Dr. Douglas Triffon discusses HDL-C and LDL-C in relation to cardiovascular disease risk.
Good morning everybody thank you so much for participating and joining us this morning um in this cardiovascular symposium we hope it's a very worthwhile endeavor and um really excited to be here and put this on. We've got an outstanding agenda and um Dr Sahar and I are my coat, my co director dr Suha and I really excited to see this come to fruition. Initially head in mind a kind of a round table discussion. We wanted to really design a format where we can really learn from each other um clinicians and people with a lot of experience who are managing. You know, a lot of number of, a large number of patients. And we really wanted to create a forum in SAn Diego where we can really create some environment where we can all learn from each other. And this kind of blossomed into this cmI event where it brings us up to today. But ideally we wanted to have a setup where we can really review and discuss management of patients and really improve our ability to counsel patients, understand how to talk to patients about diet, exercise medical therapies. We want a better be better adept at managing risk factors, understand the imaging, cardiovascular imaging and coronary imaging, coronary uh otherwise genetic information talk about women's health and really kind of get in the nitty gritty about novel medications that are coming in the pipeline as well as staff and non statin therapy is for display academia. So I think that's kind of what we put together today. We have an outstanding set of speakers. Really excited that you've joined us and we're looking forward to learning today. Um I really appreciate all the speakers that are participating. Uh really appreciate the organizers of this conference. Thank you so much and we also appreciate the industry help put this together, complete the online symposiums with the industry and with that I want to introduce my co director dr chris You are? Good morning everyone. Thank you again for being here today. Um My name's Chris Sahar, I'm the director of the script Center for Integrative Medicine. Uh I do general Cardiology, I do Integrative Medicine approaches to cardiology with a strong focus on prevention uh dr cork and I share uh equal love for preventative cardiology. This was really his brainchild. He came to me and invited me to participate with him and I'm really excited about what we put together today, as far as a really good group of amazing group of speakers, so I think we're gonna learn a lot today, so looking forward to it. Um So we're gonna jump right in first. I'm gonna start with some housekeeping. I have some course announcements. Uh I want to start with a big thank you to scripts conference services. They really made this happen for us. We had this idea right at the onset of when the pandemic uh hit and uh we didn't know if we could get this done and here we are doing it. So it's really exciting within thank you to Carlin and her amazing team and scripts. So our agenda, of course materials can be found on the scripts, health, semi conference app and the livestream event page. I do encourage you to download the app which is free for all participants. Um today's program is being recorded so and and will be available for viewing after the event. All participants will be muted during the event. Uh for best streaming results, I suggest closing down other web pages and apps that will slow down the connection as well as like any VPN or office connections. If you're trying to kind of double task and get extra work done that will just slow down your internet speeds. We love the questions. Big part of this is really trying to uh listen to our speakers but also you know if you have questions that come up we want to ask the speakers while we get a chance to win a Q and A. There is a section called ask a question, it's a button on your live feed so you can hit that and that will send the questions. We're saving the questions for our Q. And a session but you can send the questions at any point and we will collect those if your video freezes, refresh the browser and hit play to resume the video. We have an exhibit hall scavenger hunt. Please don't forget to visit the virtual exhibits during the break time. We've been really lucky to have some amazing support from industry. They have a lot to offer and I encourage you to visit download the scavenger Hunt checklist post at the bottom of the main event page. Uh and uh each and look for the hidden images for the various booths. Once you find all the images, email your completed list, if you collect this you put them in an email and email into scripts for a chance to win prizes. Um This is also an opportunity to network network with colleagues. We have a network with colleagues chat board so let us know your name and where you're from your role and connect with up just so you can get a chance to connect with other attendees. Um We also do have a big thank you at going out for the for the supporting. Uh cos again we would not be able to do this without your support. As far as c any certificates. To receive your certificate you must complete the online course evaluation and be sure to claim your credits instructions for taking the course evaluation emailed to you early next week like monday or Tuesday upon completion of the survey you will be redirected to your CMI certificate which you'll need to print and keep for your records. Uh The experience symposium right after the conference is over we have a special unique uh symposium with Dr Matthew booed off one of the leaders and preventative cardiology. Very excited to hear that talk. That is a separate link which is going to be on our page. So right with our