Welcome to Module 6. Today, we're going to talk about cardiometabolic disease and my goal is to really bring everything together with all of the other modules and how this comes together in a constellation of symptoms, pathology, as well as disease management. Cardiometabolic disease is known by several different names. We describe it now in 2023 as a disease, but historically, it's been described as a syndrome. Many, maybe probably a decade or more ago, it was described as Syndrome X for a while and by metabolic syndrome. I've heard it as insulin-resistant syndrome, as well as plurimetabolic syndrome. But the concept that it's this constellation of etiologically linked cardiometabolic risk factors that include dyslipidemia, hypertension, and high fasting plasma glucose, or as we're going to learn more about, which is really underlying insulin resistance. It's a metabolic syndrome. I mean, it is a syndrome. It's a conglomeration, again, of all of those things. But it provokes or is provoked by, it's a little bit of a cyclical effect we'll talk about by weight gain, particularly an increase in intra-abdominal fat accumulation, which is mirrored by a large waist circumference. When we get into the diagnosis, one of the things we're going to look at is waist circumference and start measuring that. Prevalence is expected to rise dramatically in parallel to the global obesity epidemic. I'm going to show that here in just a few minutes with some data. It's chronic and is progressive. Then finally, cardiometabolic disease doubles the risk of cardiovascular disease. But all components are reversible with an effective treatment approach, including weight management. We're going to talk a lot about that today. I think the key is, is it's reversible if we get in front of it in time. Prevalence-wise in 2023, we see this in males, 35.3 percent of men have what would be considered cardiometabolic disease, 33.3 percent of women. In the US, the highest prevalence is amongst black females at 40 percent. Components are influenced by both genetics and lifestyle, although no single gene or common genetic trait has been identified. Then early identification and lifestyle management are key to effective risk reduction. Again, we'll talk a lot about that. A few years ago, the cardiometabolic alliance came together and developed through a working group, a model for metabolic syndrome. I think this is really important and this will make more sense as we start to get into the different constellation. But they describe a stage A, where we have a risk scenario where patients are overweight. We start to see that ectopic or abdominal fat. There may be racial susceptibilities or higher risk ethnicities, poor physical activity, and maybe parents, older generation that has metabolic syndrome or metabolic disease. Stage B is where they're at risk and have greater than one of the criterion. Blood pressure, glucose, high triglycerides, low HDLs, or alternative risk factors. Stage C, they have three to five of the criteria, the waist circumference, the blood pressure, the glucose, and stage D, we actually start to see them with end organ damage that can include cardiovascular disease, straight, full-blown diabetes, chronic kidney disease, obstructive sleep apnea, non-alcoholic fatty liver disease, so NAFLD, or some others that we'll go over here in a little bit. But I think this is a really good framework to think about your patient populations and where they fall, and then how aggressive you need to be with their risk reduction. As far as diagnosis criteria, there's a number of organizations. This is like when we get into the diagnosis of hypertension or even diabetes, what the actual number is. In this case, it's a little bit different. I've provided two different organizations as far as their level of definitions, and there's actually more than that out there, but these are the two that are the most common. The first one was provided by the National Cholesterol Education Program, and it really, any three of these features, so waist circumference, rise in their triglycerides, reduced HDL, hypertension, or raised blood pressure, or raised fasting plasma glucose, and you can see the numbers there. The second organization that I pulled was the International Diabetes Federation, and you can see their numbers a little bit different. The waist circumference is a little bit smaller, and the fasting plasma glucose is a little less, so they are more aggressive, actually, with diagnosis and therefore management. So we're gonna walk through a number of these risk factors, being sedentary lifestyle, poor diet, obesity, dyslipidemia, hypertension, insulin resistance, and pro-inflammatory and thrombotic state. We'll start with the lifestyle factors, so weight gain, diet high in saturated fat, smoking, inactivity, and excess alcohol intake. All of these promote an increase in intra-abdominal fat and those metabolic risk factors. From an obesity perspective, couple things here. The US prevalence of obesity in 2018 was 42.4%, with 9.2%, just under 10%, being considered severe. That's expected to increase to 50% by 2030. 