
  • 11:23 Apo-B 
  • 15:40 TG-to-HDL ratio
  • 17:06 Takeaways

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Show Notes



Greg: I had a patient come to see me recently for a second opinion because he had at least three acute coronary syndromes and had progressive cardiovascular disease. I think he had about 15 stents and he brought this stack of blood work with him from the last decade of his life and his LDL cholesterol on a high potency statin ranged from 42 to 49 milligrams per deciliter over all of that time. He didn’t have diabetes, he didn’t smoke yet he had progressive cardiovascular disease.

Cary: That kind of disturbs me, Greg, that really doesn’t make any sense to me cuz this patient like seems to be doing really well. I can’t even think about another way to modify this guys risk to help reduce his chance of having another event.

Greg: That speaks to one of the weaknesses in using only LDL cholesterol as the metric we are doing to evaluate cardiovascular risk. And so I think that there’s a lot of other information that we can get when we look at the rest of a lipid panel. And there’s also a lot of information we can get. If we’re willing to do a little bit more lab work in order to figure out how somebody’s doing from a cardiovascular risk perspective.

Cary: So clearly I have a little bit of room to learn about how to interpret a lipid panel. Welcome to Mind the Gap. I’m Dr. Carrie Blum.

Greg: And I’m Dr. Greg Kaz. And today we’re gonna be talking about reimagining a lipid panel to better evaluate cardiovascular disease risk.

Cary: Now that I have you as a captive audience, Greg, I would like to talk about some things today. So first, let’s cover fasting versus non fasting lipid panel. Do you really need to send your patient back if they haven’t fasted? Second, I would briefly like to talk about what our current guidelines say regarding treating lipids.

Greg: And then third, I’m going to make you talk a little bit about the pathophysiology, which will set us up really well for our fourth topic, which are the two lab tests that I look at most to think about cardiovascular risk. The first is APO lipoprotein B and the second is the triglyceride to HDL cholesterol ratio.

Cary: Then at the end, we’re gonna think a little bit about what our ideal lipid panel would actually look like. Maybe we can design one that would actually catch that patient. And identify him as somebody at as higher risk So first of all question that comes up all the time, both my colleagues, my residents and my patients is regarding fasting and the need to fast before a lipid sample.

Greg: So, the way I think about this is that the impact of eating versus not eating is pretty minimal. It doesn’t really affect the HDL. The LDL is gonna be a really slight change. The triglycerides are gonna be where you see the biggest impact on fasting versus not fasting, but, you know, overall, I think that it’s much more important to get this test done on a patient than it is to make sure that they come back when they haven’t eaten for eight hours and you can have a little bit more of a clean sample. And so I just wanna know, have they eaten, or have they not eaten when I’m interpreting the test, but I don’t force them to come back if its more convenient for them to just get the test on the way out of their visit

Cary: Makes sense. And, you know, luckily I actually have some data there. Greg, the numbers when you fast, prior to a lipid panel, barely change for HDL. If you’re eating, they’ll go up a little bit for LDL cholesterol and non HDL cholesterol, but the mean is only around eight milligrams per deciliter. So if a patients not fasting and you want to do an adjustment, I’d say subtract around 10 or so from the LDL, the triglycerides are the one that, like you mentioned that go up the most after eating. The average is about 25 milligrams per deciliter. So if you know, your patient is not fasting, subtract around 25 or so from the result and that should get you close to where you need to be.

Greg: Okay that’s an easy adjustment to make

Cary: So let’s look at what our current guidelines say. There’s really two sets of guidelines. There’s the ACC, AHA, and the USPSTF. They share a lot of similarities. Both of them recommend calculating a 10 year risk of ASCVD, and then making a prescription for a statin depending on what the numbers come out to be a good cutoff to remember is 7.5%.

Greg: And so all of these risk calculators for the most part, risk across 10 years, but for a 40 year old patient who has risk, do I just care about the next 10 years? I would say no, I think I care about a much longer time horizon. And so the idea of doing just a very short course of of evaluating risk with these 10 year calculators is probably not good enough for most of our patients.

