With heart disease deaths on the upswing since 2010, primary care providers must routinely develop individualized plans to protect their patients from atherosclerosis. This talk from UCSF heart specialists offers news you can use, with the latest on assessment tools, test interpretation, and approaches to individualizing care, including how to discuss lifestyle modifications and statin options. Learn when to suspect familial hypercholesterolemia, how to apply the concept of “cholesterol years,” and how to proceed when faced with differing guidelines on starting medication.
Thank you Erica. So um thank you all for being here and for the invitation. Um As you see, we are doing this talk uh in conjunction with our, the pharmacist and our care team um in the lipid clinic, we have seen that the management of these patients is greatly facilitated by having a pharmacist in the care team. So today, we're going to talk about lipid management in primary prevention patients um page. Would you like to introduce yourself? Sure. Yes, it's great to meet all of you. You may have received a message from me in the past. So, thanks for collaborating. If so, uh my name is Paige. I'm one of the pharmacists within the cardiology clinics. I work in general cardiology and also cardiac rehab right now, but definitely understand the primary care space. My previous role was a split role between primary care and cardiology. So hopefully, you can share some insight from my perspective and just look forward to collaborating with you all in the future. Excellent, awesome. So the learning objectives for today. So we hope by the end of the presentation, all of you will be able to describe the use of cardiovascular risk assessment tools, al and also the use of lipo protein biomarkers for primary prevention of A S CV D. We're not going to dive into secondary prevention but happy to discuss at a later date and then use of Coronary calcium scored to improve the risk prediction for A S CBD and personalized treatment including use of statins in primary care or primary prevention. Uh recognize the indication for use of different statins. Zia Belic acid are known as nex the P CS K nine inhibitors and then inc or leo in primary prevention patients describe approaches and treatment options in statin intolerant or statin adverse patients and how we utilize the Slco one B one genotype in clinical practice. And then lastly, hopefully understand the emerging role of pharmacists, pharmacy technicians, dieticians, and A PPS in the care team to improve care delivery adherence to these medications and then therapeutic lifestyle in inter interventions as well next time. So I will start by, by, oh, I'm reverberating here. Let me um can you hear me now? Oh, I can hear you. Perfect. OK. Thank you. I just have um feedback on my, on my, on my audio. So let me start by bringing your attention to um what is still the number one cause of death in the US. Despite our best efforts over time to get to zero heart attacks and strokes by implementing uh prevention measures in our patients. We are still um suffering from this uh burden of disease. So as you can see in this graph, the female uh cardiovascular deaths are in red in the on the red line and the male cardiovascular deaths in the blue line, we see a significant drop in cardiovascular deaths that occurred after we had a good understanding of the causes and risk factors for atherosclerotic cardiovascular disease. And we started implementing these broadly across the board for primary prevention and secondary prevention, we saw a quick and steady decline. This was also uh mainly due to a reduction in smoking improvement in hypertension control and um treatment of dyslipidemia. However, since 2010, where we got to the best um reduction in this um on these deaths, we are seeing a steady increase in cardiovascular deaths again and it seems related to the obesity epidemic that despite our best efforts, uh it's still uh growing in the United States and with it the burden of diabetes next slide. So we'll start by talking about what some of these commonly tested proteins and molecules are. I'll give you a brief lipidology overview to talk about um how we um treat these. So, lipids such as cholesterol and triglycerides are insoluble in plasma. So, the circulating lipids are carried in lipo proteins that transport the lipid to various tissues for energy use, lipid deposition and steroid hormone productions and bio formation. The cholesterol itself uh gets placed either in the incoming apo lipo proteins which are all shown here. They're called the apple B containing lipoproteins. When a lipo protein has a OB it will migrate inwards towards the body. And those um in um have different densities. The lowest density ones are the VLDLS and Kics kylo micros have a special apple B called B 48. All of the other ones have apple B 100 and these are recognized by the LDL receptor in the liver and taken up. So you have the very low density lipo proteins that mostly are going to transport your triglycerides. They also transport cholesterol. Then you're gonna have the intermediate density lipo proteins, the LDLs and then the LP Little lace that are very similar to LDLs but have this a attached to it that gives it special um properties to transport oxidized phospho lipids and cause badness. Then we have the HDL cholesterols that are all A O A containing. And we have, we know that there are at least 20 subspecies of HDL with various degrees of capacity to transport cholesterol out of the body. And it's called the reverse cholesterol transport. Next slide. So when um you have a dyslipidemia meaning a change in life of proteins that it causes adverse health consequences, they're called dyslipidemia. Um We have beyond the garden variety type, these familial forms um that familial