50% of the US adult population would be considered obese by 2030. In 20 years, one of four Americans was severe obesity. So again, right now it's one in 10, just under one in 10. In another 20 years, if we consider on the current trajectory, it's one out of four, severe obesity. We're one standard deviation increase, and a BMI increases the odds of coronary artery disease by 20% and type 2 diabetes by 67%. So this really is the crux of one of our mainstays in risk reduction, and that is weight management and weight loss. So what's kind of going on here? Well, there's a few things that are happening. One has to do with the fat distribution or the adipocyte distribution. If it's visceral, which is organ related, it's the fat that accumulates around our abdominal organ. So the intra-abdominal obesity, that is a different type of fat than what we would get in the peripheral areas. It also has to do with cell size. So fat cell size, adipocyte size, and then adipocyte function or dysfunction, where we get some hormonal responses related to that. It's also related to race, lifestyle behaviors, and some genetic factors. So we'll start describing or talking about dyslipidemia and what's really considered atherogenic dyslipidemia. So by definition, it's an elevation of the triglycerides at greater than 150 milligrams per deciliter or 1.7 millimoles per liter. We also see in combination a low concentration of HDLC. So less than 40 in men and less than 50 in women. The prevalence of lipid abnormalities is higher among individuals with diabetes contributing to their cardiovascular risks. So dyslipidemia is really important when it comes to the management of these patients. The next one is hypertension. So mentioned this already, typically what we would define hypertension as a greater than 130 systolic over 85 diastolic. So greater than 130 over 85. Interesting, excess weight accounts for 65 to 78% of the risk of essential hypertension. So higher weight increases your risk for developing hypertension. Only 43.5% of individuals who are prescribed antihypertensive agents had controlled hypertension. And often multiple antihypertensive drugs are required to control hypertension. So you will learn that, or you may have already learned that from the hypertension module. We don't do a good job of either diagnosing, managing or managing to goal patients with hypertension. The next one is insulin resistance. So insulin resistance plays a key role in metabolic disease pathogenesis and relation to cardiovascular risk. There's a few things here. So prediabetes is associated with a threefold higher prevalence of unrecognized myocardial infarction. And insulin resistance is associated with atherogenic dyslipidemia. So that elevated triglycerides and the low concentration of HDL that we just talked about is directly related to insulin resistance. Insulin resistance also is associated with an increase in prothrombotic and pro-inflammatory markers. So when you start to think about vascular disease, embolic disease, that goes along with all of this. We also see an increase in sympathetic tone and sodium retention, which may increase blood pressure. So if you recall from the hypertension module, we talked about the different drivers of hypertension, sympathetic tone, sodium retention, were two key areas or two key drivers. Those are a result of insulin resistance. We also see sleep disordered breathing, chronic kidney disease and then polycystic ovarian syndrome. So see how it's all tied together. Now, I think this one is really important and this is the next few slides kind of come together and you almost have to go through them in very quick progression to understand the impact. But what these are is a map of the U.S. that outline the age adjusted prevalence of diagnosed diabetes and obesity among adults by county in the U.S. starting in 2004. I'll let you read through the methods, but I want you to follow this progression. So this was in 2004. So diabetes and obesity, 2004. 2009, so the darker the colors get, the more prevalence or the higher number of patients we have. 2014, 2019. So I'm gonna quickly go back to 2004. The majority of the U.S. was still white or very light colors. 