Cary: That’s a great point, Greg. I think the guidelines just don’t incorporate that recommendation because it would take. An enormously long randomized controlled trial to prove a benefit for statins and patients who are young and relatively low risk for 10 year ASCVD.

Greg: This kind of gets to the idea of how much is it acceptable to extrapolate based on the data that we have and how much do you need a randomized control trial to really guide your clinical decision making. And so if you are waiting on the idea of 30 year clinical trial to figure out about treating people who are in their forties and who are vulnerable, you’re never gonna get that. But I think if you take the sum total of that literature, it really suggests that this is about area under the curve. This is about exposure over time and the longer somebody is exposed to high levels of atherogenic lipoproteins, the higher their risk is. And so I look at the sum total of all that data. I look at all of those Kaplan Meier curves, and it really says to me that lower is better and lower across a long time horizon is definitely better as well. We know from autopsy evidence of young people who died at war that fatty streaks are present in the aorta in twenties and thirties, and maybe even younger and so the idea that you wanna wait until coronary artery disease or atherosclerotic cardiovascular disease becomes severe and late in life before you take it seriously to me, just doesn’t compute and doesn’t really make sense.

Cary: Well, as a 34 year old without the healthiest lipid panel hearing that from my trusted friend and the cardiologist definitely makes me feel better about the fact that I just started statins

Greg: I think a lot of people take that decision initially about prescribe or not prescribe and then they move from a risk assessment to an LDL centric mindset where they’re just focused on the LDL cholesterol as the only metric to decide whether or not their treatment is successful or needs to be increased or decreased or whatever.

Cary: And clearly, you know, I think as we’ll probably get into it a little bit more as we go forward, that’s probably inadequate. Like, for example, the patient that you had who had an LDL in the forties, would’ve been missed with that approach.

Greg: Yeah I totally agree. And that’s part of why I sent him for a bunch of other lab testing and why I examined the rest of his lipid panel in addition to just his LDL cholesterol.

Cary: And I like when I’m talking to patients, I often will bring up the pathophysiology of atherosclerosis. We know that it starts young, it starts in the twenties, thirties. And so if the pathophysiology is there, if your arteries are being affected by this process it makes sense to slow it down if you can.

Greg: On a lipid panel, You get information about two separate pathophysiologic processes that are really, really important here. Number one is you get insight into the number of particles that are traveling around and can get into the wall of the blood vessel causing atherosclerosis. And number two, you get information about somebody’s metabolic health or their level of insulin resistance. And those two things, the atherogenic particle burden and the degree of metabolic syndrome are really, really informative. And they’re two different pathophysiologic processes that are gonna influence the development of cardiovascular

Cary: So Greg, you know, earlier in the episode you mentioned that you really like to check the ApoB level and calculate triglyceride to HDL level. I really wanna get back into that because I gotta admit, those aren’t really metrics that I’ve thought about much in the past. Can you help explain to me how each of those tests? The ApoB level and then the triglyceride to HDL ratio helps us understand about the ways that our patients biology is contributing to their risk for atherosclerosis.

Greg: So it, it all comes back to how does heart disease happen? And it starts out with cholesterol getting into the walls of blood vessels, causing inflammation and leading to plaque development. But cholesterol can’t travel through the bloodstream by itself. It needs to be carried. Proteins because cholesterol's fat soluble and blood is water. And so the major protein that anchors every single type of cholesterol carrying particle is Apolipoprotein B. And so every single thing from that alphabet soup of LDL, VLDL, IDL, LP little a that you have
heard that can cause atherosclerosis has one APO lipoprotein B molecule attached to it. And by understanding ApoB you get a ton of information about somebody’s atherogenic risk. I think of this a lot, like traffic. If I tell you that there are a thousand people traveling up first avenue that doesn’t tell you as much information about what the traffic is like, as if I tell you there’s 10 buses going up first avenue or a thousand cars. And so LDL cholesterol, which is that metric on a lipid panel that we all look at, tells you about the number of people traveling up the street, but APO B tells you about the number of cars on the road. And if at the end of the day, traffic is what drives risk. Knowing the number of cars on the road is gonna be much more informative than number of people traveling up the street.