hypercholesterolemia is the most common monogenic disorder and it affects about one in 250 people worldwide. It is caused by intrinsic defects in LDL metabolism. And here I listed or this, this table list the most three most frequent mutations, mutations in the LDL receptor where you have an defect, either in the LDL receptor production or the affinity of the LDL receptor for the ligand, which is apple B right. You can also have a defect in the apple bee itself. So it cannot bind to the LDL receptor. So you're just gonna have these lipoproteins floating around for much longer time and their excretion is limited. Then you have the P CS K nine uh mutations uh where a gain of function mutation might increase the degradation of your LDL receptors and knock them out of the liver surface and you cannot process your apple B containing lipo proteins and the levels are gonna be high. We suspect these um when we, the definition of familial hyper cholesterolemia um comes into your mind for sure when the LDL is above 1 90 mg per deciliter. However, there are people with lower levels. And uh right now in our clinic, we suspect familial hyper cholesterol leas with LDL above 1 60 plus a family history of premature coronary disease. Um Why are these important? It is estimated that at the same cholesterol level, let's say 1 90 or 1 70 in a person who has familial hyper cholesterol Leia compared to 1 70 of a non FH population, you will have three times the uh cardiovascular risk increase. If you compare it with normal epidemic populations, the risk is 20 times higher. Next slide. So this brings us to something that I really like to talk to uh patients about, which is the concept of cholesterol years. So, uh it is similar to the concept of exposure to any um any uh toxin uh such as exposure to uh tobacco. So we are very familiar with the concept of tobacco years. This is sort of the same in cholesterol years. So here you see the cumulative cholesterol years in the X axis and that dotted line with the circle around that blue box is the threshold for the onset of atherosclerotic cardiovascular disease. So be it an mi a stroke, cardiovascular death, peripheral vascular disease, all of these or aortic aneurysms. So when you have a patient with the highest cholesterol since birth, your onset of cardiovascular of atherosclerotic cardiovascular disease, your first clinical manifestation is gonna be very early uh while working with John and Mary Malloy, I met a uh twin um boys, 11 years old, one of the twins died of an acute M I at age 11. And um this is how dramatic this can be. Then when you have your moderate risk patients with hyper cholesterol starting from birth or a bad lifestyle that elevates your cholesterol from early on, you're gonna have um your curve turned down. And then if you have a lifelong low cholesterol, either you are one of those lucky people who just has low cholesterol because of their genetics or you have excellent lifestyle from birth, you're exercising and doing everything correct, you may never reach this threshold. So uh when you detect these elevations in cholesterol, you must ask yourself, how long has this been ongoing? Because it's not the same to have a 1 31 50 lifelong uh than a 1 50 that increased recently. Next slide. So when we're thinking about mechanisms um of atherosclerosis, I like to also inform my patients that there's three main mechanisms or three main things to think about as we treat these um conditions. So one, I always let them know that depends on what's in the soup. What I call the soup is how high are your apple bee containing lipo proteins in the blood? Um These especially the atherogenic type of proteins that carry oxidized phospho lipids and LDL are going to bind to the scavenger receptors, get under your endothelium and start this inflammatory response in your um and intima and then call more inflammatory cells in there. And you can detect this in the blood of your patients by um checking ac reactive protein which is downstream from the cytokine cascades that are pro inflammatory. So it's telling you are these cytokines activated or not, uh these can be um um reactant to any inflammatory process. But in general, if the CRP is below six, you're not thinking that there's, you know, an overt inflammatory condition in your patient. Just a marker of increased risk. Um I like to further refine um these inflammatory markers in my patients by uh um requesting what's called an LP PL A two, which I call my angry macrophage marker. And the reason is because this marker is secreted by the foam cell. So the microphage that is engulfed with these cholesterol ester has been unable to e flex that cholesterol back into the bloodstream to the HDL to carry it out and it just became sick and inflamed and is having a hard time. So LP PL 82 is my marker of vascular inflammation and sometimes these diverge in patients and I just like to have them to talk to them about, you know, improving lifestyle. The best anti-inflammatory that we know about is exercise. So it's pretty nice motivator to exercise. Um As I mentioned, my, my third component is the cholesterol E flux and this is not talked about much, but it is a very important factor for patients developing or not developing atherosclerotic cardiovascular disease. We've all heard, you know, of an uncle in the family who smoked and drank and had um horrible lifestyle. Lived to be 90 never had a stroke or a heart attack. Those people probably have an intrinsic, very good e flux capacity capacity to I would say heal their artery and take that cholesterol out, give it back to the HDL and not develop these plaques. In contrast, somebody might have a normal LDL of 90 80 horrible cholesterol efflux capacity um genetically or have developed this because an inflammatory condition because