The Cardiometabolic Approach: A Solution to Modern Disease Risk Assessment

The Cardiometabolic Approach: A Solution to Modern Disease Risk Assessment 

[00:00:00] Welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine, and wellness medicine. 

[00:00:18] As many as 45% of Americans have a chronic disease like diabetes, nonalcoholic, fatty liver disease, chronic kidney disease, cardiovascular disease, and even common endocrine disorders.

[00:00:31] And these diseases share common risk factors, making it essential to shift from treating them in isolation to adopting a more integrated, complimentary approach.

[00:00:39] I'm Dr. Mason Lasko, a researcher by training with a passion for learning. And I'm here today to discuss our cardiometabolic approach as a way to define the intersection of chronic disease. Walking us through this approach today is Dr.

[00:00:53] Mark Penn founder and chief medical officer

[00:00:56] for Cleveland heart lab at quest cardio-metabolic center of excellence in [00:01:00] Cleveland, Ohio. Dr. Penn is also a board certified cardiologist and director of research at Suma cardiovascular Institute. Welcome Dr. Penn, thank you for joining me today.

[00:01:10] Thanks, Mason. Great to be here.

[00:01:13] From your perspective, Dr. Penn, why is there a need for a cardio-metabolic approach?  

[00:01:19] Well, the biggest need for a cardiometabolic approach or the reason for it is the risk factors that drive heart disease.

[00:01:24] Still the number one killer in America and the Western world have changed. We talk about You know, meat and potatoes in the 70s and 80s is a driver of cholesterol that then led to heart attacks. We forget that those meat and potatoes were followed by a cigarette. We now exist in a time where we have the lowest smoking rate in the history of our country.

[00:01:47] Yet since 2010, the risk of heart attack and stroke are actually increasing. So how could that be? And the reality is, in 1994, when the 4S trial came out, the Civistat survival [00:02:00] study, um, There was a call for low fat diets because clearly statin therapy saved lives. The problem is a low fat diet is really code for high sugar.

[00:02:12] Um, so we're now about a generation to almost 2 generations into a increased sugar diet in our country. We've become heavier, we've become sweeter, higher sugars, and those risk factors are now driving heart disease, even though our LDLs are far lower than they were in the 90s, and even though we're smoking far less than we did.

[00:02:35] And the challenge becomes these risk factors are now multifactorial, and In a given patient, their risk profile has to be individualized.

[00:02:46] And... , I think the most important thing to do is de silo the thinking,

[00:02:51] Right. So if you have cardiometabolic disease, high sugars, you're overweight, you have inflammation, your blood pressure's up, the reality is you're at [00:03:00] risk of kidney disease, liver disease and heart disease.

[00:03:05] So. we need to understand it's, it's not thinking about the kidney, thinking about the liver, thinking about the heart at different times. It's thinking about the disease profile that drives a commonality of the diseases across the organs.  

[00:03:19] Yeah, and I love the way you put that, you know, it's really a disease profile that encompasses your risk for cardiovascular. metabolic.

[00:03:28] Liver kidney and endocrine disease.

[00:03:31] You mentioned prevention, which I know is a critical focus for the cardio-metabolic approach. can you talk from your perspective about how the cardio-metabolic approach has really put prevention in the forefront of provider's minds?

[00:03:45] Yeah, so the work we've done, and then hopefully we'll soon publish, uh, recognize that a lot of patients have a condition for years before they have a disease.

[00:03:56] And if we use cardiometabolic testing to define who has a [00:04:00] condition, the reality is the likelihood of diet and exercise to reverse that condition so they never develop a disease is very possible, We send people home every day with 5, 4, 5, 5, you know, Dr. Valentin Fuster's study, um, has shown that those folks with 5 likely have atherosclerosis in multiple clinical beds.

[00:04:27] Yet, we're telling the patients they're normal. It's not normal.

[00:04:30] We need to recognize that the A1C is a general measure of the patient's blood sugar over the last 90 days. And they may have a very high insulin level to maintain an A1c, say, of 4.

