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Welcome to the Quick Consult podcast, brought to you by Metall. Before starting this podcast, please review the faculty information, disclosure statements, and learning objectives using the link in the episode description. To claim your CME credit, complete the evaluation using the link in the episode description. This podcast is a continuing education activity managed and accredited by Affinity CE in collaboration with META. This activity is supported by an independent medical education grant from MSD. Welcome to Lipid Talk, a podcast series focused on closing the gaps in LDLC management for ASCVD risk reduction. I'm your host, Doctor Phil McElnay, and in this series, we'll dive into the latest evidence and practical strategies to better identify and manage high-risk patients. Today we're kicking off the long game, understanding cumulative LDLC exposure. Explore the concept of lifelong LDLC burden and its direct link to atherosclerotic cardiovascular disease. I'm pleased to be joined by our expert today, Professor Christopher Cannon, a professor of medicine at Harvard Medical School and a senior physician at Brigham and Women's Hospital in Boston. Doctor Cannon, thank you so much for joining us. Super. Well, thanks. It's a delight. Joy. ASCVD remains the leading cause of death worldwide. For many clinicians, the focus is on a patient's most recent LDLC lab result. Can you explain why it's crucial to think beyond that single number and start to think about LDLC as a lifelong cumulative exposure? Well, this is a new concept that, you know, we don't typically Typically do in the office with the patient, but what has brought this to the fore are analyses looking at people who have had long standing high LDL cholesterols, and they have higher risk than those that have lower levels over a long period of time. Various studies, some in the cohorts Framingham Risk and Eric and things. That find this cumulative exposure is a key factor in how much atheroma builds up and then longer term outcomes. Now it makes total sense, and, and I often explain to patients that it's the amount of cholesterol that your arteries have been soaking in for how long, and the longer it is, the worse, you know, the poor arteries will be, and I guess that's It's the simpleton version, but, but I think a good concept. This started really with the patients with familial hypercholesterolemia who have a single gene like an LDL receptor defect, you know, there you're born with it, so the high LDL is since births, by definition, they have a much higher exposure and those patients develop atherosclerosis at a much earlier. Age than than the rest of us. And so that's where the concept really started, but it's true for everybody, so a useful thing to consider. If the process starts early, does the timing of intervention really matter? Can you, for instance, share any data around the benefit of lowering LDLC earlier rather than later, particularly in younger, seemingly healthy adults? Yeah, and I think here the, the patients with familial hypercholesterolemia really come to mind that these are the patients that we actually start in their teens and that their LDL will often be 200 mg per deciliter, and that's twice what it should be. And so I often explain to them that, you know, we can override this genetic defect, give you medicine, get the LDL down to a normal range, and then that reduces the risk to just Being normal, and so that is where I think this started, but again, it applies to everybody. If we look at people who are non-compliant and they sort of ignore and oh the doctor wants me to do this or that, you know, they don't have a genetic, um, single gene defect that they are the people who run into trouble, so trying to get things started as early as possible is very reasonable. In clinical practice, most clinicians rely on a 10 year risk score for primary prevention in adults aged 40 to 75, given that focus on, Cumulative risk. How should a clinician apply the concept of LDL years in real world scenarios, and when might this concept push us towards earlier, more aggressive action than that 10 year risk score suggests? Um, you know, it's a wonderful question. The risk scores are, unfortunately, 75% are just your age, and so, it's just an age calculator. And so, Younger patients in their 40s and 50s, especially women, the risk comes out at 1 or 2% over the next 10 years. You know, looking at atherosclerosis in a longer term perspective, we're not doing the patients any service. So the higher the LDL, the more we worry about, you know, we've really got to get better control. And so those are patients where you start to look back. And I of course, look back, you know, at the prior LDLs and everyone. I haven't yet sort of calculated in my mind, you know, or on paper an LDL years, but more broadly a very high amount of cumulative versus medium versus low would be, I think, where I have it in my mind currently, but that might be sort of a risk. Enhancing factor that we incorporate if someone is younger, their risk score is kind of low, but they have a family history, they're a bit overweight, they're not exercising, and then you look back and their LDL has been, you know, 150, 160 for a long time, that calculates in to say, you know, this patient has had a big exposure, and I often You know, turn to imaging for atherosclerosis to really sort out the impact of the LDL, but getting a sense of has it been really high for a long time will be another important factor. The data suggests that for a patient who's accumulated a high LDLC burden, a significant reduction in LDLC is necessary to slow or even regress the Through sclerotic process. Can you elaborate on the relationship between the magnitude of LDLC lowering and the resulting reduction in cardiovascular event risk? Well, this has certainly been something seen in, in the standard trials, not necessarily in the setting of cumulative LDL, but the, the general notion that the amount of benefit relates to the amount of absolute reduction in LDL. And so if patients, you know, have a 50 versus 100 point reduction in their LDL, they'll have double the amount of clinical benefit with the greater amount of LDL reduction. So focusing on achieving a large LDL reduction has been key, and we've translated that into achieving goals of getting it down to low levels, but you know, that is the key factor and And it fits this concept of cumulative exposure, that it's the amount that's there, that's soaking into arteries, so if you can get it down a lot, then you have much less that's soaking into arteries, um, and then better outcomes, as has been seen in all the different trials. Communicating the invisible long-term nature of this risk to a patient who feels fine, can be difficult. Um, what is an effective way to communicate the Clinical significance of a patient's long-term cumulative LDLC exposure. Excellent point that we have to share this concept with our patient to make them feel what we feel. I often draw out a graph on the back of their EKG in the office and will plot out sort of the typical LDL of, of patients. It will be, you know, maybe 80 to 100, and then it creeps up in middle age and then can often get into one. 60, 170, as we're less active and eating not as well, etc. So for the patients with familial hypercholesterolemia, often there'll be a point or two at a young age, but one can actually draw and then you draw out that curve for them and say versus the typical person, here's you, that's like 2 or 2.5 times more cholesterol soaking into the arteries and simply share that with them. That they can see I'm twice as bad as, you know, the other folks, and that graph, you know, can sometimes be helpful and really sharing the data for that patient may resonate more. So that's how I try to share with patients this concept. To wrap up this episode, what is the one main takeaway you want our listeners, primary care, cardiology, allied healthcare professionals to remember. About the long term impact of LDLC exposure. Well, the basic one that we often have to overcome is that LDL, it's real, you know, there's so much misinformation that it doesn't matter. The LDL, it's all about, you know, the glucose tolerance and this and that, and of course all those other things are equally important, but the LDL impact is