conference ends you hit that link and I'll take you right to the symposium. So very much looking forward to that. Okay so that's all the course announcement. So we're right at eight o'clock. So I have the honour to start off the first introduction of our first speaker. So that is dr Douglas trife in uh now I've known Dr trip in my entire cardiology career um I um I was lucky enough to have him as one of my mentors and my cardiology fellowship and I'm still lucky to work alongside of him for all these years ever since. And in fact I still consider dr trip and my mentor when it comes to lipid management, he is the director of the scripts, advanced olympic clinic and I still go to him with multiple questions because he's just a plethora of information with lipid management. Uh Dr Griffin is recognized as a national speaker on the subject and always attracts a huge audience and that's why Dr cork and I were very excited when he agreed to share his wisdom at our conference. Dr Griffin was recently given the title of senior consultant here at scripts, which is a huge honor recognizing him for as many years of clinical excellence. He is also very well published in the field of atherosclerosis, lipid management and prevention. So it is an honor to introduce Dr Douglas Trip in who will be giving our kickoff lecture today on new concept in display academia. Dispelling 10 common health truths about lipids and risk assessment. Dr Griffin. Good morning everyone and thank you, Chris and David. So in 1950 It was estimated that medical knowledge would double, it would take 50 years for medical knowledge to double today. Medical knowledge doubles every 73 days. So, these truths that you and I were taught in medical school have really been proven wrong there. They've had an expiration date with the advancement of knowledge so quickly. So a lot of these truths that we hold about lipids we're going to go through and dispel 10 of them that they're expired. And we need to update our thinking. These are my disclosures. So the first truth that we need to spell is what we were taught in medical school about HDL. What we were taught is that it's a inverse linear relationship. The higher the HDL, The lower events every one mg producing the ratio increases. You have a 3-4% decrease in cardiovascular events and vice versa. When a shell is low and when we go back and again, this is what we were taught. Higher is better To the point where we would tell people do your HDL is 90. You'll never get heart disease, your cholesterol's high but don't worry about it. And we know that's wrong. So we go back to 1977. I dug out the original Framingham study where they made the association that high ratio was associated with lower cardiovascular risk. But when you look at the study it's like all of a sudden, oh my goodness! I didn't realize there were so few people. Then you look at the number of events in people who had high HBO. One event In the women were talking about seven events. This is what we based are teaching. The higher HDL is protective. So now let's fast forward to Canadians. In 2016 They looked at a few more people about 631,000 people. And they looked at the same relationship and they found, oops it's not an inverse linear relationship. It's a U. Shaped curve. And you look at the dark blue which is cardiovascular mortality. It's going up as HBO goes up. You look at non cardiovascular mortality, cancer, death. We'll get into that goes up as HBO goes up. Look at look at women, all these women that we say, oh your HDL is so wonderful. You don't have to worry. Where's the incremental decrease in cardiovascular events? Is a show goes up. It's not there again, it's a truth that is expired. What we learned in med school is no longer true today. Then we look at even the bigger study. This was a two million patients study looking at not eight events, as in Framingham, but 500 41,000 deaths. And again they find it's a U. Shaped curve Between HDL cholesterol and death. three. And so what we were told what we were taught is not valid but there's many replication repercussions of this. That will get into so nice paper this year by Norregaard summarize it. This would be the one I would have you read if you were to read one. And so yes, it's a U shaped curve, there can be confounding so alcoholism can raise a shell and increased mortality, but then they re adjusted for alcohol consumption and they still found this relationship to true. So it can be genetic variants. There are many genes that can lead to dysfunctional HBO. So is HBO grows high, you get cholesterol overloaded HBO and it's dysfunctional. They actually found confounding here that actually people with low HDL had a high prevalence of diabetes, metabolic syndrome, obesity, poor exercise habits, poor diet, high triglycerides and the genetic Mandelli in randomization trials in fact don't show any correlation with genetic higher or lower excellent cardiovascular risk. So they even called into question whether the association of low HDL and cardiac diseases really confounded by other concomitant variables that are carrying the risk. The other point he makes out is cancer cancer cells up regulate srb. One which is the receptor for drawing cholesterol out of H. D. O. So you have a cancer cell that leads a lot of cholesterol. You have a lot of H. D. O. That's feeding the cancer and so high it still has been associated with certain tumor types and increased incidents. So again there's a lot of complexity to HDL. It's no longer what you were taught in med school. So what supplants it. We've got a couple of markers that may be contenders and HBO particle number is plotted against HDL cholesterol. There's a big scout er so that I can have a patient with an HDL cholesterol