[00:04:49] As their pancreas loses the ability to make insulin, the beta cell dysfunction, their A1c will climb. Not because they're [00:05:00] any different than they were, It's that their pancreas can no longer support that blood sugar. To get insight into that early in the disease,

[00:05:08] We can actually turn the whole ship around and prevent progression. Um, the insulin resistance score turns out to be incredibly powerful because we can identify who amongst those normal range of A1Cs actually is at higher risk. And whether that higher risk is educating the patient, young lady, young man, you may have normal a1c, but the reality is you're developing cardiometabolic disease.

[00:05:37] You need to diet and exercise and reverse this condition. So you never get a disease we need to recognize there are people who have conditions, they're early in their disease journey, and we can truly prevent the disease, not just the consequence of the disease. a lot, of the focus seems to be if you're diabetic, let's prevent heart disease.[00:06:00]

[00:06:00] Let's prevent the diabetes, right? Yeah, that works much better.

[00:06:05] Exactly. So prevention is key and thus identifying where your patient is along a spectrum of metabolic risk. Using tools like an insulin resistance panel with score can identify insulin resistance and help improve patient care. And I think that that resonates with providers.

[00:06:21] So with the understanding that insulin resistance and metabolic dysfunction can contribute to more than just cardiovascular and metabolic disease states, . But also chronic kidney disease and fatty liver disease.

[00:06:33] And integrated into the approach is endocrine disorders.So how do endocrine disorders play a role in the cardio-metabolic disease spectrum?

[00:06:44]

[00:06:45] so it's not all endocrine diseases to be clear, but you're exactly right. There are some that absolutely play a role here, right? Patients who are hypothyroid cannot exercise. They're going to put on weight.

[00:06:54] They're only going to worsen their cardiometabolic disease. [00:07:00] Aldosteronism is recognized more and more as a driver of hypertension in our patients and you can put them on all kinds of drugs, but if you don't recognize that they have hyperaldo, and you're not treating them with spironolactone or something to address that, the reality is you're not going to get their blood pressure under control.

[00:07:18] Um, low T, uh, low testosterone men, uh, erectile dysfunction, they also are going to not be able to build muscle. They're going to have more fat. They're going to be at higher risk of metabolic disease. Women with PCOS, polycystic ovary syndrome, clearly are at risk, increased risk of heart disease. And that is because they're metabolically deranged.

[00:07:44] So we need to think about how. obesity and, cardiometabolic disease worsen our endocrine system, but we also have to recognize how our endocrine system contributes to cardiometabolic disease. It's definitely a two way [00:08:00] street. 

[00:08:00] Yeah. And we see it pretty often , right ? Where. A person that has elevated lipid particle count compared to where they should, based on they're a little bit panel. And turns out really what's driving. That is hypothyroidism, for example. So assessing cardio-metabolic conditions in conjunction with an alongside endocrine disorders is really crucial.

[00:08:20] Now with the backdrop of identifying metabolic risk as drivers in chronic kidney disease, fatty liver disease, even endocrine disorders, cardiovascular disease.

[00:08:32] It's necessary then to start to discuss how we actually assess and manage individuals who have these chronic conditions who have already passed that threshold.

[00:08:41] What would you do if a patient came into your office, how would you assess them more holistically for cardio-metabolic conditions?

[00:08:48] So the approach is to find their cardio metabolic risk, which is the shared risk to your point. Inflammation, blood sugar, things of that nature, the endocrine testing, if that's [00:09:00] in play, then we look at the, the heart, the kidneys and the liver.

[00:09:05] We want to start with the liver. I think, you know, Fatty liver is far more prevalent than we realize. The best way to actually decrease fatty liver is to lose weight. If you can lose 10 percent of your body mass, you will significantly impact the fat in your liver. If you look at GLP one literature, they may slow heart disease. They may slow renal disease, but they actually reverse fatty liver disease. So that's critically important. In addition, we need to look at AST and ALTs to see if there's any evidence of liver damage, transaminitis, um, far too many people, claim that that's because of statin therapy and that they, they inappropriately stop statin therapy.