Cary: Okay, cool. The traffic analogy I have to say is got me there. So thanks, Greg.

Greg: Everybody hates traffic, just like everybody should hate a high amount of APO B.

Cary: Yeah, you know, I’m thinking about like the suburbs say on a day when nobody’s carpooling. You have one person per car. You may have a relatively low LDL in that situation, but you’re gonna have a horrible traffic jam. So anyway, take public transportation. So Greg, if APO B is really that much better than L DLC non HDLC. Why didn’t we start with that from the beginning? Like why is that not something that we’ve been measuring from day one?

Greg: Like the same reason we do almost everything in medicine because of historical accidents and the order that things were discovered in. And so we knew cholesterol was associated with cardiovascular disease based on autopsy studies and then we sub fractionated cholesterol into different densities and that it took a long time to recognize that it was actually the particles floating through circulation that mediated risk more than just the amount of cholesterol that they were carrying. And so just like everything else, it’s the order that things were discovered.

Cary: So I think that you’ve convinced me that I need to at least keep more of an open mind to ApoB. Maybe I should be ordering it more, but if LDL does a pretty good job on a population level, then can’t we just check that? Do we really need to order yet another lab test?

Greg: If you talk to some of the people who think a ApoB is a waste of money, and it’s not honestly that much money, it’s like four to $14 to actually get that assay done. But if you talk to the people who think that a ApoB is a waste of money, what they’ll tell you is that across a population, LDL cholesterol is fine because it tracks with ApoB, but we don’t treat populations, we treat patients and the individual patient in front of you may have. A high ApoB, but a low LDL cholesterol or a normal LDL cholesterol. And so I think if you wanna take care of the person who’s sitting across the room from you and you don’t know what their ApoB is, I don’t think that you actually have a sense of what their atherogenic lipoprotein risk is gonna be for cardiovascular disease. So, you know, my bias is that if we’re going to use a biomarker, we should use the right biomarker instead of the wrong one. And ApoB is the right one and LDL isn’t got it.

Cary: Let me go to another value that is often calculated for me on the lipid panel, the non HDL cholesterol. I know that that also correlates a little bit better with atherogenesis than LDL C. Is that something that is of value? Is that something you use in your practice?

Greg: So non HDL is certainly better than LDL, but it’s also not as good as a ApoB. There are what we call discordance analyses, which are studies that look at patients who have a high percentile of ApoB and a low percentile of non HDL cholesterol, and vice versa. And what you see is that if there is any discrepancy in what the ApoB is versus what the non HDL is, ApoB always wins just like it always wins against LDL. And so I’m not saying that non HDL isn’t better than LDL because it absolutely is, but its not the best. And when somebody’s managing my lipid panel, I want them to be looking at the best marker rather than just a pretty good surrogate marker.

Cary: So I need some numbers, I think of like the median LDL in the population somewhere around maybe 120, 130. Yes. What, what about ApoB?

Greg: I have this chart which we’ll link to in the show notes I basically look at the percentile across a healthy population of ApoB and then I relate it to an LDL cholesterol percentile number. And so the kind of reference ranges that I’ll use is an LDL cholesterol of 130 is equivalent to an ApoB B of about 95. An LDL cholesterol of 100 is equal to an ApoB of about 80 an LDL cholesterol of 70 is equal to an ApoB of about 55. And you know, the threshold for which you start therapy is gonna be dependent on  who the patient is and what their risk tolerance is. But if you’re talking about the patient who has established cardiovascular disease, Anything other than an ApoB under 40 probably leaves them with residual cardiovascular risk. And so that’s kind of how I guide therapy is I aim to get it around 40. But there’s never been a study that’s shown that there’s such thing as too low. I’m sure that there is because everything in biology is a U-shaped curve, but so far lower seems to be better almost without exception.

