Dr. Harpreet Bhatia provides primary and secondary prevention and guidelines for cardiovascular disease.
we have with us today. Dr Harpreet Bhatia. I'm so happy to have him here. Um He is a post doctoral research fellow with the integrated cardiovascular epidemiology fellowship at U. C. S. D. Right next door to us. Um He's also currently pursuing a master's including research at UcsD. His clinical and research interests include preventative cardiology and general cardiology. Including lipid disorders specifically lipoprotein. Little A and oxidized foster lipids and primary prevention risk assessment. Um I'm so glad to have another cardiologist here amongst us. Endocrinologist to really give us a different view on this and you're really an expert in this field, Harpreet, thank you so much for joining us. Take it away. Thank you so much for for having me. I'm excited to be here and this is a topic that I'm very interested in both clinically and in in terms of research and these are my disclosures which aren't relevant to this talk. I'm going to start with a case just to kind of frame the discussion of what we'll be talking about in the next half hour. Um So it's a 55 year old caucasian woman with a history of type two diabetes has had type two diabetes for 11 years and a one c. Of 6.1%. Currently hypertension, chronic kidney disease with the G. F. R. 45 no prior atherosclerotic cardiovascular disease or A. S. C. B. D. And she's a nonsmoker in clinic. Her blood pressure is 1 40/85 total cholesterol is 1 70 th deals 40 LDL is 1 10 and triglycerides are 100 and the question be posed to you is uh in addition to lifestyle modifications which we recommend to everyone. What would you recommend for therapy for primary prevention of cardiovascular events? And the options in the context of this discussion would be a moderate intensity statin plus or minus aspirin, high intensity statin plus or minus aspirin or aspirin alone. We'll come back to this after we kind of go through the talk and cover some of the points here. So the outline for this talk is we'll start with just discussing a little bit about risk assessment briefly and then go into talks on lipid management and anti platelet therapy. I'm breaking both of those up into secondary and primary prevention and I'll be covering secondary prevention first for both of those topics. I think it's uh pretty much it's a more straightforward topic than primary prevention. And there's more of the data I think is informative and the primary prevention literature. And we'll also discuss how the A. D. A. And A. C. Ch. A guidelines all line up with each other. This is just a quick slide on why this matters and I think everyone probably knows how important this is among diabetic patients. But S CBD is the leading cause of morbidity and mortality in diabetics and it's really important to control cardiovascular risk factors. In addition to treating their diabetes. And in particular adults who at age 40 to 75 which has become kind of a magic number. And a lot of the guidelines with diabetes are predominantly intermediate to high risk of a first S. CVD event. And so they're elevated risk compared to the general population. And when people who are diabetic have a first event they tend to have higher morbidity and mortality from that event. So it makes it even more important that we work to try to prevent that first event. Let's talk a little bit about risk assessment. And nowadays the CVD risk calculator which was developed by the A. C. C. NH. A. Based on something called the pooled chords equation has basically become the standard of care for risk assessment for cardiovascular disease. And it's a primary prevention tool. Its main role is in primary prevention and the A. C. C. H. A. In general recommended for all adults who are at least 40 years old up to 75. And based on that risk calculator which I'll show in a moment. You can classify a patient's risk and it helps inform their lipid management. You can be classified as low risk borderline risk, intermediate or high risk and helps inform kind of what their therapies uh therapies might be appropriate for them. The sort of borderline to intermediate risk I think are the most important categories. Um The high risk. It's generally pretty clear I think what to do with them and low risk is also more clear. But in this borderline intermediate risk category can be a little bit more murky on what therapies are appropriate for what patients. And because of that, the guidelines do also endorse coronary artery calcium scoring as a potential tool in this sort of middle region to help re stratify people when there is some uncertainty about how to best treat them. And I'll talk a little bit more about that as well. And this calculator has been endorsed by the american diabetes Association and has been studied and validated in diabetics as well. This is what it looks like. So there's a website where you can just plug in these demographic variables. You can also get an app on your phone. But essentially it boils down to really nine variables, demographics of sex, age and race. Um some basic labs so their total cholesterol and HDL cholesterol and then there's systolic blood pressure and then history of diabetes smoking or treatment for hypertension. And for example, if we plugged in the patient presented in the case earlier, you would get a 10 year risk labeled there at the top 10 year a. S. CVD risk of 6.9% which would put this patient in the sort of borderline risk category. And we'll talk more about that. And you also get this lifetime er sort of 30 year Risk which is 50% in this patient given that she's