of diabetes, because of chronic kidney disease. So these things can vary throughout your life and it's, it's a balance right next slide. So how do we think of this today? So, I have brought in your first patient for today and um it is a 47 year old self identified white male patient who presents to your primary care clinic. He's had hypertension treated with isl 10 mg a day works a job. He says he's mostly sedentary lifestyle. He brings in his labs that include nonfasting lipid panel. And we see that his total cholesterol is 2 42. He's got an HDL that is not so bad at 51 triglycerides of 1 14 LDL calculated by the fried will equation of 1 68. And um you look at this cholesterol panel and you're starting to think, OK, that cholesterol looks a little bit high. He's got hypertension and then you talk to him a little bit more and his father had an M I at age 47 and that's why he's here. He's 47 years old. So he thinks, oh, I better get checked. His blood pressure is 1 33/70 so not perfectly controlled. And his BM I is 30 exam is otherwise normal. So um next slide um so our first um uh approach to this patient. And in any patient that presents to us for primary prevention of cardiovascular diseases is looking at lifestyle, discussing lifestyle with our patients. And in 2010, the American Heart Association defined this first, you know, set life simple seven approach. It was a new model and it um gave us an idea of what was important uh to discuss with our patients and what a good lifestyle meant. In 2022 the American Heart Association um recognized that it's not just exercise, diet, blood pressure control, having perfect lipids and body weight. But sleep sleep became a very important uh cornerstone of prevention and treatment. I can't tell you how many times patients have dyslipidemia due to sleep apnea or sleep sleep deprivation because they work two or three jobs. So it is a very important um uh metric uh ideal sleep is 7 to 9 hours per night. And I think, you know, I, I will not dwell into this, but I'm so glad the American Heart Association recognizes this now. So next slide, when we talk about these um lifestyle measures with our patients, they are usually pretty overwhelmed. You're giving them this huge to do list. So I always like to focus first on the things that we can change and the things that the patient feels more comfortable with doing. Um, a big one is usually tobacco if they smoke or um helping them with their blood pressure. Usually people are amenable to that, helping them with their lipids. And we'll talk more about that as well or with their blood glucose when they're in prediabetic or diabetic range. Of course. So when we're thinking about control of these risk factors, I always tell my patients, you know, they're additive. Each little thing that you do in each one of these categories adds up to your health. And so here we see a graph where zero is that dense uh bold line, right? No cardiovascular uh risk factors controlled the cumulative incidence of cardiovascular um disease increases, right? 45 almost 50% you manage one risk factor, it already came down about 10% and then they're additive each one. So this is all very good news to our patients and they don't feel so overwhelmed because they know that as soon as they control one, it's a big step down uh in the risk. Next slide. So in addition to recommending lifestyle changes, the big question, would you treat his cholesterol? So, next slide in um my clinic and I think most people think about, you know, balancing benefit and risks with your patients. And these are, you know, involved discussions that you um you think about the benefit is reducing heart attacks and strokes, peripheral vascular disease, decreasing morbidity, and very importantly, keeping patients active and independent well into their advanced age, improving life expectancy and quality of life. The risks of course, of side effects of these medications cost patient comfort and willingness to be on prescription medication. Some people need a lot of hand holding and more than that a lot of information and um, just understanding what is it that we are trying to achieve next slide. So let's look at the guidelines for recommendations on our next steps. So, in your patient who came in, um, the calculated 10 year A S CBD risk score came uh out to be 7.8% right? These are called the pool cohort equations. We get them in apex pretty quickly. I just type dot A CBD and pick the, the golf equation and apex calculates it for me. So in him, uh it's 7.8% which is above 7.5. Um I'm gonna walk you a little bit through these different guidelines because who do we listen to? There's a lot of information out there and different cutoffs, different um uh uh A national uh guidelines, the American Heart Association AC C guidelines were the guidelines that came from the NIH guidelines. So the NIH started um their guidelines system or pretty early on trying to drive consensus for treatment. Um and then the A H A and AC C took over. Uh then NHL B I had other things to think about. And so the American Heart Association and American College of Cardiology carried on with the guidelines from them. They are, I would say the guidelines that we like to follow more. Um They are frequently updated. The most frequent, uh the most uh recent update was 2019. These guidelines call for screening every 4 to 6 years and we started at around age 20. Um That doesn't mean you're not gonna screen people earlier if they have a strong family history, like kids from families with. Um, we use these pool cohort equations to estimate 10 year risk of heart attack stroke and a cardiovascular death. If the LDL is between 71 89 um the guideline uh encourages you, I would say or says that in this population above 7.5% the benefit of statin is favorable to for your