COMMENTARY

What Cardiologists Should Know About Obesity

Moderator: Seth J. Baum, MD, FACC; Panelists: Caroline M. Apovian, MD; Scott Kahan, MD, MPH

Disclosures

November 08, 2018

Editorial Collaboration

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Seth J. Baum, MD: Welcome. I'm Dr Seth Baum, the immediate past president of the American Society for Preventive Cardiology ; a cardiologist and clinical lipidologist in Boca Raton, Florida ; and a professor at the Florida Atlantic University College of Medicine. I'm joined today by two superb doctors : Dr Scott Kahan of George Washington University and Dr Caroline Apovian of Boston University. Welcome.

Today we are going to be speaking about obesity in the cardiovascular patient.

As background, some numbers were released in 2016[1] that were horrific. We saw that overweight had increased to about 75% and obesity had increased to nearly 40% of adults in the United States, which is way up from 2013 and which is way up from the prior statistics. This is felt to cost the United States somewhere around $200 billion a year.[2] Just to give it a frame of reference, an obese patient costs an employer about $500 extra a year. This is a tremendous burden on our healthcare system and obviously a burden on individual patients because they have to deal with the morbidity issues associated with obesity.

[I would like to discuss] how we, as cardiologists, manage patients who suffer from obesity or overweight in the post-infarct state or perhaps post-revascularization condition . But prior to that, I would like to get both of your takes on two things that we hear a lot about. One is the obesity paradox and the other is the construct of the metabolically healthy obese patient. Dr Kahan, could you start with the obesity paradox?

Obesity Paradox

Scott Kahan, MD, MPH: The obesity paradox in this case refers to some earlier data[3,4,5,6,7] suggesting that people who are heavier may have a lower mortality risk from cardiovascular disease (CVD). It turns out that there is no obesity paradox, most likely ; rather, it is an issue with the methodology of the studies. It's a challenging thing to study.

When we look observationally, if people have chronic disease at the get-go, they tend to be thinner and have higher mortality risk. Once we remove that, there tends to be less of the obesity paradox. Moreover, if we consider, as the exposure, body mass index (BMI) or weight trajectory rather than a single weight in time in the past, and then try to associate that with CVD risk and mortality risk, again, the paradox even further goes away.

For the most part, this is a non-issue. Weight is an important risk factor. In virtually every patient who has excess weight, we want to make sure that they have support to help manage their weight and their health, in part to prevent CVD and CVD mortality.

Caroline M. Apovian, MD : When you look at obesity and mortality, there is a J-shaped curve, and it looks like there is a J-shaped curve for obesity, CVD, and mortality —but it's the middle part that is confusing. As Scott said, there are many confounding factors.[8]

Certainly, it is true that preventive effort (ie, keeping weight at a stable, normal range) will prevent a lot of CVD in the future, and people who maintain a certain level of cardiorespiratory fitness do prevent CVD. However, once obesity and, let's say, heart failure coexist, it looks as if it's true that obesity imparts a lower mortality rate,[7] but it may be because there are some confounders.

When you look at large sets of data and find that people with lower body weight have higher risk for mortality from their CVD, they may have had severe disease ongoing for a while that caused the weight loss. You see that with BMI and mortality in general.

I agree with Scott. I don't think that once you control for certain factors that there is an obesity paradox. It's just the way we look at data. Unfortunately, it can get very confusing, and sometimes people who are of low BMI are not cardiovascularly fit and do not have a lot of lean muscle mass (ie, sarcopenia), which can also lead to worse outcomes.

'Misclassification Problem' in Obesity

Baum: In cardiology, we have gotten in trouble a number of times in the past for confusing association and causation. It seems to me that nobody is going to do a clinical trial where you make some people obese and other people thin, and then put them through bypass to see how they do. All we have and all we will ever have is association. Is that fair?

When you think about the physiologic state of obesity, there's no biologic reason that I can think of that would confer a lower risk.

Apovian: Things might get better if we can figure out a better measure of body fat than the BMI. We can't do it yet because to get a really good measure of body fat, we have to do a dual-energy x-ray absorptiometry (DEXA) scan, which no one is going to do on thousands of people. If we could do the DEXA scan, I think we would find that those lean people who are fit (ie, have muscle mass) don't have a higher mortality with heart disease.

Baum: Are we ever going to get out of this mess? Do we have the capacity to get out of this? We are never going to be able to do a nice controlled outcomes trial. Isn't that correct?

Kahan: You are not going to be able to do a randomized controlled trial on this, but I don't think it's quite as dire as your thought-provoking question implies.