of 80. But a low HDL particle of 28 I am in the habit of telling all these women You have an HDL of 90 but you really have the NHL of 28. You have low HDL because you have the risk of low HDL particle which is a stronger predictor. So here we have six trials that show HBO particle number in a multi varied equation knocks out HBO cholesterol. In predicting risk. HBO cholesterol predicted nothing for cardiovascular disease in these six trials. And so HBO particle is a stronger contender for looking at HBO risk. The other one of course is the flux capacity or an inflammatory capacity newspaper in circulation. That shows is actually closer goes up. The anti inflammatory capacity goes down again suggesting dysfunctional ex ceo as it goes higher. This is another nice paper in Jack looking at carotid plaque, volume progression of crowded plaque. Not I am T but crowded black according to different groupings of HDL cholesterol and HDL particle number. And again what we're used to thinking is here we've got a really high HDL. But with that low HBO part of number it's the highest risk group. That's not what we were talking. So all those high show they're gonna have low risk. Actually they have cholesterol overloaded. HDL is very dysfunctional. And they had higher risk than those people with low HDL cholesterol even with low ratio particle. So again this is how I like to approach HDL conundrum in the clinic. I look at both HBO cholesterol HDL particle as a ratio. And if I have this cholesterol overloaded situation with high HDL cholesterol and lower HDL particle. That is really the worst situation. So what are the ramifications of this? So if HBO cholesterol is not a good marker for cardiovascular risk then why do we use total cholesterol HDL ratio in every risk calculator that we use to decide if someone needs to stand. We put him in the pulled calculator or the Q. Ist three calculator and we're getting fooled. Now the Europeans are smarter than us. They figure this out and They realized in their latest skyline 2019 that it's a hazard to be putting a high HDL in these these risk calculating tools. You're gonna get erroneous numbers, you're going to underestimate risk. And so they came up with the first calculator that is no HDL in it. Their score calculator in in their paper in 2019 Is devoid of HDL. So they're onto this. Again, we're not in our guidelines were not in our calculators, they are with their guidelines, they are with their calculators. Again, we've known this for a long time. You can look at 2006 in the amorous trial Here's total cholesterol ratio racial performance in predicting events vs Appleby A. one particle ratio. Much more robust in capturing risk. So we've known this for a very long time yet. It's not been incorporated into guidelines. Were still using the less accurate total cholesterol ratio ratio. Look at the V. A. Hit via hit took a step further. They looked at particle number by L. D. O. Particle HBO particle ratio vs Appleby A. one versus total cholesterol ratio. Total cholesterol total cholesterol HDL ratio was the worst performer. Appleby A. One was better. But LDL ph D. O. P ratio was actually even better. Now we have to say this via hit was again in men with low HDL moderate progress arrives metabolic syndrome, prediabetic or diabetes. So this is only German in that population. But that's 40% of the the american population has these risk factors. And so in a large majority of people, we have better markers, better ratios in what we're using for a risk calculation. So I just put this here in graphic format here is the performance of total cholesterol. HDL ratio. Here's the performance of LDL ph D O. P ratio. And it was statistically significantly superior in this. Again patient demographic. So this is a workaround based again on via hit. So and I do this in all my patients. I calculate both ratios and I calculate the hazard ratios and I see how much I'm fooled if I'm using total cholesterol to ratio. So let's say I've got a total class Rachel ray show 3.5 it's a hazard ratio of 1.5. But my particle ratio is way up here. I'm going to drop up and say, well I'm going to put 5.5 is my total class ratio ratio. In my risk calculus. I don't underestimate risk Again, this should be validated in other databases. I would love to see this validating the mason trial in the Framingham offspring where they do have particle number ratios. But no one's ever look to do this in other data sets to see if we can generalize it more. But this is my work around in the clinic. So I don't use an out of date measure here of HBO cholesterol divided into total cholesterol. So the other truism that time has expired on is that lower? LDL is always better. That's what we're taught. Lower is better, lowest is best. Is that always true? And the answer is no, it's not. We can look at the epic Norfolk trial which is shown here and you can see non HBO cholesterol beach total class ratio ratio. So getting back to what we're discussing with the risk calculators. Then why don't we subtract HDL from total cholesterol rather than divided and use that in the risk calculators it's more powerful. But to the point is lower LDL better. Here's what they report an epic Norfolk. So here's a patient who has low LDL and is dead. But they had high non HDL closer. Which what that means is we've got the LDL remnants. The LDL remnants are as deadly as L. D. 01 paper from North Guard says that it's 2.5 times more powerful in predicting my than LDL. So basically we're throwing out HDL and we're putting in remnant cholesterol which again the genetic studies show if you have the genes for genetically higher remnants, you do have higher events unlike with HDL. So HDL is dropped and troubles had remission now