patient. So when you take these equations and then um for anybody who is between five and 7.5 so above five is considered a moderate risk below five. low risk, you would do a one on one talk with your patient and we're gonna talk a lot um more about that. The US preventative um task Force service, um calls for um prevention starting at age 40 to 75 years and they're more strict on their definition. They require, you know, random controlled trials for their recommendations. So they're much more strict. If your risk is above 10% and at least one additional risk factor, then they ask you to consider to offer a low to moderate intensity stat. Next slide, there's also the United States va Department of Defense guidelines. The most recent one in 2020 where you start screening above age 40. And then these are also a step up. If your 10 year risk is more than 12% they recommend a moderate intensity statin. If you're 6 to 12% you consider discussion of statin initiation and then the National lipid Association, which is a newer, um, a new or uh new or one of these medical associations is more broad, uh consider lipid analysis on those over 20 years old. And um the treatment is based on risk and it gives us targets for non HDL cholesterol as well as LDL. Um, we kind of grandfathered in the LDL cholesterol as a risk marker. Uh stemming from the Framingham Heart Studies um in Europe and other parts of the world, they use much more the non HDL cholesterol. So in general, non HDL cholesterol um is 30 mg per deciliter higher than your LDL. Unless you have hypertriglyceridemia, it's gonna go further on next slide. So, um, we will, you will have access to these slides to look at these in more detail if you're interested. But these are the National Lipid Association guidelines that define low, moderate, high and very high risk, very high risk. Is anybody with established heart disease? A CBD or diabetes? Oh. Mhm. Your blow hunt. They like to um, have people go below 70 which is what the American Heart Association and AC C also like to have you uh in, in very high risk patients we use in our lipid clinic, the European guidelines for people with established coronary disease and, and high risk. We like to go below 55 because from score trials, we know that there might be more sustained plaque regression and reduced um progression of disease when your LDLs are below 60. So we like the 55 uh goal and you'll see maybe some of your patients that we write that in the, in the clinic nodes, a name for that. So who do you listen to? Um There, like I mentioned, there are various guidelines and it's different also elsewhere. So next slide, what I often just recommend um next slide is to just keep calm and choose one. You can practice at any one of these levels that you feel comfortable. Um You have a discussion with your patients and see what their level of comfort is. Some people want no risk of coronary artery disease, stroke or heart attack. Some people feel comfortable with having, you know, a lifetime risk of 39% which is like the threshold for treatment. Um So it is a 1 to 1 basis for me. I want no heart attacks and no strokes. So I would consider myself a pretty aggressive practitioner. As long as I keep my patients safe with the avoiding side effects, I think we have a good understanding and, and I follow the patient, um uh wishes and how they like to proceed. Um So next slide, what do these have in common? They all endorse the use of statins for primary prevention because they're cheap, they're effective. They have low uh side effects and in general, they're all risk based. So you stratify the risk of your patient, get to know your patients well, establish if it's been a long lifelong high cholesterol, you're gonna be much more aggressive if this patient has never gotten treated. Um because they've already accumulated exposure, right? And um rather than targeting a specific LDL level, um you're gonna have a, a discussion with your patient of what is the overall goal next slide. Um The American Heart Association also helps us by defining these risk enhancing factors um to help you decide who is at higher risk, right? Because the higher the risk, the more likely you are to give them um or offer treatment. Anybody with a family history of early onset heart disease, anybody with these LDLs above 1 60 chronic kidney disease metabolic syndrome. And I really like that the American Heart Association defined these women specific guidelines. Now, in all of our patients, female patients, we should ask for pregnancy complications. We know that women who had pre clams, who had gestational diabetes, who had um a premature baby or small for gestational age are at increased risk of developing um heart um atherosclerotic cardiovascular disease or complications. Um Well, beyond their post menopausal years. So, it is important. Also chronic inflammatory conditions are also more common in women such as lupus rheumatoid arthritis and um also psoriasis. Um als, there's also an importance to um take consideration into your high risk um race and ethnicities. Uh South Asians are have guidelines of their own. They're considered overweight at a and um there's waist circumference, this are lower thresholds to be considered metabolic, uh metabolically, abnormal fat depositions. So these are uh ethnicities. Uh South Asians need to be treated more aggressively and considered a higher risk. Next slide, we also uh were given these biomarkers to think about um from the guidelines, the most recent guidelines to consider um initiation of treatment, right. So anybody who has elevated triglycerides above 1 75 is considered higher risk because you have um combined hyperlipidemia that are going to be more, more atherogenic. One of the most atherogenic profiles you can have other than A H are elevated