2019, the majority of the U.S. are dark colors or mid colors. So this just goes to show that climb of when we described the degree of obesity by 2030, we can see how that's happening and where that's happening across the U.S. I cannot lie, this sort of took my breath away when I saw it all lined up like this. So we have some work to do. And then the last piece I wanna walk through is the subclinical inflammation. And we here do see some inflammatory marker elevation. So C-reactive protein, uric acid, cytokines, and plasminogen activator inhibitor one all go on to create a prothrombotic state. So this really leads to that vascular disease, vascular dysfunction. All of it comes together related to the end organ damage. And I mentioned these earlier in the talk, but the first one is non-alcoholic fatty liver disease. So fatty liver disease with steatosis, fibrosis, and cirrhosis. These patients can go on to develop end-stage liver disease related to this. Heart failure. So the heart failure with reduced ejection fraction, and we also see heart failure with preserved ejection fraction. And we'll talk more about that, or we did talk more about that in the hypertension module. Renal disease, so chronic kidney disease. Couple things here. We can see a diabetic nephropathy, can also see a renal vascular disease related specifically to the vascular dysfunction we see at these patients. Atrial fibrillation driven by hypertension of obstructive sleep apnea, also increasing patient's risk for stroke. Full-blown diabetes type two, where the insulin resistance and the persistent hyperglycemia go on to develop both macro and microvascular damage. And then finally, dementia. So an increased risk of cognitive decline and vascular dementia is noted in these patients. So a few principles, and then we're gonna get into management. So the first one being that cardiometabolic disease is reversible. So it's reversible. If we can get in front of this and manage these risks or manage these different pathologies, we can minimize or even potentially inhibit end organ damage. Lifestyle behaviors, including nutrition and activity are significant risk factors and predictors of cardiometabolic disease. So when we get into therapy, activity and nutrition are gonna be key interventions. Prevalence is increasing as obesity increases and population ages. And I just showed that to you again, mind blowing. And then finally, although the definitions are a bit dynamic, the underlying etiology is the same. And I think the reality is any patient that has risk initially starting with some weight gain is really important that we get on the front end of that, educate and provide support around good weight management. So I broke therapy considerations into two sections. We're gonna initially start with disease prevention and then I'll talk about the actual disease management and really both of these kind of come together. So our therapy goal for our disease prevention is I mentioned already, weight management. So we wanna reduce excessive fat accumulation, we wanna improve glucose tolerance and we wanna improve lipid management. Our management goal for weight management focuses on lifestyle changes for patients that include nutrition, physical activity and in some cases, surgical weight management procedures. I mentioned these already, our cardiometabolic disease risk factors. I don't think we can talk about these too often but those that lead to obesity are the sedentary lifestyle and the poor diet. So from a sedentary lifestyle perspective, there's a few things again, just very logical but restricting television, computer use, thinking about our sedentary work life, our sedentary out of work life and what are some of the things that we can do to just keep moving. Avoid motor transport for short journeys, taking walks or bike rides and then activity oriented holidays and leisure time. So those are kind of high level broad recommendations. So what do we really recommend when it comes to physical activity? So aerobic exercise like brisk walking, swimming, cycling or jogging are advisable at greater than 150 minutes per week. So if you break that, divide that by seven, it's less than 30 minutes a day, five days a week is really the minimal recommendation. Highly intense exercises and supervised physical programs are recommended for controlled and supervised weight management or weight loss. Physical activity can be spread over three days a week with no more than two consecutive days without exercise or five days a week. And then use of smartphones, pedometers to support patient engagement. So there's a lot of literature and some good best practices related to engaging patients in physical activity. But as mentioned here, supervised programs are really, really helpful to create engagement and create accountability. All right, nutrition. So our overall goal with nutrition includes a few things. One, rate reduction to improve sensitivity to insulin, right? Our whole, one of our main goals is to decrease insulin resistance. Multiple diet approaches have been proven and recommended and I'm gonna go through a few of those. A referral to a registered dietitian for medical nutrition counseling can be incredibly effective and valuable. I think it's important to know keto diet, intermittent fasting. When you look at the recommendations and the guidelines around cardiometabolic disease management or