[00:09:47] And the reality is they have,non alcoholic, or metabolic associated liver disease.and to further characterize the liver in that setting, you need to measure a fib 4, which takes into account the AST, the [00:10:00] ALT, platelet count, and the patient's age. If that's elevated, then, you know, they have some evidence of fibrosis, which is concerning, and then you follow up with an ALF, uh, Enhanced Liver Fibrosis test.

[00:10:12] the Elf test then will give you a sense of the likelihood of your patient having a liver related event in their lifetime. Um, and all these markers can be reversed over time. And if you have an elevated Elf. High risk alifier, I think you'd need to send somebody to a hepatologist

[00:10:29] but if you're low risk or or mildly elevated risk as a primary care provider, you can manage these patients again, mostly by weight loss, certainly not stopping the stat and keeping lipid therapy in place. And from there, then, you can deal with your hyperglycemia, your hyperinsulinemia, which is hiding, or at least they're driving part of that.

[00:10:53] So that's for liver. For renal disease, it is critically important that physicians more [00:11:00] commonly measure albumin carotene ratio in the urine along with the carotene. We all need to remember that stage 1 CKD is a normal GFR with an elevated protein area. You cannot diagnose CKD stage 1 without checking for protein in the urine.

[00:11:19] But far too often, we're comforted by the fact that the GFR is normal and we don't look any further. Then if you look at CKD two, stage two, stage three, if you are gonna determine whether you've sufficiently treated that patient to prevent progression of the renal disease, you need to look at the albumin creatinine ratio in the urine.

[00:11:40] If it's low, less than 30 micrograms per milligram creatinine, they're not likely to progress their disease. But if it is still elevated between greater than a hundred or greater than 300, the reality is there are significant risk. of progressing the renal disease and more treatment needs to be done. And there are [00:12:00] more and more drugs coming out to try and protect the kidneys, in this setting.

[00:12:05] And we, we really need to use that. Um, so that's the focus on renal disease in addition to patient education, low protein diets, hydration, all those things that they can do to also further. Reduce their renal progression and of course, blood pressure control. And then for the heart, it's really looking at their lipids.

[00:12:29] It's looking at, you know, hyper triglycerideemia. when you have elevated triglycerides, you have elevated remnant particles. Those elevated remnant particles are absolutely pro inflammatory. And in those patients who have elevated markers of vascular inflammation, like myeloperoxidase or LP PLA2 activity, or even Relatively nonspecific, but HSCRP, uh, we know those folks have, you know, active disease, and that's a problem.

[00:12:55] Similarly, you need to measure an ApoB, because if the ApoB is elevated, but the [00:13:00] LDL is controlled, that implies there's a little bit of LDL, but a whole lot of, LDL particles. Those are small, dense LDL particles, and those are, like the remnant particles, pro inflammatory and pro atherogenic. And we need to get the particle number down, and certainly those are the folks Who need their LDLs dropped to below 70, uh, and maybe lower, but those folks still have a lipid problem and need more aggressive therapy.

[00:13:27] So that's really the way we walk our way through the specific organ, but we start by defining what the cardiometabolic risk is. And again, that's an A1C and an insulin resistance score. Uh, and things of that nature

[00:13:42] I love the idea that we have laboratory tools to help empower both patients, to identify their risks earlier and empower primary care providers to really have the tools to assess risk in their patients much sooner.

[00:13:57] Because ultimately primary care providers [00:14:00] are really going to be the audience who can take this approach and integrate it into their practice.

[00:14:06] Yeah, so Importantly within the approach each and organ system The testing is designed to let the physician know when to refer to a specialist So in the case of liver disease if you have a high risk health patient should be referred to a hepatologist If you have somebody who you cannot get the protein area under control, their CKD is progressing, they should probably see a nephrologist, but the reality is the testing allows primary care, family medicine, internal medicine physicians to manage the patients on their own to get the feedback they need and to recognize when in the patient's journey, they should be referred to a specialist.