thrown in. So again here's the patient appear who has high LDL and he's alive but he has loan on HBO. So again the lower LDL did not predict that the patient was still alive. So you can have um low LDL with high non issue and be dead. High LDL and low non issue would be alive. So LDL is not comprehensive. We can throw in here Cr P. L. P. Little a ceremonies proponents. There are many other risk modifiers that will go beyond LDL which is not comprehensive. And so it's not always true that lower is better. Here's another paper from him, offspring show the same thing. Here's a low LDL cholesterol. High LDL particle often can comment within diabetes, pre diabetes, low HDL, high triglycerides, metabolic syndrome, discordance here and the patient's dead. With low LDL and a patient with a higher LDL is alive. So again, lower LDL is not always better. There are other risk factors to consider the confound the relationship and you have to look more comprehensively if you really want to see what's going on with your patient. So building on this theme. So you got a patient after Q coronary syndrome. Should everyone's LDL be under 70 Do they all benefit equally? Again, we calculate risk and then we treat what we really should do is calculate risk and benefit and then treat and again, if you look to a website called you prevent dot com, the Europeans have already jumped ahead to this. They don't just have a risk calculator. Like we do. They have a risk benefit calculator. Take it one step further from the Switzerland paper. They have a harm so much like the has bled for a fib you could then have a risk benefit harm calculator before you start treatment. The Europeans again are much more attuned to this. They have at least gone to the benefit calculator. So looking at improving trial, they looked at people all after asks not lumping them together into one risk group, but to saying the risk is going to be androgynous. And they found four biomarkers. Supersensitive component anti pro BMP GdF 15, which is a heart failure marker in HS crp modulated the risk dramatically. Such that if you had 3 to 4 of these biomarkers, your benefit from adding is a hmeid to Staten was 7.3% absolute risk reduction, which the average risk reduction improve. It was 2.2 so you almost tripled the benefit. If you found these people who had greater risk beyond your typical demographics, we look at intermediate risk 4.4 double the benefit. But here's the hooker. If you had zero of these biomarkers you did not benefit at all in seven years from taking a zeta might on top of your stand. So not every patient with a C. S. Has the risk level that they benefit. We can look at the same thing with demographics that we reported from again improve it using the timmy's secondary risk calculator. And they found the same thing that if you have none of these nine demographics are only one of them. You did not benefit at all in seven years of taking a set of mind. If you had three or more of these demographics you had again triple the benefit. Memory treat of 16. So again not every patient benefits by lower is better after A. C. S. You have to risk stratify, which I'm a big proponent of looking at the secondary calculators, your europe as one to call the smart risk calculator. Of course that's the one I want to use. Um Similar idea. You've got a patient after him all you want to put them on the PCS can and you're gonna be very aggressive. Get that LDL down to 35. Does your patient necessarily benefit? We would like to say yes but not true. This is from the end fourier. And they showed if you didn't have high risk characteristics which again demographics you had no benefit in the three years of taking pcs can I? Even though your LDL Went to 35 went from 92 to 35. You present no benefit where those people who had high markers they had recent in mind more than two atomized high crp high opa prior bypass with recent and my poly bachelor these three vessel communities, they had triple the benefit. So again you need to risk stratify before you know what the exact benefit is for your patient. This could be shown for L. P. A. Uh in reference to dr Sumiko stock. You have low LDL. With high CRP. And for A. Or high O. P. A. You benefit less from even an LDL under 20. So just because you've got your LDL on the floor doesn't mean you have the risk on the floor. You have to look more comprehensively. Now we treat too late. Are guidelines are heavily based on age in assessing 10 year risk and they foster us treating too late. Um So actually these slides are out of order but I will take this. It'll shorten the talk. So these are people who have established cardiovascular disease And we normally think if you've got heart disease you have a 20% in your risk. And this new paper in Jack imaging shows that the guidelines saying that you should only do calcium scoring an intermediate risk is not true. These are people with symptomatic coronary disease in Denmark, who they don't do treadmills. They do sita's showing that a C to further stratify eyes risk dramatically. In coronary patients, they have obstructed three vessel disease, they have much higher risk versus two vessels versus one vessel in the rail. I opener was if you had no obstructive disease, But a calcium score over 400 that you have the same risk as obstructive single vessel disease. And they found that the number needed to treat in coronary patients could be further refined again with cita and calcium scoring. So if you had a three vessel disease number treat is only eight to lower event to vessel 14. 