only 55 years old. That can be a significant consideration to start with lipid management and I'll start primarily with secondary prevention. A quick note on lifestyle interventions. I think this is something that's going to be well covered um in other places. But lifestyle interventions are obviously recommended for everyone um that we're gonna be talking about. And I do want to note that the mediterranean and dash diets or the diets that are specifically endorsed by most of the guidelines. And in terms of lipid monitoring, the guidelines give kind of these complicated different scenarios of lipid monitoring. Essentially everyone with diabetes should have a lipid profile checked the first time you see them, the first time they're diagnosed with diabetes and at a minimum every five years thereafter. But really a lot of these patients are going to be on lipid lowering therapy and they should be checked annually Whenever there's a dosage adjustment or starting a statin medication uh lipid profile should be monitored for the response to that. Which can be 4-12 weeks after initiation or a change in dose. And we're talking here predominantly about moderate and high intensity statins. There really is not a role for anything below a moderate intensity statin. The only scenario where you would put someone on a low intensity statin, ideally would be if they just don't tolerate higher dose of statin. But ideally we're talking about moderate and high intensity statins and moderate intensity stands are estimated to achieve LDL lowering of 30 to 49%. And the most common ones these days are atorvastatin 10 to 20 mg and resurfaced in 5 to 10 mg. And then for high intensity stand therapy that's estimated to lower the LDL by over 50%. And again talking about higher doses of atorvastatin in which she was datin predominantly in terms of the cardiology society guidelines to give sort of this complicated flow chart on secondary prevention starting with clinical S. C. V. D. And then as I mentioned everyone should be given counseling on lifestyle modification And then they break up patients based on their risk in their age. And we'll try to simplify this a little bit here and also try to line it up with with what the A. D. A. Guidelines say. And for the most part of the A. D. A. Guidelines and the A. C. C. H. A. Guidelines are pretty much in sync I think for all the high points they are basically the same. There are some small nuances here and there. Um And we can kind of synthesize the two together I think. Um So both guideline groups would recommend a high intensity statin for anyone who is secondary CVD prevention. So that's pretty straightforward high intensity statin or at least maximally tolerated statin is what's recommended. The cardiovascular society guidelines go a little bit further by giving a goal reduction in LDL of 50% and really the target there is to try to get the LDL less than 70. And uh if the LDL is above 70 then there is endorsement of using a set um are um in this group of patients to try to get the LDL lower. Then both guidelines have this sort of elevated category of a very high risk patient who's uh which I'll get to on the next page. Um and there in that group, the A. D. A. Does adopt the target LDL goal of less than 70. And then additional therapy as needed, which could be, is that um I've or this very high risk category opens up the option of a PCSK nine inhibitor in both groups. Yeah. And then age over 75 is another common theme in the guy lens. I think historically this has been an area of a little more controversy or less certainty. Um partly because this is not a group that's well studied in any trials really. However, it's a group that given their age tends to be higher risk than other groups and actually more likely to benefit from statins. So both societies give basically a recommendation to individualized to the patient balance risk and benefits, but it's endorses reasonable to initiate or continue a statement with a stronger recommendation to continue a stand in this patient population and we'll talk a little bit more about why maybe there's historically some hesitancy there and then in terms of very high risk what elevates people to that category where the A. D. A. Would definitely recommend the goal of LDL less than 70 and where in addition to his enemy PCSK nine inhibitors become an option. It's based on this pretty straightforward table. And to be very high risk patients have to have multiple major S. CVD events or one major S CVD events and a. B. C. D. Event and multiple high risk conditions. So major s. CVD events are essentially a history of M. I. or stroke or symptomatic peripheral arterial disease. And then if there's recent acute coronary syndrome within the past 12 months that's kind of an additional event. Um And then in terms of high risk conditions you can see highlighted their diabetes is one of them. So if someone has diabetes they have had a history of an M. I. And then they have any additional risk factor that's listed here like older age hypertension. Ckd smoking, they're automatically in that very high risk category and would have a target LDL S. And 70. And both guideline groups. A quick note on other lipid recommendations um In general statins really are the therapy and um is that it might in PCSK nine inhibitors or then the next line on top of statins uh fi braids and niacin in addition to stands are not recommended in either a guideline and a note on triglycerides because this is something that is sort of a hot topic and it is evolving in the literature and is making it now into the guidelines um sort of this bottom group here