On the one hand, we have already teased apart a lot of this. As Caroline said, some of the problem comes from misclassification when you use BMI to identify initial risk. Some people who are heavy by way of BMI, but are fit and muscular, are misclassified and vice versa. A bigger issue, frankly, is people who are very thin. They look like they are a normal, healthy weight, but they are sarcopenic and osteopenic and have a high body fat, so they have a high risk.

Using better measures of exposure and classification minimizes this paradox. When we look at weight trajectory or multiple measures of weight and overweight as the exposures instead of using a single weight, BMI, or body fat percentage —or even a DEXA measure in the past as the exposure —this largely goes away. A big study published last year showed that.[9] Although it's not 100% the case, and we're not going to have randomized controlled trials, we're in less of a confusing situation than it seems.

On top of that, there is no biologic plausibility that I can think of whereby obesity would be protective in general. Maybe there are some nuance scenarios. You can make the argument that some people who are thin may be doing very unhealthy things to lose weight, but when you think about the physiologic state of obesity, there's no biologic reason that I can think of that would confer to a lower risk.

Taken together, these give us a pretty good sense of the risk for obesity and the limitations of the old theory of this obesity paradox. The challenge is that the media and other people are talking about it. People may believe this paradox because it's self-serving for their own reasons, but I think this is a health-communication thing more than an obesity-research thing.

Baum: That was very helpful. Both of you are saying that we should just stop talking about this. It's a misclassification problem and we should get it out of our minds.

'Metabolically Healthy' Obese Patient?

Baum: What about the issue of the metabolically healthy obese —a person who is obese and has normal triglyceride, HDL, blood pressure, and fasting blood sugar?

Those of us in the field do not think that there is really such a thing as metabolically healthy obesity.

Apovian: If we look at everyone in population studies with a BMI over 30 kg/m2 and break them down to those who have metabolic syndrome and those who don't have signs of metabolic syndrome, about one quarter of those people are supposedly metabolically healthy. Three quarters are going to have elements of metabolic syndrome: low HDL-C, elevated triglycerides, elevated waist circumference, elevated blood pressure, and elevated blood glucose. In that quarter, we think that obesity is going to catch up with them, certainly musculoskeletally. Obesity causes changes in the vasculature that lead to elevated left ventricular (LV) and diastolic dysfunction.

Those of us in the field do not think that there is really such a thing as metabolically healthy obesity. Perhaps we are looking at a slice on a timeline of people who have obesity and we are not waiting long enough to see that the obesity affects them in the future. We think it will.

Baum: In the world of obesity, it seems like you have the same problem that we in cardiology and lipidology have with statins. It's gotten into the lay press and it's all over the place that they cause your legs to fall off and they cause you to lose your memory and every other thing. We need to get that out of the discussion.

You have the same problem here with these two constructs. They should not even be a discussion point. Does that seem to be the case?

Apovian: It's a different scenario if you have a BMI of 40 kg/m2 and no comorbidities. Certainly, the patient with a BMI of 40 kg/m2 and metabolic syndrome is going to be at higher risk. There is no question about that, but it doesn't mean that the BMI of 40 kg/m2 with no comorbidities is metabolically healthy.

Kahan: I mostly agree; I'm just going to add a little nuance. I think this is a different situation than the obesity paradox situation, which is one of methodological challenges.

You can carry excess weight. In our society that is typical; our society drives gaining weight. But you can do healthy things. You can be active, eat healthful foods, and manage stress and have very positive CV risk factors. If that is the case, even if you're still somewhat overweight, it's perfectly fine to continue living your healthy life, even if there may be a risk 20 years down the line of some of these CV risk factors.

The issue for me more than anything is, again, a health-communications issue. A small percentage at any point in time have minimal metabolic health issues or no metabolic health issues we can find, despite having excess weight. Given that, it's often written up in newspaper articles, magazine articles, or elsewhere that obesity just does not matter and is not an issue —that it's not important to manage and it's only important to be active or the like. It's a paradoxical issue.

It's important for us to manage our weight and health behaviors. It's also important for us not to discount those who are doing lots of healthy behaviors but because of genetic and environmental reasons (ie , living in this obesogenic environment) they find it tough to maintain a BMI of 25 kg/m2, let alone a BMI of 22 kg/m2. There is some nuance here that is important for us to keep in mind.

Baum: You're not saying that if we see an obese patient who is otherwise living a healthy lifestyle and eating healthful foods, etc, that we should avoid encouraging that individual to lose weight, correct? It's still better to be an optimal weight?