[00:14:51] And those who have a nephrologist. You know, lipids that, for lack of a better term, don't make sense, there are a lot of genetic, uh, [00:15:00] drivers of, of, uh, hyperlipidemia, you know, those are the folks who probably do need to go to see a lipidologist, but the reality is there's a lot of tools, uh, for the primary care physician to treat those lipids.

[00:15:14] And our feedback from our testing will help, physicians understand when they're having success, lowering inflammatory markers, lowering lipids, lowering APOB, lowering particle number, um, versus those who really just aren't responding as you anticipate and need to go to a specialist.

[00:15:34] Well, I think that it's very clear that you have a passion for addressing chronic illness from the perspective of the root cause and trying to identify where that patient's risk is much sooner so that we can prevent disease. And you know, you as a cardiologist, it's very powerful to hear that you're not just interested in assessing cardiovascular disease, but also other end stage disorders that are really [00:16:00] impacting our society like fatty liver and chronic kidney disease and endocrine. disorders. Uh, as well as metabolic and cardiovascular risk, what are some key takeaways from our conversation today?

[00:16:12] Yeah, I think key takeaways include, if you're going to live and die by the guidelines, you're practicing old medicine and, you know, we need to recognize that the forest trial, uh, some of that survival study.

[00:16:28] Had 4% diabetics. I doubt any of us remember the last time we saw 4% of our patients having diabetes. Hmm. It's just not relevant to how we practice today. We also have to recognize that the average LDL in that study was 188. 

[00:16:46] If you look at more contemporary studies, like the Improve-IT trial, um, where everybody had a heart attack within 10 days of enrollment. Only a third were on statin at the time they had their heart attack and only [00:17:00] 45 percent were on aspirin.

[00:17:02] So the idea that we're really good at identifying patients at risk is just not true. The literature and the data don't support it. So unless we're going to get more proactive in assessing risk and assessing who's developing risk. We're still going to have 45 percent of people die at home with their first heart attack.

[00:17:24] It's just not going to change. And we can debate this drug versus that drug, right? I mean, GLP ones in the select trial, lowered MI and mortality rates by an absolute reduction of one and a half percent. Relative to the 45 percent of people who die at home or the first heart attack. That's really not much.

[00:17:47] So. We need to think differently, and we need to recognize that the disease drivers have changed and that disease drivers now aren't just driving heart disease. They're driving [00:18:00] kidney disease, liver disease, and quite frankly, dementia, even though we don't talk a lot about it. So we need to just think differently I've said this for two decades, and it's truer now than when I first started saying primary care. Physicians are the ones who determine how many heart attacks their patients have. Cardiologists stop them. We now, in fact, have further empowered primary care because the drivers of the disease are exactly what you're seeing every day when the patients walk through the door or whatever age they are.

[00:18:34] Whatever weight they've become, whatever lifestyle they've chosen, family history is not changed. And, you know, whatever sexual history or reproductive history they have, meaning men who have erectile dysfunction and women who have gestational diabetes or hypertension of pregnancy or preeclampsia, those folks all have significantly higher risk of heart disease.

[00:18:59] So it's [00:19:00] primary care that really can help educate, define early risk. And diet and exercise early drug therapy later, but really have a significant impact to make people healthier. Um, and, you know, our testing is, I think, evolving in a way where, yes, your A1C is normal, but we can tell you who in a normal A1C still has high risk.

[00:19:24] Um, and then we can, we can go from there, but the earlier we can define this risk, the more likely. We'll be able to prevent disease, and we got to stop thinking about heart attack, stroke, renal failure and liver transplant is the disease. The disease is cardiometabolic disease, and we need to turn that around as early as we can because all those other organs.

[00:19:48] We'll get better or be prevented from ever having disease. If we do that.    

[00:19:53] So powerful. Thanks so much for your perspective. And thanks for being here, Dr. Penn, it's always a pleasure.

[00:19:59] great, [00:20:00]  

[00:20:01] that's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app, and be sure to check out Quest Diagnostics Clinical Education Center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world, one life at a time.