treatment, those are not recommended. There's a lot in the literature, again, depending on your program and some of the different people that you work with, but the general guidelines are more of a well-rounded, well-balanced meal versus a keto or an intermittent fasting. So there's a couple of them I'm gonna lay out for you. The first one is the Mediterranean diet. The benefits of this diet include weight loss, lower blood pressure, improved lipid profiles, improved insulin resistance and lower levels of inflammation and endothelial dysfunction. The diet itself is a foundation of vegetables, fruits, herbs, nuts, beans, and whole grains. The meals are built around plant-based foods. They do have moderate amounts of dairy, poultry, eggs, and seafood and red meat is only an occasional component. So largely plant-based with a little bit of protein related to dairy, poultry, eggs, seafood, outside of your plant-based protein, like the nuts and the beans. So that's the Mediterranean diet. A similar diet is the DASH diet. So in this case, the benefits include improvements in triglycerides, diastolic blood pressure, and fasting glucose. DASH stands for Dietary Approaches to Stop Hypertension. So it's pretty logical. In this case, they're focused on both salt intake, sodium intake, and your dietary nutritional intake, but they're limiting the daily sodium intake to 2,400 milligrams with moderation of other food groups. So again, moderation. The diet is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish and nuts, low in sweets. So sugar, sweetened beverages, and red meat. It's rich in potassium, magnesium, and calcium, as well as protein and fiber. And the next one is the low-glycemic diet. So the benefits of this is that it may improve glycemia and dyslipidemia. Again, you're gonna see some underlying themes with these diets, but it's whole grains, fruits, and vegetables. It eliminates the high glycemic beverages, and it's low in glycemic index and glycemic load. And the last one is the high-fiber diet, which the benefits include weight loss, improved systolic and diastolic blood pressure. In this case, you're achieving or you're aiming to achieve greater than 30 grams of fiber a day. It's high in fruits, vegetables, whole grains, fiber, lean animal, and vegetable proteins. So reduction in sugar, sweetened beverages, and moderate to no alcohol intake for this diet. Again, as you see, the foundation of all of these diets are plant-based, so fruit, vegetables, whole grains, with some limit of animal-based protein outside of, in addition to your vegetables and your vegetable-based protein or plant-based proteins. Okay, so we talked about nutrition. We talked about exercise. Now let's talk about further weight loss outside of just exercise and nutrition. These are the primary management interventions. Obesity in and of itself is defined as a BMI greater than 21 to 22 kilograms per meter squared. Exercise and nutrition are the primary mainstay management interventions. Pharmacologic options are limited. However, we have some newer ones. So the Orlistat has been around a while. You can read about that. Not incredibly effective. The newer ones that we're seeing are the semaglutide and the lagleratide. And both of these are GLP-1 receptor agonists, and we're starting to see some really great outcomes with these. So I think more to come, but the studies are good, and they're good even when related to cardiovascular risk reduction. And then finally, surgical intervention, only for patients who have failed both exercise and nutrition, as well as pharmacologic, may then go on to benefit from a surgical procedure. But this is an area where, again, working very closely with a weight management bariatric program and really defining which patients and at what point in their management journey should they be referred, what that looks like for your program. The next one is tobacco abuse. Your outcome goal here is complete avoidance of smoking. Smoking cessation should be encouraged. Smokers do have an increased risk of diabetes-related microvascular and mastrovascular complications. Nicotine replacement therapy, as well as pharmacologic therapy, may be needed. So a few takeaways here. Initial treatment and prevention include both weight management through nutrition and exercise. Nutrition recommends typically include a diet of vegetables, fruits, low-fat dairy products, whole grains, poultry, fish, and nuts. Exercise should consist of 150 minutes per week, and smoking cessation is imperative. And now we'll move on to the pharmacologic therapies. So the first one being dyslipidemia. The goal here, and you're gonna get quite a bit more of this in the other modules because we have specific modules related to dyslipidemia and hyperlipidemia. So this is just an overview. Their overall goal is to increase HDL and decrease triglycerides. It does include LDL lowering benefits. So