Kahan: All else being equal, it's best to be at optimal weight, cholesterol level, blood pressure, etc. If all risk factors are normal and the patient just has excess weight, we call that stage 0 obesity. The goals for that patient probably are making sure that they don't gain more weight and making sure that they continue to do healthy things.

Would losing weight help a little bit? It very well may. But given that it's a challenging thing to do, and our example patient is doing very well and appears to be very cardiovascularly healthy, there is an argument to be made for not aggressively counseling for weight loss — rather, for informing the patient of the situation, supporting them so that they don't gain weight, and supporting them so that they continue their healthful behaviors and, hopefully, their healthful CV status.

Apovian: We have to talk about degrees. I agree with stage 0, but if that stage 0 is a BMI of 40 kg/m2, then recognize that that patient is still eligible for our most aggressive treatment, which is bariatric surgery. Patients with BMIs over 40 kg/m2, even with no comorbidities, may be eligible for surgery for their obesity, which would help them lose weight and, most important, keep that weight off.

Yes, obesity is a disease and we should not be criticizing patients who have obesity yet have a healthy lifestyle and are managing not to gain weight, but I still think you can't discount the BMI mortality curve. After a BMI of 25 kg/m2, it is true that mortality rate increases in both men and women.[10] You have to look at the body composition, but on a population basis, you still have to recognize that a higher BMI is going to give you a higher mortality rate.

Kahan: We can all agree that having a nuanced discussion about the different angles that this can take, and then using a shared decision-making process with the patient, is best for everyone all around.

Baum: This reminds me of the debate we have with familial hypercholesterolemia, the genetic disorder in individuals who are in their 40s or 50s who have no coronary disease, peripheral arterial disease, or carotid artery disease yet have an LDL cholesterol of 300 mg/dL. What do we do? It's an extreme example, but I certainly don't feel comfortable letting that person sit and wait. All things being equal, I'd rather treat that LDL.

Kahan: Is it fair to say that, although your clinical preference would be to treat the patient aggressively for cholesterol lowering, it would nonetheless be a process of informing the patient what the risks may be and what this challenging situation is . Ultimately, it's a shared decision-making process.

Baum: Everything is. I totally agree with you.

Managing the Obese Patient After a Cardiac Event

Baum: Let's talk about what we do for individuals who are obese and have gone through revascularization and are now in the process of going through rehab. How aggressive should we be?

Kahan: This is a challenging situation because, to my knowledge, there are no good data on whether we should be more aggressive with weight management treatment in the post–myocardial infarction (MI) setting. For patients with CVD who are back to their normal lives but have had an MI or equivalent in the past, we have lots of data showing that a number of our treatments for weight management can be quite helpful. By extension, we should not be scared of them like people may have been in the past.

For example, take bariatric surgery. We have very good data that it reduces mortality.[11] For [lorcaserin and liraglutide], which are US Food and Drug Administration (FDA)- approved for weight management, we have shown positive CV outcomes in patients with CVD or CVD equivalents.[12,13]

In another example, we have half of the Look AHEAD CV outcomes trial[14] showing benefit in an 8-year-long study of behavioral management for weight management. Although the bottom-line outcome was that losing a moderate amount of weight does not decrease CVD, when they lost at least 10%, there was a reduction in CVD mortality.

Post-MI is a challenging situation with limited data, but in people with CVD, we have shown good benefits with evidence-based treatments.

Baum: Caroline, do you agree that we are woefully undertreating or underserving this population?

Apovian: I definitely agree. If I were to look at where to intervene, I would try to continue from the point where the patient is discharged from rehab and get them to continue that program. I would love to see more coverage of cardiac rehab further out than the typical [duration]. Whatever the duration is, it's too short.

By the time I see them in my tertiary care center for obesity, they have gained weight post MI. I am then trying to get them back on a healthy diet and do physical activity. Whether or not I am able to add a medication to suppress their appetite, especially the ones that Scott mentioned —lorcaserin and liraglutide, which showed some CV benefit —depends on insurance coverage.

In patients who are eligible at that point for bariatric surgery, [I try to] get them to surgery so that they can reduce their mortality in the future. To date, of patients in the United States who are eligible for bariatric surgery, only 1% actually get that treatment.[15] Of patients who are eligible for our weight loss medications, only 2% get that treatment.[16] We are really undertreating obesity. Period.

Treating Obesity: Changing a Lasting-Legacy Effect and Improving Access

Baum: That is absolutely my sense in clinical practice. How do we change that? We are all terrified of obesity drugs because of the past history, although these new ones have entirely different mechanisms of action.

Apovian: There is a tipping point. We are at the point where many practitioners realize that obesity is a disease, but we have to communicate that effectively with education to the public and to the government and insurers. Scott has been working very diligently in the Washington, DC, area and I have been working hard through the Obesity Society to do that, but we still have a ways to go.

