Join Habib Samady, MD and Nehal N. Mehta, MD as they discuss further the Cardiovascular Grand Rounds presentation given by Dr. Mehta at Georgia Heart Institute on the relationship between diseases that cause inflammation and the effects on the heart that can follow.
Good morning. Welcome to our pearls and discussions after cardiovascular grand rounds on March 2nd. Our speaker this morning as you'll see is Dr Nihal Mehta um from the N. H. L. B. I. And I did do more formal introductions a little earlier. But now I just gave a spectacular talk on cardiovascular risk stratification really giving us unique insights and using biology imaging and really using psoriatic disease as a as a marker if you will as a as a model to understand a true sclerosis. Really, really cool stuff. So Nihal um absolutely incredible talk. So, tell me a little bit about, you know why use psoriasis as a model for a trio sclerosis. You know, I think the first and most important piece is whenever you're studying a disease state that you are interested in cardiovascular disease, you want to see that that disease state actually has more cardiovascular disease. So in 2006 we discovered that psoriasis accelerates the first risk for heart attack by about 55%. So we started with a common disease that we knew has inflammation because we can see the inflammation on the skin and it had this up regulated amount of prevalent heart attack and stroke. And so, um, I mean the journey that you just described to us and I know you hit the highlights because you wanted to focus on aspects of cardiovascular diseases. Unbelievable just unraveling the path of physiology of psoriasis as it informs the plaque and plaque progression. You talked about the shift and the and the cholesterol molecules to the right. Tell us a little bit about the two key two or three key aspects of story attic phenotype ng that reflects that higher prevalence and higher incident risk of cardiovascular disease. The talk focused on really three key elements Doctor Samadi and I think that the first one is systemic inflammation. It's long been known that those who have a latent amount of heightened systemic inflammation, whether it be periodontal disease, bowel disease, joint disease, that there's a heightened risk for developing cardio metabolic disorders. So that's first, systemic inflammation is rampant. The second piece is that we believe that the systemic inflammation is tied very closely together to retarding the function of HDL. So we see this constipation of cholesterol within the system and that Disl epidemiology as we describe it is driving all of the diseases that we are seeing as comorbidities and psoriasis. And then third besides the systemic inflammation and Disl epidemiology, there's this predisposition to obesity but it's not just generalized obesity, it's that visceral at a paucity. So our recent paper and J. C. I incite showed that when you're inflamed over time without it being treated, you expand out your visceral at capacity component. So I think it's three things that systemic inflammation. It's this idea of this metabolic disturbance of HDL dysfunction and this obesity and what those are all doing is they're allowing this non calcified plaque to start very early in life because of the endothelial cell inflammation, incredible. Yeah. So you it's interesting you you distill the Disl epidemiology as and you call it essentially HDL apathy right? There is an issue with HDL with the scavenging and removal of cholesterol um from the body through the liver. Um Do you feel that at least in psoriasis the primary pathology with respect to the Disl epidemiology resides in the HDL component, not the increased generation of the high the low density density. So I think doctor I think it's a combination of both. I do think that there's this when you have systemic inflammation, the liver itself responds and is a little bit curious. The liver first says, wait is the inflammation because I'm infected? And do I need to then dump out more sugar? So I'll become insulin resistant. Is the liver also seeing that I don't need to make good things like a po A. So I'm going to just stop making a pO a and save it for things like adrenaline and other proteins that need, you know uh you know, building so that shift from one to the other. Um I think allows us to know that the a po a reduction and do they make more LDL we haven't seen that in most of our chronic inflammatory populations. We see this increase in triglyceride e mia this mildly increased LDL but this very suppressed HDL. So I'm change that paradigm and saying, look it's not just that there's too much LDL that's being either made or consumed. But it's also that it's not being removed and focusing on both sides of it has actually shown some very promising four year data. Yeah, fascinating. And really, really well illustrated for us. Um So when you think about the journey as far as lipid therapies that we've taken over the years, um there was a whole push about almost a decade ago on focusing on raising HDL. Um and and as I as we learn more from people like yourself and others, we understand that maybe even going upstream from that in the case of psoriasis particularly, but ultimately potentially an overall atherosclerosis and targeting inflammation itself with some of the biologics or other sort of um easier to tolerated anti inflammatory drugs is the way to go. I mean, as as you've discussed, statins are here to stay HDL therapy specific HDL therapies have had their moments in the limelight if you will. And now as I understand it, you think we're really moving towards the field of anti inflammatory therapy for atherosclerosis. We are we are and I think that the most important part of our talk that I I found demonstrated that the audience realize that we're at 1/6 risk factor type of an approach where we can keep treating the statins or to keep using the statins and keep treating the lipids but there's clearly a residual risk that we are missing and it's probably a combination of metabolic inflammatory risk. Um So I do think that we need to remember that it's not just the A. P. O. B. A. Po a shift. It's not just this idea of treating this this primary source but knowing that treating inflammation may impact other comorbidities is important as well that diabetes risks goes down. And so I think we're at a point where we need to make this a cornerstone of our therapy and we're getting there. I want people to know that it took you know if you think of the first four s study or watch cops were talking you know we're all accepting the statin truth but it took 40 50 years to get us there. So I think it will take time just real quick in terms of the HDL raising therapies, they did it wrong. Um They were looking at HDL levels to say whether or not the HDL therapies are working and that was a complete error on the part of the people designing those studies. In fact when you look back at the aim high study and you look at those on niacin that reduce excuse me, that improved their HDL cholesterol reflux. They actually did see a benefit for events in that study. So you need to actually get your HDL more functional. Not just get more of it. In fact some people make a lot of non functional HDL so it looks great but in reality doesn't work. So I think that the HDL raising field took a hit but it still doesn't mean that I