with people with S. C. V. D. Who have a well controlled LDL on statins but still have persistently elevated triglycerides. There's an evolving role now for omega three fatty acids. Um This is based on the reduced trial which showed a reduction in events um in such a patient population. It's important to note that that was on a specific formulation of omega three fatty acids called acosta, pen ethel. This does not apply to all Omega three fatty acids that may have different mechanisms. And the other thing to note is this this is I think being adopted in practice but the uptake is uh it will take time and I think part of it is there were some concerns in the trial is about control groups and things like that. But I think this is an area that's going to be a further study and I think we'll be further elucidated with time. So now on to primary prevention for look at management. Again there's this complicated diagram in the cardiovascular society guidelines and this long pathway. But basically if someone has diabetes they just divert from this pathway and exit at this top right category here. And so we'll simplify this again again for both guideline group status for the therapy of choice for primary prevention and then beyond that the groups both breakdown patients based on their age and a lot of this is based on really what's studied. Um So age 40 to 75. Again is this kind of magic number of just what studied a lot in trials and the minimum for all these patients is a moderate intensity statin or again, maximum tolerated up to that point, but really moderate intensity statin. The guidelines then give sort of criteria for what makes someone higher risk. And we'll talk about there's some diabetes specific risk factors on the next slide, but age 50 to 70 counts as one of those risk factors. So a huge chunk of this population is already considered higher risk. And at that point you aim for a high intensity statin In the cardiovascular society guidelines. You aggressively target and LDL reduction of 50%. Which again is what you hope to accomplish with the high intensity stand For age 20-39. If there is a presence of any of these risk factors that I'll talk about, a statin is considered a reasonable thing to start. And then again, age over 75. It's similar to the secondary prevention guidelines where it's individualized to the patient, but it's definitely not discouraged to put someone on the stand. And finally, the SCV. D. If they have an A F A. S. C. B. D. 10 year risk over 20%. It's reasonable to add on is that in my in addition to statin to try to get there. All the all reduced by at least 50%. And this is kind of one of the only places where there's a specific number from the S CVD risk score in terms of diabetics. Um a lot of those numbers have kind of been done away with in terms of guidelines for the diabetics, just because diabetics are considered kind of at higher risk at baseline to put this whole thing together, essentially I would take it as you're going to try to put most diabetics on at least a moderate intensity statin unless they really are just a low risk younger patients. And you basically look for a reason to put them on a high intensity statins. There's not a lot of studies of high intensity stands in diabetics, which I think is why the guidelines don't give a blanket recommendation for high intensity statins in this population. But they do mention sort of in the text that are guidelines that they really encourage high intensity statins and you kind of just have to look for a risk factor or even as a gin creases to put them on a high intensity statin. And these are some of the risk factors that would push towards a higher intensity seven having diabetes for a longer time having album honoria or CKD retinopathy neuropathy or an ankle brachial index less than 0.9. Again, this is going to capture, I think a lot of patients in that 40 to 75 group or even potentially in the 20 to 39 Age group with type one diabetes. So uh it's really I think um kind of encouraging high intensity statin use and really just looking for a reason to put someone on a high intensity stand. And this is some of the data that sort of backs up standing use in diabetics. This is from primary prevention studies for trials of diabetics and this is in this meta analysis, there was a 25% reduction in cardiovascular and cerebral vascular events. And then that benefit was seen in M. I. And stroke as well in this sort of primary prevention population. So we know stands work in primary prevention in diabetes and this is uh some figures from the cardio trial cards trial where they randomized patients with the tourists and or placebo diabetic patients in primary prevention. And saw a significant reduction in events. But what's important to note is for this trial, the mean LDL was about 1 15 in the trial and when they separated by above and below that mean level, there was no difference in the effect of statins in this population which is why sort of we've moved away from a lot of sort of LDL cutoffs and things like that from when to start. Um statins in these patients. And there are other trials like this to basically suggest diabetics benefit from statins regardless of their initial risk or LDL level. What about risks of statins. Um it's definitely a consideration especially in primary prevention because you have to balance the risks with the benefits more as the benefits are going to be lower in primary prevention. This is a meta analysis of 13 trials that included diabetic patients With statin use and there was a nine increased risk of incident diabetes in this meta analysis. Um to put that in