Cary: You know, there’s that one other thing on the lipid panel, the triglycerides, which up until fairly recently, I basically ignored. But I have a feeling I’m doing that wrong, Greg, please let me know how I should be doing this.

Greg: So I think most people use the HDL on a lipid panel as a way of figuring out the non HDL cholesterol, and then they just discard move on. And I’ve had a lot of really smart physicians tell me that they just ignore the  triglycerides because they don’t really know what to do with it. I use triglycerides and HDL together to help me figure out metabolic health and insulin sensitivity. And so what I mean by that is if you look at somebody’s triglycerideride to HDL ratio, it tells you a ton about how healthy they are. An ideal triglycerides to HDL ratio is one to one. How many times have you seen the patient who has diabetes or prediabetes and abdominal fat and high blood pressure and all of the classic signs of metabolic syndrome and their triglycerides are 215 and their HDL cholesterol is 29 milligrams per deciliter.

Cary: And I think I’ve had five of those patients this morning, actually.

Greg: Yeah. It’s so over and over and over again. And that’s probably the most common lipid abnormality that I see. And when I see a triglyceride to HDL ratio that looks like that, that tells me somebody’s not very metabolically healthy and that they have poor insulin sensitivity.

Cary: All right, Greg. So here we are, first of all, thank you. I’ve learned a lot let me ask you this question. If you had to redesign the lipid panel, if you were to add something to it, maybe even get rid of something, what would you do?

Greg: You know, I think it’s pretty close to what we have now. I would get a total cholesterol, an HDL cholesterol, a triglyceride level, an apolipoprotein B and maybe I’m throwing out the LDL cholesterol from the lipid panel, which may be provocative. But again, like APO B is a better metric.

Cary: No, you didn’t, Greg, you just threw out the LDLC. Well, we’re gonna have to figure out how to teach how to teach everybody how to interpret them now. But that’s a good goal, I think, because it will help us take care of our patients a little bit better. So at the end of the day I think I’m gonna be ordering a little bit more APO lipoprotein B. and it’s not like ApoB is even all that much more expensive. You mentioned it’s a cheap test.

Greg: I mean the Europeans and the Canadians are already doing it. And so it’s just a matter of time before we Americans catch up.

Cary: So what I’m taking away today is first of all, I’m not gonna make my patients fast for a lipid panel. If I knew that they were eating, I would probably subtract about 25 from the triglycerides and about 10 from the LDL. Second, I think LDL, you know, like you said, while it works pretty well for populations is just not as good of a biomarker as we have available in apolipoprotein B. So I’ll be ordering that more. And last but not least, I don’t think I will be skipping the triglycerides and HDL anymore. I’ll take a look at those and probably calculate the triglyceride to HDL ratio in order to determine my patient’s risk for insulin resistance and diabetes. There’s probably a whole other episode worth of talking about how do we treat patients with dyslipidemia, i.e. Statins and other therapies. What do you think, Greg, should we meet up again and talk about how to get the number cars off the road?

Greg: I can’t wait to have a conversation about why that statin makes my muscles ache.

Cary: I’m gonna be driving in the HOV lane for that conversation.

Greg: All right, and that’s it for today’s episode. If you found this episode helpful, please share with your team and colleagues and give a rating on Apple Podcasts or whatever podcast app you used. It really does help people find us. Tweet us, leave us a comment on our website, Instagram or Facebook page.

Cary: Thank you to Yichi Zhang for the audio editing and Lizzie Holland for the accompanying graphic. As always, we love hearing feedback, so email us at hello@coreimpodcast.com. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.

Greg: Listening to this podcast does not constitute the formation of a doctor-patient relationship, and nothing that you heard should be construed as personalized medical advice. 



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