don't think that there's something very important about knowing that HDL works. Got it. Okay, so in the last few minutes let's kind of pivot and focus on coronary phenotype ng. Um we understand based on your talk some of the biology, some of the complexity of the vascular pathways and the biological pathways. It's almost akin to understanding heart failure therapies. Right? We started out with the angiotensin Renan angiotensin system and the and energetic and all these other pathways. So you know, biology is complex and you're helping us understand atherosclerosis. Um So let's think about practical management of patients with you know um secondary prevention, known coronary disease. Um let me give you, you know, just throw out an example. So you do have a 44 year old lady, you presented one in your talk. But let's say that doesn't have psoriatic arthritis but it does have the phenotype of the metabolic syndrome. Um and maybe had some shortness of breath on exertion. The B. M. I. Is high. Um there's a family history um and um they have hypertension, central obesity, all the phenotype we know as a clinician after taking the history, walk us through how you think about those patients. Do you use the Framingham risk score? Do you use imaging to stratify that patient. How do you take that on? That's a great question and I will walk you through step by step what we do because what I've learned over now 10 years of therapy of clinic therapies with these people and these patients is that the first thing that I do is I will start with defining why they have systemic inflammation. So I'll look at their psoriasis and I'll say, how much psoriasis do you have? How long have you had it? And where does it come? And how bad does it? I'm what about if the patient doesn't? Oh we're talking about a non story attic. I'm so sorry. So if the patient does not have story attic diseases, it's a simple history. Physical. And then depending on it, I know you asked about a risk score. I will calculate the A. C c H. A lifetime risk score. But I also use small uh you know sort of subtle indicators of higher risk features which are like I pointed out in a case family history of heart disease, family history of diabetes, family history of any stroke. So people are poo pooing the fact that these all you know sort of have a common lineage to them. So I'll definitely start with a standard A CCH algorithm and then I will move into a a screening ct or screening imaging exam. Um I will move usually to a coronary CAC score. So I'll get a an Augustine CAC score and I will take that Augustine CAC score. And if it's zero actually will tell the patient you don't have any evidence of advanced atherosclerosis. And if you feel like this is enough information for you and for me which I feel it's okay, I would leave them be and not start any other further therapy. I also would offer the patient if they had a different disease, let's say an inflammatory disease or something else, I would offer them a coronary cT A. And the reason is is that there's about and I put this in one of the questions before. There's about a 15% risk of having lumen ah graffiti defects um despite having a normal calcium score. So I do believe very strongly in image guided therapy and image guided decision making. Um And so that piece of the image guided um really is very new. Um in the last maybe eight or nine years people have said that if you're going to start you know therapy maybe you should know what you're dealing with. And then the final pieces I have very close follow up with dietician and exercise lifestyle folks. So I do believe in wellness. Um you know, work out of the massachusetts General Hospital recently um showed causality between stress and cardiovascular events um through the amygdala hyper activation. I didn't get a chance to go over that with you. But I would also focus on wellness and making sure that the patient has an idea of how to reduce these risks. But really it comes down to H. And P. Labs C. C. T. A. And then my plan includes wellness as well as um you know sort of diffuse preventive cardiology strategies. Fantastic. Well now I'm gonna ask you one last question and that is Fast forward to 2032. Okay. Um so because you're helping lead some of the research some of the imaging, some of the phenotype ng some of the Biomarker analysis. Also there's a lot of work being done with precision medicine and genomics. Right? And the question is is even though um You know the the snips and the other existing genotype analyses probably aren't ready for prime time. I want you to fast forward for our audience to 2032. And someone that same patient, middle aged metabolic syndrome phenotype presents to you um in addition to what you described today, what sort of imaging uh do you do plaque phenotype ng do you do flow analysis? What sort of you know bionic testing would we be doing would be doing? Would we be doing whole genome sequencing for patients at that point would be doing would we be doing specific um metabolic or inflammatory biomarker testing? Where would we be then? 10 years from now the patients will all walk in get a single drop of blood. They will have an inflammatory lipid and metabolic panel run which we do on all our patients anyway. Already that will include a glucose. It will include a. Glick a it will include maybe a crp if it's still accurate in uh in sort of um sensitivity dynamic range markers for inflamed populations. And I think the patient will get some sort of a whole body imaging test where they will be able to very quickly identify sources of high immune activity. So not a pet ct but something similar. Could be a whole body scan. Looking for uptake. Why am I saying a whole body. So we're also finding a beat that bone marrow proliferation and uptake are related to a progression of atherosclerosis and that's related to stress. So your body thinks stress it goes to the bone marrow dumps out immune cells. So if you have a whole body image that allows us to get all of these pathways at once it'll be 2032 single drop of blood whole body image. And the best part is the patient will leave with a therapy that impacts inflammation as well as metabolic dysfunction and Disl epidemiology. And I'm thinking that every patient will likely be on some sort of an S. G. L. T. Two inhibitor. Um I do that believe that some most people will be on some sort of culture scene or some sort of an anti inflammatory maybe turmeric if you believe in you know alternative therapies. Um And then I think that blood pressure will be taken seriously right now we don't spend enough time taking blood pressure seriously. Um So I do think that in 2032 we'll have guidelines that say your LDL should be in your seventies, your whole life, your blood pressure should be in the one twenties your whole life. And I believe that you're going to need some addressing of your inflammatory metabolic dysfunction. We all get it all. Humans by the age of 80 will have inflammatory metabolic dysfunction, they call it inflammation. But we just need to short circuit it. Wonderful. Well listen, that that was absolutely outstanding. Um I want to thank you so much for enlightening us here to Georgia Heart institute. And I look forward to our ongoing collaborations and getting you down here in person to Gainesville Georgia. So thanks again for your time and we really enjoyed it.