context, it's basically 255 patients would have to be treated to produce one event of diabetes. However, for that same population over five events, cardiovascular events would be prevented. So, the benefit of sand still far out weights. This risk. This is again an evolving field. As I was putting together these slides, a paper came out in Jama Internal Medicine about a week or two ago showing that in a population of veterans and a retrospective study that patients who are already diabetic and put on stands may have progression of their diabetes and it may just be a signal that these patients need to be monitored closely. But again, it appears over all the benefit of stands outweighs the risk for the sake of time. I won't spend too much time on this uh cognitive function element other than to say, the the preponderance of the evidence is that stands do not reduce cognitive function in elderly patients. And I think as I alluded to before, this has historically been part of the hesitance to put elderly patients on statins. But the data hasn't worn it out even on statins that cross the blood brain barrier. So let's move on now to aspirin to synthesize both the secondary prevent primary prevention guidelines. The secondary prevention guidelines are very straightforward. If someone has that S. C. V. D. They should be on low dose aspirin indefinitely. Are the only reason to take them off would be if they have a lot of bleeding events or significant bleeding risk. But really this is a population there's clear benefit long term for low dose aspirin and then there's evolving data that's I think not fully adopted into clinical practice yet. But it is going to be more discussed is putting people on a oral anticoagulant. In addition to aspirin based on a couple of different studies. But I'm not going to talk too much about that today. So I really want to focus on primary prevention for aspirin because this is the area of most controversy. The guidelines I think give a lot of um sort of vague statements because there is a lot of um are equal poise in terms of the data but I'll go through them and then we'll discuss some some data quickly. So in terms of primary prevention and the A. D. A. Guidelines Um aspirin can be considered if someone's over 50 and has an additional risk factor. Um that includes family history hypertension hypercholesterolemia smoking or ckd and they cannot be at increased bleeding risk. Both guidelines if anyone's at increased bleeding risk. Aspirin is not recommended. And both guidelines if anyone over the age of 70 aspirin is not recommended. And that's based on the spree trial which came out in 2018 which was a large primary prevention trial that randomized elderly patients to aspirin versus placebo and showed no benefit um to aspirin in that population. Um And actually exposes them obviously to increase bleeding risk. So um and then um the A. C. C. H. A. Guidelines are similar um There's an error on the slide. It should be the age of the use the age of 40 to 70. Um For when aspirin can be considered. But there's no clear guidance really on who should be on aspirin. It's sort of an individual patient decision which is why coronary artery calcium I think has emerged as a potential tool as well. There's um several studies now showing that if patients have a coronary artery calcium score over 100 that they appear to derive benefit from aspirin greater than the risk of bleeding. So that's a tool that can be used when there is some diagnostic uncertainty Historically. Um aspirin has been recommended and it's I think progressively getting assigned a lower priority now in in guidelines. Um this was a meta analysis in 2009 from the anti robotic trialist collaboration Where they showed that in a with a composite endpoint of any serious vascular event. Again in primary prevention there's a 12% reduction in events with aspirin. However, when you look at how they break it down with the endpoints. When you look at secondary prevention versus primary prevention, for example, major coronary event. Secondary prevention, you get a 1% per year risk reduction, which is pretty significant in terms of absolute risk reduction over time for primary prevention, it's a point oh 6% risk reduction per year. So it's really a marginal benefit. Um and uh to contrast that you expose patients to significant bleeding risk, hemorrhagic stroke, extra cranial bleed risk are are significantly elevated. And to put this into context, some of the studies in this trial in this meta analysis go back to the 80s before there was widespread statin use before sort of modern blood pressure therapies and therapies for other risk factors. And this trial did not This man analysis did not include a lot of patients with diabetics and the small subset of patients that were diabetics, there was no benefit. But again, it's a very small number of patients. In 2016, the us preventive services task force did essentially did a simulation where they looked at different risk cutoffs and how many events were prevented and how much bleeding was caused. And based on all this, they found the greatest net benefit to aspirin in patients were 50-69 with over 10 10 year risk. Um and so they gave a recommendation to initiate aspirin in that group and then for the age group of 60-69, they said it's a reasonable thing to do but can be individualized and we'll come back to the U. S. P. S. T. F. In a second. Then there are three primary prevention trials in the in 2018 of aspirin. Um and one of them I alluded to, which was the spree trial and elderly patients, which showed no benefit. There was also the arrived trial which recruited