Baum: Yes, we do. What about the practitioner's fear of starting medications and lack of access to good bariatric surgery? These seem to be major problems.

Kahan: These are major problems. There is a legacy effect from some of the medications decades ago that had CV or other risks and were taken off the market. The newer generation of medications works by different mechanisms and is much better. It goes beyond that as well. In the late 1990s and in the first decade of the 2000s, the FDA changed their criteria quite significantly for approval both of diabetes and obesity medications. There are quite rigorous requirements for FDA approval of medications for both safety and efficacy. Medications that have been approved in the past decade have proven —using quite a large number of patients over long periods —to be relatively effective as well as safe. This legacy effect nonetheless limits use.

The other issue is access. You mentioned access to bariatric surgery; Caroline previously also mentioned access to medications. It's a big deal. Today, Medicare explicitly excludes medications for obesity from coverage. That is a legacy effect of obesity being classified as a cosmetic issue rather than a health condition, going back a decade and a half. We have a couple of bills in Congress that would reverse that explicit exclusion. We are making quite good progress on that. There is a good chance that if we have this panel in 2020, give or take, there will be a very different landscape. Medicare likely will no longer explicitly exclude medications. Private healthcare insurers will likely better cover medications.

It's slow, but we have been making a lot of progress in educating physicians, patients, and even third-party payers about obesity and obesity treatments. I think we'll continue to see improvements by way of all of those avenues.

Apovian: Along the same lines, at the government level we have been developing a new subspecialty in medicine called obesity medicine. Since 2013, we have an American Board of Obesity Medicine (ABOM) that gives a certifying exam. We have over 6000 doctors in the United States now certified to practice obesity medicine.

These doctors treat patients and educate patients, and educate their community of doctors, that obesity is a disease and should be treated just like hypertension and heart disease.

If someone has a BMI of 40 kg/m2, goes to surgery, and now their BMI is 22 kg/m2, the record usually shows that the obesity diagnosis is removed. But you would never do that in a patient who has hypertension and a normal blood pressure because they are on medications. That is one of these nuances. We are still not there. Obesity is a chronic relapsing condition that never goes away, even if your BMI is 22 kg/m2.

Baum: Of those 6000 people, how many are in the various specialties? How many cardiologists? Endocrinologists? Internists? Do you know that breakdown?

Kahan: I serve on the Board of Directors for ABOM. In general, the majority are primary care providers. There are quite a number of endocrinologists as well. There is a big dip after that. There are some, but not many, cardiologists. There are some bariatric surgeons, and so forth, but the vast majority are primary care as well as endocrinology.

Baum: We certainly need more of them, so keep up the great work, both of you.

Changing the Obesity 'Playing Field'

Baum: The 2013 guidelines[17] don't seem to have had the impact that we expected or wanted. What can we do to change this playing field so that we can effectively treat obese and overweight patients and turn the curve in the other direction so that in 2022, 50% of our population is overweight instead of 75%?

"I think that the next generation of young physicians is going to change the whole landscape [of obesity].

Kahan: Just putting out a very good guideline does not in itself do anything. Perhaps the more challenging piece is translation, communication, and implementation of those guidelines. That has been happening but, as you suggest, very slowly. There is more that we can do. We can speed up things like these types of panels and CMEs. Frankly, we are going to be trotting along for a little while.

Some of this will be a generational shift. We have shown some data[18] that when you look overall at the knowledge and clinical tendencies of healthcare providers with respect to obesity and obesity treatments, it's quite pitiful. There is a difference between those who are relatively recently out of training and those who are out of training for quite a long time.

As we incorporate more training into medical school, residency training, and even fellowship training, I think that the next generation of young physicians is going to change the whole landscape. Hopefully we can make more progress with those that are already in practice.

Apovian: I believe that the only way to really push this movement forward is to continue to press on medical schools to add more education on obesity. Everything will follow from 20 years of research finding that obesity is a disease. Students need to learn the pathophysiology of obesity, and we think we know that. We may learn in the future that there is more to it than even the complex pathways that we now have discovered. Students need to grow into their residency realizing that it's a disease. That will reduce the stigma on the part of the provider, inform treatment, and ensure that obesity will be treated just like any other disease. I think we are starting to move along on that path.

Baum: That is encouraging. I want to thank you both for being here and for speaking about obesity and therapeutics for obesity. I really appreciate everything you are doing to advance this field.

Apovian: Thank you, Seth. It has been great talking to you and Scott.

Baum: It's been fun.

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