VLDL, um small den cell DLS and those are all due to these metabolic disorders that elevate triglycerides. High sensitivity CRP is above two LP little A I think we could um potentially come back to discuss it. Um is a, I would say more novel, very well established risk factor by now for developing enhancing A S CV D risk or A S CBD um progression and aortic stenosis apple be above 1 30 acre indexes below 0.9. All Right. So, next slide now um I'm gonna hand it over to page um page, please. Uh take it away and what do we do now that we have um these things in mind? For sure. Thanks doctor. So, so we have all these risk factors. But why are we still focusing on LDL targets and lowering of cholesterol? And what do we use to guide our therapy and make these personalized decisions? Next slide? So I love this uh chart here and I think it's super helpful, maybe a little bit complex to show your patients, but definitely important for them to understand. So just so that you're aware, this is showing about uh 14 different trials showing that present reduction in LDL cholesterol is indeed providing benefit to the patient even if not able to achieve their goal. So the LDL cholesterol or LDLC hypothesis is the concept that elevated LDL is a main risk factor in the development of atherosclerosis and then ultimately cardiovascular diseases. So just to orient you here, you can see the reduction in LDL cholesterol is listed as minimal per liter. But one thing to note that equals about 38 mg per deciliter, which is how our LDL is reported out to us. So if you look here, um one important thing, if you look on the left hand side, that shows the reduction in the vascular events in terms of a percentage. So let's say your patient um goes from one millimoles per liter down to 0.5 millimoles per liter. So very small change, you can see that the percent reduction is very significant. And this is really helpful in patients, let's say their LDL was 1 38 and we have a target goal. It be less than 70 or less than 55 for them. And they're getting to 100 on a statin that their um tolerable dose and they might get frustrated and say the statin isn't working. I don't understand but explaining to them that we're still reducing events, even if we're not necessarily getting to goal and that we have other options is really helpful for patients to continue on the medication. And then ultimately think about some other options as well. Next slide. So now that we have introduced you to our patient, let's dive more into the primary prevention guidelines and how you treat each of your patients with statin and then the other medicine options that we have. Next. So we have three specific patient subgroups which are listed here on the screen. So if patients like doctor stack men come to you and they already have this baseline LDL. That's greater than or equal to 1 90 they fall into one category if they have diabetes, which is likely a lot of your patients in primary care, but their LDL is less than 1 90 they're still in another bucket. And then the third bucket would be those patients who don't have diabetes, but their baseline LDL is somewhere between that 70 to 100 and 89 mark. Next slide. So we'll go through these a little bit further in detail. These charts are from one of my favorite resources called Pearls. I think it's super helpful. Um And sometimes I even share these charts with patients, especially the knowledgeable patients so that they can understand what's guiding treatment. So these will be here for a resource for you, but let's just walk through them quickly. So this first is that group that they come to you and their LDL is greater than 1 90. So taking into consideration is if this is the only thing that you know about them, we haven't tested those other biomarkers quite yet or we don't have a coronary artery calcium score, but we know their baseline LDL. This is what we would consider. So we would first want to get them on a maximally tolerated statin whatever that means for the specific patient. And the target LDL goal in these patients would be at least less than 100 you'll see a little bit later on on maybe where we would change that goal for these patients. Um But that's where we would first start next slide and then this is the patients with diabetes. So likely lots of your patients. And one thing to take into consideration here is there's also diabetes specific risk enhancer. So not only LP little A AOB the CRP that we discussed. But there's these factors that if patients have diabetes also put them at high, high risk. So some of them include if they have retinopathy or neuropathy, if their urine albene ratio is greater than or equal to 30 their GFR is less than 60. And then one thing that's interesting is they do differentiate between type one and type two, the duration that they've had this diagnosis of diabetes. So the first thing we still want to do in all of these patients is calculate that 10 year A S CBD risk. If they fall into that 40 to 75 age range, obviously, if they're younger or a little bit older, that's where it becomes more of a patient clinician specific decision. But we still calculate that risk. And if their risk is greater than or equal to 77.5% we always want those patients if they're able to tolerate on a high intensity statin, if their risk is lower than 7.5% we would consider more of a moderate intensity statin and then kind of trickle down in terms of alternate agents. Next slide. And then our last group is kind of where we would consider our patient to fall into here. So this is adults without diabetes and their baseline LDL is 70 to 100 and 89. So very similar approach to the previous slide where we always want to calculate that 10 year A S CV D risk to see where they fall here. So let's just um take, for example, our patients. So it would