patients at moderate vascular risk 10ure risk again showed no benefit. The only one that showed some benefit was the ascent trial which recruited diabetics. It showed a 12% risk reduction in their primary composite endpoint of cardiovascular events over a follow up of over seven years. Um One of the key things to note though is that the events in this trial were fairly low and they actually had to add T. I. A. As part of their composite endpoint to get enough events to for to have enough power in this trial. So if you look at their primary endpoint without T. I. A. Which I think is a more subjective, softer endpoint. Um there was not a statistically significant benefit and when they add to it does, you know, get that p value below .05. But again, this is balanced by a 29% increased risk in major bleeding. And the authors even conclude from that trial that it appears that the net benefit of aspirin isn't there for diabetics and to quickly finish here. This was a meta analysis of all the trials, basically up to 2019 including those primary prevention trials. Again in a composite outcome showed a marginal benefit of 11% risk reduction offset by 43% increase in bleeding risk. And when they look specifically at diabetes, they again see a similar thing. A marginal benefit of 10% relative risk reduction in a composite cardiovascular outcome offset by a 29% risk, have an increased risk of bleeding. And just now, last week the U. S. P. S. T. F. Released their draft recommendations for an updated guidance on aspirin and it looks like they're significantly downgrading their recommendation for aspirin across the board basically above age 60. They're not recommending it And in the age group of patients were 40-59, it basically gives a weak recommendation to individualize to patients but suggests that in general there's not going to be a net benefit to aspirin. And I think a lot of this change has been uh the improvement in other therapies over time such as statins, antihypertensive control of diabetes uh to the point where aspirin is no longer a benefit to a lot of patients. So I just want to quickly summarize talked about a lot of things but I think it can be boiled down to a few key points in terms of secondary prevention. People have had a clinical SCV event in the past and our diabetic high intensity statin is recommended I think for most patients who are diabetic you aim for an SDL less than 70 and the cardiovascular islands are a little more aggressive about that. And then combination therapy adding on a set of my burrow PCSK nine inhibitor can be used to reach that goal and low dose aspirin should be given for all these patients. It's important that as this USPS TF recommendation comes out and it's covered in the lay media that patients with a S. C. V. D. Histories are not taken off aspirin. Um We are seeing patients who have had a bypass surgery in the past were asking whether they still need to be on aspirin and that's answers are clear. Yes. In terms of primary prevention, you all diabetics should be on moderate intensity statin. Most diabetics should be on a moderate intensity statin at baseline. Um and really look for a reason to start a high intensity stand and then aspirin, it centers on shared decision making an individualized to the patient. But really if they're over 70 there's no evidence for benefit and aspirin if they're high bleeding risk. Their benefit is knocking outweigh the risk. So there's really a much more narrow narrower group that may benefit from aspirin. And this is where cornering calcium scoring may come in to benefit. So going back to this patient that we started with again it's a diabetic over 11 years with multiple risk factors all deals. 1 10. And when you plug this patient into that risk calculator to get a 6.9% uh calculation for risk, which would actually be above the sort of general population, below the general population threshold for statin use however, because this patient is a diabetic and they have CKD and they've had diabetes type two for over 10 years, that puts them in sort of the higher risk category with risk enhancers. So they should be on a high intensity statin. And I would say that the evidence is pushing us more and more away from aspirin except in sort of specific situations where you think the patient might be at increased risk for other reasons not covered by all of this. So I just want to thank the conference for for having me thank you to dr Sinica's uh and I know I went over a little bit but answering the questions, That's fabulous Harpreet, thank you so much. Um This was really good. And so um so relevant in terms of the most recent recommendations around aspirin, I think especially even in the last few weeks of information that has uh that has come out. So and I think you touched on a couple of questions that we've had in our chat that came up a couple of times related to one coronary calcium scoring. And when would you use that? And I think you you touched on that really nicely here, people at risk, but we're not quite sure which way to go. Maybe use that as the determining factor. Is that correct patients? Yeah. Intermediate risk asymptomatic patients where you're not sure which way to go. Exactly. Yeah. You know, we had a couple of interesting questions around diet. You did mention the mediterranean and the dash diet, but someone asked, what about Tito you know, we know that is a very prevalent fat at this point in time and has had some interesting outcomes as well. So any just thoughts on that and how those affect lipids in, you know, which way should we go with this? Right? Yeah. I'm certainly not a diet