1 vessel 20 calcium score of a 427. So that or again, are guidelines on how to segregate risk is really not as accurate as looking at anatomy via sita. So here's what I was alluding to initially. That are guidelines suggest that we treat late in the course of the disease because they want us to treat people only when their 10 year risk is high. And so here's looking at in the red tenure risk. Here's looking at in the yellow bars number of years life saved, The greatest number of years life saved is treating four year olds. They know this in the european guidelines. They noticed in the british guidelines, they have this years ago where they have a british Joint Commission three dot org calculator calculates benefit and they show that you have more benefit in treating 40 year olds Who have significant risk factors, but they're not old enough to meet our criteria to be treated. So if I treat this 40 year old who has a 4.610 year risk, I gave him 10 more years to live. If I wait till the 65, I've lost half of his longevity, so we treat too late. So this is another myth in our guidelines is that we should only treat when the 10 year risk Is high, that in fact we should treat younger. And there's a new trial called eliminate corny heart disease where they're going to do this, they're going to start with 40 year old men treat them aggressively so they never get heart disease. So again, it's a new paradigm and it would challenge the way we do business with our guidelines. A 40 point drop in LBO early in life Is huge in terms of lifetime benefit here, 50-86% drop in lifetime risk. With only a 40 point drop in LDL young in life. Again treating earlier saves more lives than treating later. This is a myth calcium score of zero means zero risk your patients home free. Oh you're great you don't really have disease. So this is looking at three point mace. But if I look at five point mace with revascularization, unstable angina these numbers are double. So the three year incidents was 10% in people who have carotid disease and calcium score. So this paper shows that calcium score and karate kid three D plaque volume are not competitors. They're actually synergistic because they show you have policy vascular disease. If you have disease and to vascular beds it's additive to risk. But if you have a calcium score of zero your three year risk again we double this. If I look at adding the we've asked and A. C. S. So we have a 4.23 year risk. So you have about a 12% 10 year risk of a cardiovascular event. With a calcium score of zero. So again don't be fooled that a calcium score zero means 0 risk. If you've got high opa FH smoking diabetes, The recommendations are those people have about 11% in your risk and you treat them even with a calcium score of zero. So don't be lulled into that false sense of security. And I'm sure Dr Gonzalez will expand on this further in his talk. But again the new finding here is that crowded plaque volume adds to calcium score 50 calcium score on doing crosswords and I measure to D. Diameter which is as good as the three D. Volume and is equivalent to calcium score elevations so it doesn't stop here. Polly jean risk score also modulates risk. You could have a perfect lipid panel, great dying lifestyle. But if you have a high polly jean risk you can have the risk as if you had FH and this is shown in several trials where high apology in risk increases the risk about 72%. But if you have more snips measured you can actually get into the upper 5% where the risk is equivalent to an F. H. Three fourfold increase in events. Greater benefit from treatment not predicted by their cholesterol, not predicted by their demographics. So polly jean risk also I think should be integrated into our risk algorithms rather than just demographics. UcsD then interdigital dated both. So if you know polly jean Rhys score, it tells you when you want to start screening for plaque. So at UcsD they came with this algorithm. If you have a high polly jean risk where you want to screen a man with a calcium squared age 37. But it has a very good paulie Jr scored not to 49 with a woman. Hi Polly jean score screen at 49 versus age 61. If it's very low so Paula jean risk war can tell you who to treat. And also we went to screening at what age to screen. So what we've gone over here, The 10 items that HDL cholesterol is no longer what you were taught. HDL particle number is better. Maybe flux capacity, maybe anti inflammatory capacity of HD oh wait 73 days. It may change total cholesterol horatio. In our risk calculators is flawed, Europeans know that we don't L G O P H O P ratio is better. Non HDL closer will be better in our calculators. And again the Europeans have taken a show out of their calculators in 2019. Lower LDL is not always better if there's high cRP LP a particle number high remnants. Hi Paula jean risk war and cac or cita patients all benefit from LDL under 70 after A. C. S. No they don't. If their risks are low they don't PCSK nine inhibitors putting your clothes look to the floor, benefit everyone with that LDL of 35. No they don't. Cardiovascular risk is missed by calculators versus C. To absolutely calcium score of 00 risk and not true either. Low risk may be high risk. If polly jean risk is high and we have 32 seconds to spare. Thank you for your attention Wow Dr. Trevor. Thank you so much. That was extremely enlightening. I think if we had I'm also impressed you finished that in 30, 30 minutes. I know that if we had given you more time you can keep going. I know you have a long list and uh, I am also very excited to hear your next talk, which would be later today. So just a reminder to everybody, uh we have a Q and a. After these first three uh uh lectures, the Q and A. For this morning. The early morning lectures are is at 9 30 Doctor Trip in will be hanging out. So please send your questions, will be collecting them and uh and and review the questions at 9 30.