be um in that middle column 40 to 75. And then the third kind of peach colored blurb that says greater than equal to 7.5% all the way up to less than 20%. We would consider a moderate intensity statin for this patient and an LDL goal of less than 100. And then I want you to look down below to remember this chart if you can, when we talk a little bit more about a coronary artery calcium score. So let's say this patient, we, we have the information we know about them. We're wanting to target a goal of less than 100. But we have another tool that we're able to utilize that doctor stock will talk more about and that's the coronary artery calcium score. So if you look below in that bottom box and just remember that third section here where um it says a coronary artery calcium score of greater than or equal to 100. And you can kind of follow that to the right and see that that LDL goal does indeed change from what we previously thought of less than 100 to now, less than 70 next slide. Thank you, Paige. Um So as Paige mentioned, um in primary prevention, we um we have extra tools this graph here is just here to show you that using the pool cohort equation to calculate the risk score with your patient is a class one indication, putting them on lifestyle um changes uh to reduce their cardiovascular risk is also class one indication. Now, uh the risk enhancing um factors in the coronary calcium that are adjuvant. So you can make a better informed decision with your patient. They're plus to a indications next slide as we go back to our patient, would you treat his cholesterol? So his 10 year A S CV D risk score is 7.8 per the pooled equation and further work up revealed no additional risk factors or risk enhancer. So, per the American Heart Association A H A guidelines, you would consider a treatment given that his risk is right there above 7.5% and his LDL cholesterol is above 1 60. But per the other guidelines that we discussed, you would not consider treatment. So what if um let's see the next slide, your patient decides to do a coronary calcium score or you uh recommend to do one in general. Uh and this is his coronary calcium. So here you see um that there are at least two territories with coronary calcium. This is not this patient, this is probably a higher calcium score, but I just wanted to show you what it looks like and this is something you can look at with your patient in the office and show them the calcium as Paige mentioned above 100 is the guidelines um I won't get too deep into coronary calcium s course. Next slide. Um We have, I am a co-chair of the right care initiative of the Bay Area and we have a full program on Monday with Matt Budo. Um talking about the use of coronary calcium score. If you're interested, I'll send you all that link for Monday. But in general, we use it in people um who are moderate risk who want to have a more in depth discussion of their risk. You demonstrate the end point which is the presence or absence of established uh plaque. You can do that with a carotid ultrasound and very young patients who are likely not calcified yet. Uh U CS F doesn't do carotid inter thickness. So it's not something that we use routinely. Um The other great use for your coronary calcium scores is the, you know, older patients who um whose risk is mostly given um the number by their age. If they're healthy, you can do a coronary calcium score to skip the statin. They might have a calculated risk of 15, 20. And you're thinking this patient looks great. No hypertension, normal sugar exercises. Eats well. Why should they be in a statin? You do a calcium score and it's low, you can skip the statin. Um next slide back to our patients. So once you have these coronary calcium score numbers. You can go back to the mesa databases and plug in these coronary calcium score and and get a revised cardiovascular risk. So about more than 50% of your risk estimates are gonna move up or down. Once you have these coronary calcium scores, there's also a pretty wicked um app that calculates your um your vascular age and people get very upset or very motivated depending on the on the personality of your patient, when you tell them that they have the arteries of an 80 year old. So use that one with caution um for this patient, his estimated arterial age is 77 years old. So with that in mind, we favor treating with a moderate to high risk next slide. Perfect. Thanks doctor. So how do we start now? So what do we do when we monitor these patients? And how often do we assess the patient's response? Next slide. This is a little busy of a slide but just included for a resource for you all. So typically we always want to have a baseline lipid panel and sometimes in our patients, we consider a baseline CK as well as liver function tests A one C and as we've mentioned a couple of times that LP little A after we start treatment monitoring LFT SI know this was previously done a lot. It's not currently recommended unless they were elevated at baseline. And one thing to know is if you have patients who have stable chronic liver disease, they may be nervous to start a statin medication. But as of right now, we don't need to avoid the medication in that class and that's where we can have a lot of education with our patients. Now, if you check the LFTs and they're elevated at baseline, and you're considering potentially using A P CS K nine in the future, like repatha or you should really check a lissom acid lipase activity in order to rule out that cholesterol storage disease, which we do have specific treatments. For typical approach is if we start a statin, the patients experience this musculoskeletal pain will hold the statin sometimes check the CK and then um that sometimes makes patients feel a little bit better if their CK is normal. But again, these are all tools