expert. I think people want to qualified we're going to talk about diet. Um, but I think at least in terms of large scale um, trials and data, uh the highest level of evidence currently exists for the mediterranean diet and for the dash diet. Um, there isn't sort of that same level of evidence for for keto and mediterranean diet has been kind of the most durable in terms of sustained benefit shown kind of across the board and pretty much any outcome you look at. Great and I'm certainly one that promotes that diet and loves that one as well personally. Um, there was one other interesting question uh asking I've it says I've seen transient increases in changes in lipids with active weight loss, do you recommend waiting a certain amount of time months after weight loss before rechecking lipids? Yeah. I think it's an interesting question. I think if there's a sort of an unexpected change you know in lipids or something like that, it's certainly reasonable to recheck you know in something like three months, 3 to 6 months and then sort of reassess. Um And it depends sort of obviously on what degree of a lipid changes things we're talking about but um certainly whenever I think there's something that's unexpected and you're uncertain before making a clinical change or change to someone's medications, it's definitely reasonable to reassess after a few months in a lot of time. Yeah. Maybe just two last points. I know we're just a a few minutes over but um one was uh the PC. S. K nine inhibitor. Can you just clarify for us, would that be in addition to a statin? Is that what you said or would you substitute it if if someone is not really getting to that LDL target that we think is appropriate. Pcs can I never would be in addition to status. The exception would be someone who has documented intolerance to multiple statins and gets unacceptable side effects. Then you could potentially substitute a PCSK nine inhibitor or keep them on sort of the lowest or the highest standard they tolerate but in general absent of side effects from sentence, they should be on PCSK nine inhibitors in addition to stands great. And then um the other thing that you mentioned, which again I get a lot of patients ask me about in the reduce it trial and you you spoke about um the use of Ecos append ethel and that in the control group maybe that had an effect, you know, you would limit it to just that one trial, don't generalize at this point, we really need a little more evidence. Can you just mention what the issues were with the control group? Just so that everyone in our audience understands this as well. Sure. So I believe in the placebo group, what they used was I think a mineral oil preparation um and in the placebo group they saw that their triglyceride levels increased um and follow up compared to baseline. And so and and they evaporate trial, their coronary artery plaque progressed and so I think that there's concern that the comparator that was used was actually increasing their risk potentially. And so it made a cost of an apple look better. The other issue that people raises that other omega three trials haven't panned out the same way that reduce it and evaporated. But the investigators, I think would point out to the fact that there is a whole wide range of mechanisms in different omega three fatty acids and they think apple is the one that has sort of a proven mechanism to work. So I think I think it probably is a benefit, but I think that it would be nice to see a cleaner trial with it may be a better placebo group to to really feel comfortable that that's a proven benefit. Yeah. I think the international looked at guidelines in the A. D. A. And stuff are starting to adopt it. So it is rising to the level of guidelines. Yeah. Good point. Maybe one last question. Sorry. Anything related to LP Little A. That you would recommend should we be trying to do anything more about this? I know you didn't touch on that. We didn't ask you to do it in this talk but just you know it's in the um area now of being tested to see if lowering that with a more specific agent might have an effect on cardiovascular disease. So we certainly need to wait for that. But any other recommendations. Yeah. So I personally believe that given that aspirin works in secondary prevention for S. C. V. D. It's likely that it will be of benefit to some group in primary prevention. It's just that that group has to be high enough risk to sort of be equivalent to a secondary prevention population. And we just haven't found that in trials in the primary prevention trials in 2018 part of the issue was some of them were underpowered and they also recruited patients who ended up being lower risk than they expected. Um But LP Little A represents a group of patients that are going to be at elevated cardiovascular risk without other therapies yet specifically targeted for LP Little A. So modifying other risk factors is important. Um there's very limited data on this and that's part of our area of research. But there was a study from the women's health study in in 2009, I believe, where they looked at people who had elevated LP little a levels and they benefited significantly from aspirin. Um So I think aspirin is certainly a reasonable consideration and I think coronary calcium scoring can help to kind of seal the deal in that patient population. Um but I think it's a high risk group without a lot of other options yet to offer them. So it may be something that is beneficial to those patients. Got it. Thank you so much. Are pretty was a pleasure to have you. Um really appreciate your time with us. Thank you so much. Thanks for having me