you'll get benefits on both sides of these. I did provide you the definitions of dyslipidemia and the overall goals of the reduction in triglycerides and the elevation in HDL. Pharmacologic therapy, statins. Most patients will qualify for a statin and or adding on options that include azetamide and PCSK9. Phenylfibrates may be used for elevated triglycerides, but again, we covered a lot of this in much more detail in the hyperlipidemia modules. I did provide, again, more for reference. So I will not read through all of these, but you have it for easy reference. Hypertension, our overall goal here is a systolic pressure less than 130 and a diastolic pressure of 80 or less. And again, pharmacologic therapy will includes an individualized approach based on comorbidities and risk factors and specifically type twos, or as an example, type two diabetes or diabetics benefit from ACE inhibitors or angiotensin receptor blockers. And for those with cardiovascular disease that's already been previously diagnosed, they benefit from ACE inhibitors, ARBs and maybe beta blockers. So you start to think about these patients and their additional comorbidities that really helps drive the pharmacologic plan or management for these patients. So again, just added a little bit in here for reference. I'm not gonna go through all of these. You will get them in much more detail in those other modules. The next area is insulin resistance. As I mentioned, weight loss and lifestyle management are key for this one. For diabetes prevention, a greater than 16% risk reduction per kilogram of weight loss is what we see. And then weight loss of greater than or equal to 5% is needed to produce beneficial outcomes in glycemic control. But you figure 5% in a 200 pound patient is 10 pounds. 5% in a 300 pound patient is 15 pounds. So it's not a huge amount of initial weight loss that's required to start to see some benefit. The flip side also means it doesn't take a lot of weight gain to start to see some detriment. So again, this is really important to manage early in the disease process. For those with prediabetes, a six month intensive lifestyle modification is typically the first line therapy with exercise, nutrition, and weight loss. If you have issued, they do not reach their goal or you still have concerns or evidence of insulin resistance, then we move into the pharmacologic management. Again, you'll get this in much more detail in the diabetes modules, but the overall goal is improve glucose tolerance, improve lipid profile. And you can see here how both these agents do provide those benefits. And I've kind of walked you through several of the initial therapy. And again, you'll get this in much more detail in your diabetes modules. So final takeaways as far as this area, multi-risk factor management is key. So again, if you think about the definition, most of these patients are gonna have at least two, likely three of these different risks and comorbidities. So hypertension, hyperlipidemia, insulin resistance, that oftentimes all of them are related to a foundational elements of obesity or weight gain, sedentary lifestyle, that kind of thing. Pharmacologic management should take into consideration comorbidities and other risk factors, and then care coordination and education will improve adherence and patient engagement. And then finally, just kind of wanna pull it all together is related to cardiometabolic disease management. An evidence-based cost-effective programmatic approach is really important in these patients. You know, if you take a patient and you only manage the hypertension, but we don't manage the other areas or somebody else is trying to manage and we're not coordinating, you can understand how things just, we just don't do a very good job of it. So one of the things that we're starting to see and really advocate for are cardiometabolic disease management programs, or at least care pathways that include assessing and managing all of the different components. So diagnosis and referral, the lipid management that includes atherogenic dyslipidemia, both pharmacologic and lifestyle, vascular management, that's the pro-thrombotic and pro-inflammatory states that oftentimes have hypertension as an underlying mechanism, as well as insulin resistance. But again, managing that hypertension, managing their sleep disorder, breathing if they have obstructive sleep apnea, battery liver disease, again, weight loss, nutrition, exercise, and then finally that insulin-resistant component, again, pharmacologic management, lifestyle. So oftentimes what these programs are are related to developing a risk assessment tool that looks for all of these areas, a number of labs, an entire workup, and then management based on the different comorbidities and what's been identified. As you bring it all together.

cardiometabolic disease

dyslipidemia

hypertension

insulin resistance

nutrition

exercise