that we can use on a patient specific specific um scenario and then obviously assessing adherence and um the patient's response to these medications as well as lifestyle intervention. So a lot of times we work really closely with our dietician about 4 to 12 weeks after starting a new medicine. Or if we make a dose adjustment, we typically go in that 8 to 12 week mark within our clinic. And then depending on where they're at, if they're at goal or if they're not at goal, then we change the frequency of monitoring based on that next slide. So let's dive into the statins next slide. Who here has heard of the nocebo effect anybody nobody. Ok. So the placebo effect um can be measured in the same way as the placebo effect. So think of it when members of a control group receiving an inert substance report, a worsening of symptoms nullifying the placebo effect by simply having a negative attitude towards the effectiveness of the substance prescribed. So this is very common among the statins and something to take into consideration when you're meeting with patients or having the statin discussion to start next slide. Perfect. So, statins are still considered the cornerstone of pharmacological therapy. Among the available lipid lowering medications, we have statin intensities, low, moderate or high, but I really um try to avoid using the word intensity with patients in the clinic. I think it kind of makes them nervous when we say the word high intensity. So more. So we try to um educate them that we see different lowering of LDL with different types of statins and they're not all the same um if patients are at higher risk. Um we also sometimes use that Slco one B one genotype to help make a decision. It's not perfect, but it is a tool which tells if they have some sort of decreased transporter function. So let's say we assess their risk, we think they should have a high statin, they're very nervous. Sometimes we can utilize this to make them more comfortable um with the decision to start and then also one thing to note is currently the only statin that is brand name is Peta Statin or Lavalo, but that will be generic at the end of the year. So hopefully we won't have cost to become an issue with any of the options if we choose to use that specific one next slide. So I love this statins comparison slide and I often will even share this with patients, I think for a long time, um The statins had a negative um view within the public where we hear a lot of misinformation around the statins. And one thing to note is not all statins are created equal. So they're all very different and we'll dive a little bit more into that a bit here. But it's important to take into consideration some of these um other factors. So if you look at the top of this slide, you can see dose timing, um taking with food grapefruit and then myopathy risk a lot of times or in the past, um medication label at the pharmacy automatically said all statins need to be taken at bedtime. And when you look at certain data, remembering to take a bedtime medications in certain patients is actually very difficult. And so that could have been a reason the patient wasn't adherent to their medication. And so if you look here, there actually are statins and quite a few of them actually that you can take any time of the day and they're still effective for patients. So if you have a patient who you don't think will remember their bedtime medication, but they'll remember their morning medicine that will allow you to pick a specific statin. And then another thing to take into consideration is the myopathy risk. So, depending, and we'll talk about this in a couple of slides of the hydrophil electricity of the statins, it can affect the risk of myopathy. And so even showing them and showing them that we're very low for certain statins sometimes makes them more confident and comfortable in starting the medication. Another thing to consider a lot of people will bring up the grapefruit juice because they've heard of that and not all of the statins actually have that while we typically don't think even like um a small amount of grapefruit juice is really harmful if they love grapefruit juice and they're so worried about it. There are certain statins that really the interaction doesn't exist. So it's just some things to take into consideration when you're picking the one for your specific patient next slide. So while we would hope that patients don't experience these statins associated muscle symptoms, some patients do indeed have these side effects. So they typically present a subjective myalgia and about 5 to 20% to report this effect observation, it is indeed rare for those more severe muscle breakdown um to occur in patients such as Rabal. Although I have seen it in one specific patient and when they were discharged from the hospital. So it does happen, it is just very rare and then some predisposing factors to take into consideration if your patients potentially could be at a higher risk are listed here. So if they're female, if they have a low BM I Asian ancestry have excessive alcohol consumption and some of the other high risk medications and or comorbidities would be things to consider. Um So the statin associated side effects here are listed and um this is more for a resource for you. So again, the myo so we check that kind to determine if um it's a myopathy or rays is present and then also a lot of patients will come to you and say that I've heard, I don't want to take a stent and it's going to give me diabetes and while statins can increase the risk of new onset diabetes, especially in those with risk factors. So, such as metabolic syndrome, if they have a BM I over 30 or if they're already in that prediabetes phase where their A one C is above 6%. Um The current guidelines currently state that this should not be um a reason to discontinue the statin or not start the statin. But obviously having those conversations, like we mentioned earlier and educating the patient, we already want to decrease those other risk factors to decrease their over cardio overall cardiovascular risk sometimes helps. And then again, just here on the liver function tests. So we typically don't always check them afterwards because it can kind of freak people out if you get a transient increase in your LFTs. But if it's not greater than three times the upper limit, it is indeed safe to continue the medicine next slide. So I love this slide. I think it's really helpful and important um when treating specific patients. So patients who experience those statin associated muscle symptoms may be able to tolerate a re challenge with a different statin or an alternate regimen. So as clinicians, we should always be reassessing rediscussing and re challenging whenever absolutely possible. As long as the side effects are not severe, um after we discontinue one agent and we see resolution of symptoms, we can consider trying a lower dose of a medication, an alternate statin that's preferably metabolized via a different pathway. Or here on the slide, here has a different hydrophilic and then we can also consider alternative dosing regimens such as every other day um or things like that. So, on this slide here, you can see there's two specific hydrophilic statins, reat and pravastatin. Uh those two medications are thought to penetrate the muscle to a less effect compared to the lipophilic statins, which are listed on the right hand side of the screen. It is helpful to know though that pitavastatin or Lovallo, even though it is a lipophilic statin does have a very low myopathy risk and sometimes we do utilize that in our patients. Our typical rule of thumb or my typical rule of thumb when I meet with patients and I always educate them is prior to saying their statin dose is zero. We should really um at a minimum try two, preferably three statins. I always say three statins, two hydrophilic um statins. Before we would say, OK, you really don't tolerate statins or maybe they had the SOCO one B one with multiple showing decreased transporter function. And I think explaining to patients that they're very different statins, I've gotten multiple patients who were previously saying I don't wanna do any statins actually be willing to try a lower dose statin or this alternate regimen option. Next slide. This is another um description of how the metabolism of statins are different. So if you think back to, you might have used the Liverpool interaction checker when all of our patients were prescribed packs Ovid. And we were trying to understand if we should stop statins or what we should do. And as they, we learned more, those got updated depending on the specific statin and they were different and that has to do with the sip um type of interaction. So as you can see here, the different statins interact with the sip enzymes a little bit different differently which potentially like let's say they're on certain other specific medications. This may allow you to make a decision that doesn't interact with their current regimen quite as much. Um And so one thing to note um in the middle to the PP GP just is an e flux transporter located in the gut mucosa and regulates absorption of certain drugs. So, if patients are on those types of medications, we should look into some of these other statins that wouldn't have an effect there. Next slide and then just touching on briefly um statins in pregnancy. So in 2021 the FDA requested removal of the pregnancy category X label for statins. At first, this um left us kind of with little data to make clinical decisions and we were not sure exactly what to do, but we've since received some information. And so in most patients, we should still be discontinuing statins in pregnant patients, but it is OK to continue during the family planning stage. Uh and we should consider continuing in patients who are at high risk um during pregnancy. So those who have had previous A S CBD or Homozygous FH and currently they say pravastatin would likely be the best option in those patients. Next slide. Yeah, so we'll leave these here. I think um the main thing um would just be these additional agents. I think this slide is the most helpful here showing that there's um it's a couple of slides up with the graph. Perfect. So they went back. Yeah. So these are the additional agents mechanism of action. So you can look at this and see um how they inhibit the production of statin or inhibit the production of cholesterol such as statins or beed do acid Belic acid is neo. It's the newer medicine that's the closest in terms of mechanism of action to statins. And then if we think of Zia and the P CS K nine, the Zia works in the small intestine and then the P CS K nine helps to prevent the destruction of the receptors that remove LDL leading to more LDL getting removed from the blood. And then the next slide, one thing to note is this is helpful to make a personalized decision to better understand what percent lowering of LDL do we see with these agents. And so as you can see, Zia has a lower percent reduction in LDL compared to the P CS K nine. So if you need more than just 18% to get to goal, it may be appropriate to utilize the P CS K nine in that specific um scenario. And those medications, we have really good luck getting them covered for patients. Oftentimes they do require a P A. Um but uh we have a pharmacy technician who helps with that in our clinic as well as those other grants and patient assistance programs that we can utilize. And so just because it's an injection, we can have the conversation with patients. And um we have a lot of patients on those within our clinic
